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- Malmgren, B, et al.
(author)
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Abnormalities in Tooth Formation after Early Bisphosphonate Treatment in Children with Osteogenesis Imperfecta
- 2021
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In: Calcified tissue international. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 109:2, s. 121-131
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Journal article (peer-reviewed)abstract
- Treatment with intravenous bisphosphonate (BP) in children and adolescents with osteogenesis imperfecta (OI) started in Sweden in 1991. No human studies on the role of BP therapy in development of disturbances in tooth mineralization or tooth morphology have been published. The study cohort comprised 219 individuals who were divided into four groups: group 1, BP treatment onset before 2 years of age (n = 22); group 2, BP treatment onset between 2 and 6 years of age (n = 20); group 3, BP treatment onset between 6 and 10 years of age (n = 13); and a control group of patients with OI who had not received BP therapy (n = 164). The chi-square test was used in between-group comparisons of the prevalence of tooth agenesis. The prevalence of tooth agenesis was significantly higher in children who began BP treatment before the age of 2 years (group 1; 59%,) compared to the controls (10%; p < 0.001) and to children who had begun BP therapy between ages 2 and 6 years (group 2; 10%; p = 0.009) or between ages 6 and 10 years (group 3; 8%; p = 0.003). Different types of disturbances in the enamel formation were seen in 52 premolars, where 51 were seen in those who began BP treatment before the age of 2 years. To conclude, starting BP treatment before the age of 2 years increases the risk of abnormalities in tooth formation manifesting as morphological aberrations, tooth agenesis, and enamel defects.
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- Malmgren, B, et al.
(author)
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Bisphosphonate Therapy and Tooth Development in Children and Adolescents with Osteogenesis Imperfecta
- 2020
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In: Calcified tissue international. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 107:2, s. 143-150
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Journal article (peer-reviewed)abstract
- Osteogenesis imperfecta (OI) is a heterogeneous connective tissue disorder characterized by repeated fractures and skeletal disorders. At present, bisphosphonate (BP) therapy is the gold standard for OI treatment. The present retrospective study evaluated the effect of BP therapy on tooth development and eruption of permanent teeth in a cohort of children receiving pamidronate. Three groups were studied: patients with OI who were treated with BPs (n = 45), patients with OI who were not treated with BPs (n = 117), and age- and gender-matched healthy controls (n = 121). Dental age, dental maturity, and tooth eruption were assessed on panoramic radiographs using the methods of Demirjian et al. (Hum Biol 45(2):211–227, 1973) and Haavikko (Suom Hammaslaak Toim 66(3):103–170, 1970) and were evaluated using the t-test, Chi-square test, and the Mann–Whitney U test. Dental age in the study group was significantly (p < 0.05) lower than chronological age compared with both control groups. Dental maturity and the eruption of permanent teeth were also significantly (p < 0.05) delayed in the study group in relation to the two control groups. The dental age was significantly lower (p < 0.001) in patients with OI type III treated with BPs compared with healthy controls and the dental maturation was significantly delayed in patients with OI type IV treated with BPs compared with those not treated. In conclusion, BP therapy in OI patients seems to lower the dental age, delay the dental maturity, and tooth eruption. BP administration before 2 years of age might be a contributing factor.
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- Malmgren, B., et al.
(author)
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Tooth agenesis in osteogenesis imperfecta related to mutations in the collagen type I genes
- 2017
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In: Oral Diseases. - : Wiley. - 1354-523X .- 1601-0825. ; 23:1, s. 42-49
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Journal article (peer-reviewed)abstract
- BackgroundOsteogenesis imperfecta (OI) is a heterogeneous group of disorders of connective tissue, mainly caused by mutations in the collagen type I genes (COL1A1 and COL1A2). Tooth agenesis is a common feature of OI. We investigated the association between tooth agenesis and collagen type I mutations in individuals with OI. Subjects and methodsIn this cohort study, 128 unrelated individuals with OI were included. Panoramic radiographs were analyzed regarding dentinogenesis imperfecta (DGI) and congenitally missing teeth. The collagen I genes were sequenced in all individuals, and in 25, multiplex ligation-dependent probe amplification was performed. ResultsMutations in the COL1A1 and COL1A2 genes were found in 104 of 128 individuals. Tooth agenesis was diagnosed in 17% (hypodontia 11%, oligodontia 6%) and was more frequent in those with DGI (P=0.016), and in those with OI type III, 47%, compared to those with OI types I, 12% (P=0.003), and IV, 13% (P=0.017). Seventy-five percent of the individuals with oligodontia (6 missing teeth) had qualitative mutations, but there was no association with OI type, gender, or presence of DGI. ConclusionThe prevalence of tooth agenesis is high (17%) in individuals with OI, and OI caused by a qualitative collagen I mutation is associated with oligodontia.
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- Ahlström, Aisling, 1976, et al.
