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- Dahl, F, et al.
(author)
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Imaging single DNA molecules for high precision NIPT
- 2018
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 4549-
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Journal article (peer-reviewed)abstract
- Cell-free DNA analysis is becoming adopted for first line aneuploidy screening, however for most healthcare programs, cost and workflow complexity is limiting adoption of the test. We report a novel cost effective method, the Vanadis NIPT assay, designed for high precision digitally-enabled measurement of chromosomal aneuploidies in maternal plasma. Reducing NIPT assay complexity is achieved by using novel molecular probe technology that specifically label target chromosomes combined with a new readout format using a nanofilter to enrich single molecules for imaging and counting without DNA amplification, microarrays or sequencing. The primary objective of this study was to assess the Vanadis NIPT assay with respect to analytical precision and clinical feasibility. Analysis of reference DNA samples indicate that samples which are challenging to analyze with low fetal-fraction can be readily detected with a limit of detection determined at <2% fetal-fraction. In total of 286 clinical samples were analysed and 30 out of 30 pregnancies affected by trisomy 21 were classified correctly. This method has the potential to make cost effective NIPT more widely available with more women benefiting from superior detection and false positive rates.
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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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- Astrom, M., et al.
(author)
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Population health status based on the EQ-5D-Y-3L among adolescents in Sweden: Results by sociodemographic factors and self-reported comorbidity
- 2018
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In: Quality of Life Research. - : Springer Science and Business Media LLC. - 0962-9343 .- 1573-2649. ; 27:11, s. 2859-2871
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Journal article (peer-reviewed)abstract
- PurposeThe EQ-5D-Y-3L is a generic health-related quality of life (HRQoL) measure developed for youth from 8years old. The aim of this study is to present population health status, based on the EQ-5D-Y-3L, among adolescents in Sweden, by sex, age, self-reported comorbidity and parents' occupational status.MethodsData were obtained from a cross-sectional total survey among students, aged 13-18 years, in a Swedish County year 2014. The survey included EQ-5D-Y-3L, questions regarding self-reported health, disease, functional impairment and mental distress. Parents' occupational status was used as a proxy for socio-economic status.ResultsA total of 6574 participants answered all the EQ-5D-Y-3L dimensions (mean age was 15.9years, same proportion of boys and girls). Girls reported more problems than boys in the dimensions doing usual activities', having pain or discomfort' and feeling worried, sad or unhappy', and lower mean VAS score. Respondents with one or both parents unemployed reported more problems with usual activities, pain/discomfort and in the mood dimension than those with both parents employed. Those with comorbidity had in general more problems in all dimensions and lower mean VAS score. The highest impact on VAS score was found for adolescents who reported that they always felt depressed.ConclusionsSex, age, self-reported comorbidity and parents' occupational status were associated with HRQoL determined by the EQ-5D-Y-3L in the general population of adolescents. The ability of EQ-5D-Y-3L to distinguish adolescents' health status based on these factors confirms the instrument's usefulness in assessment of HRQoL and as guidance for prioritization.
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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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- Juliusson, Gunnar, et al.
(author)
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Attitude towards remission induction for elderly patients with acute myeloid leukemia influences survival.
- 2006
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In: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 20:1, s. 42-47
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Journal article (peer-reviewed)abstract
- Combination chemotherapy may induce remission from acute myeloid leukemia (AML), but validated criteria for treatment of elderly are lacking. The remission intention ( RI) rate for elderly patients, as reported to the Swedish Leukemia Registry, was known to be different when comparing the six health care regions, but the consequences of different management are unknown. The Leukemia Registry, containing 1672 AML patients diagnosed between 1997 and 2001, with 98% coverage and a median follow-up of 4 years, was completed with data from the compulsory cancer and population registries. Among 506 treated and untreated patients aged 70-79 years with AML (non-APL), there was a direct correlation between the RI rate in each health region ( range 36-76%) and the two-year overall survival, with no censored observations (6-21%) ( v 2 for trend = 11.3, P < 0.001; r(2) = 0.86, P < 0.02, nonparametric). A 1-month landmark analysis showed significantly better survival in regions with higher RI rates ( P = 0.003). Differences could not be explained by demographics, and was found in both de novo and secondary leukemias. The 5-year survival of the overall population aged 70-79 years was similar between the regions. Survival of 70-79-year-old AML patients is better in regions where more elderly patients are judged eligible for remission induction.
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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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- Astrom, M., et al.
(author)
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EQ-5D-Y-5L as a patient-reported outcome measure in psychiatric inpatient care for children and adolescents - a cross-sectional study
- 2020
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In: Health and Quality of Life Outcomes. - : Springer Science and Business Media LLC. - 1477-7525. ; 18:1
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Journal article (peer-reviewed)abstract
- Background Psychiatric disorders have a major individual and societal impact. Until now, the association between health-related quality of life and physical disorders has been far more investigated than the association with psychiatric disorders. Patient-reported outcome measures makes it possible to capture the patient perspective to improve treatments and evaluate treatment outcomes. The aim of this study is to measure health-related quality of life with the EQ-5D-Y-5L among patients in child and adolescent psychiatric inpatient care and to test the instrument's psychometric properties in terms of feasibility and construct validity. Methods Data were collected at the child and adolescent psychiatric inpatient facility in Region Stockholm. A questionnaire including the EQ-5D-Y-5L instrument, the Strengths and Difficulties Questionnaire with an impact supplement and a self-rated health question, was administered for self-completion using paper and pencil, with an interviewer present. The Chi-square test was used to investigate differences in proportion of reported problems in the EQ-5D-Y-5L dimensions and the Mann-Whitney U test was used for differences in mean EQ VAS scores. Feasibility was assessed by investigating proportion of missing and ambiguous answers and Spearman's and Pearson's correlation were used to examine construct validity. Results In total 52 adolescents participated in the study and the majority were girls. The most common diagnosis at admission was depressive episode/recurrent depressive disorder. All participants reported problems on at least one dimension. Most problems were reported in the dimension 'feeling worried, sad or unhappy', where 64% reported severe or extreme problems. Mean EQ VAS score was 29.2. Feasibility was supported and construct validity indicated as some of the hypothesised correlations between the EQ-5D-Y-5 L and the Strengths and Difficulties Questionnaire were found, however, for 'doing usual activities' and 'having pain or discomfort' the correlations were weaker than hypothesised. Conclusions This is the first study where the newly developed EQ-5D-Y-5L instrument has been used in psychiatric inpatient care for youth. Participants reported problems in all severity levels in most of the EQ-5D-Y-5L dimensions; mean EQ VAS score was considerably low. Feasibility of the EQ-5D-Y-5L was supported, however other psychometric properties need to be further tested in a larger sample.
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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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