(author)
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A double-blind randomized controlled trial investigating a time-lapse algorithm for selecting Day 5 blastocysts for transfer
- 2022
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In: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 37:4, s. 708-717
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Journal article (peer-reviewed)abstract
- STUDY QUESTION Can use of a commercially available time-lapse algorithm for Day 5 blastocyst selection improve pregnancy rates compared with morphology alone? SUMMARY ANSWER The use of a time-lapse selection model to choose blastocysts for fresh single embryo transfer on Day 5 did not improve ongoing pregnancy rate compared to morphology alone. WHAT IS KNOWN ALREADY Evidence from time-lapse monitoring suggests correlations between timing of key developmental events and embryo viability. No good quality evidence exists to support improved pregnancy rates following time-lapse selection. STUDY DESIGN, SIZE, DURATION A prospective multicenter randomized controlled trial including 776 randomized patients was performed between 2018 and 2021. Patients with at least two good quality blastocysts on Day 5 were allocated by a computer randomization program in a proportion of 1:1 into either the control group, whereby single blastocysts were selected for transfer by morphology alone, or the intervention group whereby final selection was decided by a commercially available time-lapse model. The embryologists at the time of blastocyst morphological scoring were blinded to which study group the patients would be randomized, and the physician and patients were blind to which group they were allocated until after the primary outcome was known. The primary outcome was number of ongoing pregnancies in the two groups. PARTICIPANTS/MATERIALS, SETTING, METHODS From 10 Nordic IVF clinics, 776 patients with a minimum of two good quality blastocysts on Day 5 (D5) were randomized into one of the two study groups. A commercial time-lapse model decided the final selection of blastocysts for 387 patients in the intervention (time-lapse) group, and blastocysts with the highest morphological score were transferred for 389 patients in the control group. Only single embryo transfers in fresh cycles were performed. MAIN RESULTS AND THE ROLE OF CHANCE In the full analysis set, the ongoing pregnancy rate for the time-lapse group was 47.4% (175/369) and 48.1% (181/376) in the control group. No statistically significant difference was found between the two groups: mean difference -0.7% (95% CI -8.2, 6.7, P = 0.90). Pregnancy rate (60.2% versus 59.0%, mean difference 1.1%, 95% CI -6.2, 8.4, P = 0.81) and early pregnancy loss (21.2% versus 18.5%, mean difference 2.7%, 95% CI -5.2, 10.6, P = 0.55) were the same for the time-lapse and the control group. Subgroup analyses showed that patient and treatment characteristics did not significantly affect the commercial time-lapse model D5 performance. In the time-lapse group, the choice of best blastocyst changed on 42% of occasions (154/369, 95% CI 36.9, 47.2) after the algorithm was applied, and this rate was similar for most treatment clinics. LIMITATIONS, REASONS FOR CAUTION During 2020, the patient recruitment rate slowed down at participating clinics owing to coronavirus disease-19 restrictions, so the target sample size was not achieved as planned and it was decided to stop the trial prematurely. The study only investigated embryo selection at the blastocyst stage on D5 in fresh IVF transfer cycles. In addition, only blastocysts of good morphological quality were considered for transfer, limiting the number of embryos for selection in both groups: also, it could be argued that this manual preselection of blastocysts limits the theoretical selection power of time-lapse, as well as restricting the results mainly to a good prognosis patient group. Most patients were aimed for blastocyst stage transfer when a minimum of five zygotes were available for extended culture. Finally, the primary clinical outcome evaluated was pregnancy to only 6-8 weeks. WIDER IMPLICATIONS OF THE FINDINGS The study suggests that time-lapse selection with a commercially available time-lapse model does not increase chance of ongoing pregnancy after single blastocyst transfer on Day 5 compared to morphology alone. STUDY FUNDING/COMPETING INTEREST(S) The study was financed by a grant from the Swedish state under the ALF-agreement between the Swedish government and the county councils (ALFGBG-723141). Vitrolife supported the study with embryo culture dishes and culture media. During the study period, T.H. changed his employment from Livio AB to Vitrolife AB. All other authors have no conflicts of interests to disclose. DATE OF FIRST PATIENT'S ENROLMENT 11 June 2018.
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- Batstone, K., et al.
(author)
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Robust Self-calibration of Constant Offset Time-difference-of-arrival
- 2019
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In: 2019 IEEE International Conference on Acoustics, Speech, and Signal Processing, ICASSP 2019 - Proceedings. - 9781479981311 ; 2019-May, s. 4410-4414
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Conference paper (peer-reviewed)abstract
- In this paper we study the problem of estimating receiver and sender positions from time-difference-of-arrival measurements, assuming an unknown constant time-difference-of-arrival offset. This problem is relevant for example for repetitive sound events. In this paper it is shown that there are three minimal cases to the problem. One of these (the five receiver, five sender problem) is of particular importance. A fast solver (with run-time under 4 μs) is given. We show how this solver can be used in robust estimation algorithms, based on RANSAC, for obtaining an initial estimate followed by local optimization using a robust error norm. The system is verified on both real and synthetic data.
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- Ciray, I., et al.
(author)
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Effect of granulocyte colony-stimulating factor (G-CSF)-supported chemotherapy on MR imaging of normal red bone marrow in breast cancer patients with focal bone metastases
- 2003
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In: Acta Radiol. - 0284-1851 .- 1600-0455. ; 44:5, s. 472-84
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Journal article (peer-reviewed)abstract
- PURPOSE: To investigate the effect of granulocyte colony-stimulating factor (G-CSF)-supported chemotherapy on normal red bone marrow MR imaging in breast cancer patients with focal bone metastases. MATERIAL AND METHODS: Fifteen breast cancer patients who were examined before and after chemotherapy with T1-weighted-SE and long echo-time inversion-recovery turbo-spin-echo (long TE IR-TSE) sequences in the thoracolumbar spine and pelvis were retrospectively studied. Nine of them received G-CSF therapy after the administration of each chemotherapy course. Of these 9 patients, the MR follow-ups were performed during G-CSF in 4 patients and after G-CSF therapy in 5 patients. Six patients did not receive G-CSF. Signal intensity (SI) changes in normal bone marrow were evaluated visually in all patients and quantitatively in 13 patients. RESULTS: In all 4 patients investigated during G-CSF therapy a diffuse, homogeneous SI increase on long TE IR-TSE was observed visually and quantitatively in initially normal bone marrow. This change obscured some focal lesions in 2 patients. No such SI change was visible after G-CSF therapy (p = 0.008) or in patients not receiving G-CSF. On T1-weighted images an SI decrease was found both during and after G-CSF therapy, but an increase occurred in patients not receiving G-CSF. CONCLUSION: G-CSF-supported chemotherapy can induce diffuse SI changes in normal red bone marrow on MR imaging. On long TE IR-TSE, the changes are visible during G-CSF treatment and can lead to misinterpretations in the response evaluation of bone metastases to therapy.
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- Ehrlund, A, et al.
(author)
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Transcriptional Dynamics During Human Adipogenesis and Its Link to Adipose Morphology and Distribution
- 2017
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In: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 66:1, s. 218-230
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Journal article (peer-reviewed)abstract
- White adipose tissue (WAT) can develop into several phenotypes with different pathophysiological impact on type 2 diabetes. To better understand the adipogenic process, the transcriptional events that occur during in vitro differentiation of human adipocytes were investigated and the findings linked to WAT phenotypes. Single-molecule transcriptional profiling provided a detailed map of the expressional changes of genes, enhancers, and long noncoding RNAs, where different types of transcripts share common dynamics during differentiation. Common signatures include early downregulated, transient, and late induced transcripts, all of which are linked to distinct developmental processes during adipogenesis. Enhancers expressed during adipogenesis overlap significantly with genetic variants associated with WAT distribution. Transiently expressed and late induced genes are associated with hypertrophic WAT (few but large fat cells), a phenotype closely linked to insulin resistance and type 2 diabetes. Transcription factors that are expressed early or transiently affect differentiation and adipocyte function and are controlled by several well-known upstream regulators such as glucocorticosteroids, insulin, cAMP, and thyroid hormones. Taken together, our results suggest a complex but highly coordinated regulation of adipogenesis.
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- Johansson, Karl H., et al.
(author)
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Multivariable controller tuning
- 1998
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In: Proceedings of the American Control Conference, 1998. - : IEEE. - 0780345304 ; , s. 3514-3518
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Conference paper (peer-reviewed)abstract
- The problem of tuning individual loops in a multivariable controller is investigated. It is shown how the performance of a specific loop relates to a row in the controller matrix. Several interpretations of this relation are given. An algorithm is also presented that estimates the model required for the tuning via a relay feedback experiment. The algorithm does not need any prior information about the system or the controller. The results are illustrated by an example.
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- Larsson, M., et al.
(author)
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Upgrade Methods for Stratified Sensor Network Self-Calibration
- 2020
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In: 2020 IEEE International Conference on Acoustics, Speech, and Signal Processing, ICASSP 2020 - Proceedings. - 1520-6149. - 9781509066315 ; 2020-May, s. 4851-4855
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Conference paper (peer-reviewed)abstract
- Estimating receiver and sender positions is often solved using a stratified, two-tiered approach. In the first step the problem is converted to a low-rank matrix estimation problem. The second step can be seen as an affine upgrade. This affine upgrade is the focus of this paper. In the paper new efficient algorithms for solving for the upgrade parameters using minimal data are presented. It is also shown how to combine such solvers as initial estimates, either directly or after a hypothesis and test step, in optimization of likelihood. The system is verified on both real and synthetic data.
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