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- Arvidsson, Ida, et al.
(författare)
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Comparing a pre-defined versus deep learning approach for extracting brain atrophy patterns to predict cognitive decline due to Alzheimer’s disease in patients with mild cognitive symptoms
- 2024
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Ingår i: Alzheimer's Research and Therapy. - 1758-9193. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Predicting future Alzheimer’s disease (AD)-related cognitive decline among individuals with subjective cognitive decline (SCD) or mild cognitive impairment (MCI) is an important task for healthcare. Structural brain imaging as measured by magnetic resonance imaging (MRI) could potentially contribute when making such predictions. It is unclear if the predictive performance of MRI can be improved using entire brain images in deep learning (DL) models compared to using pre-defined brain regions. Methods: A cohort of 332 individuals with SCD/MCI were included from the Swedish BioFINDER-1 study. The goal was to predict longitudinal SCD/MCI-to-AD dementia progression and change in Mini-Mental State Examination (MMSE) over four years. Four models were evaluated using different predictors: (1) clinical data only, including demographics, cognitive tests and APOE ε4 status, (2) clinical data plus hippocampal volume, (3) clinical data plus all regional MRI gray matter volumes (N = 68) extracted using FreeSurfer software, (4) a DL model trained using multi-task learning with MRI images, Jacobian determinant images and baseline cognition as input. A double cross-validation scheme, with five test folds and for each of those ten validation folds, was used. External evaluation was performed on part of the ADNI dataset, including 108 patients. Mann-Whitney U-test was used to determine statistically significant differences in performance, with p-values less than 0.05 considered significant. Results: In the BioFINDER cohort, 109 patients (33%) progressed to AD dementia. The performance of the clinical data model for prediction of progression to AD dementia was area under the curve (AUC) = 0.85 and four-year cognitive decline was R2 = 0.14. The performance was improved for both outcomes when adding hippocampal volume (AUC = 0.86, R2 = 0.16). Adding FreeSurfer brain regions improved prediction of four-year cognitive decline but not progression to AD (AUC = 0.83, R2 = 0.17), while the DL model worsened the performance for both outcomes (AUC = 0.84, R2 = 0.08). A sensitivity analysis showed that the Jacobian determinant image was more informative than the MRI image, but that performance was maximized when both were included. In the external evaluation cohort from ADNI, 23 patients (21%) progressed to AD dementia. The results for predicted progression to AD dementia were similar to the results for the BioFINDER test data, while the performance for the cognitive decline was deteriorated. Conclusions: The DL model did not significantly improve the prediction of clinical disease progression in AD, compared to regression models with a single pre-defined brain region.
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- Jangsten, Elisabeth, 1954, et al.
(författare)
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A comparison of active management and expectant management of the third stage of labour: a Swedish randomised controlled trial.
- 2011
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Ingår i: BJOG : an international journal of obstetrics and gynaecology. - : Wiley. - 1471-0528 .- 1470-0328. ; 118:3, s. 362-9
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Tidskriftsartikel (refereegranskat)abstract
- Please cite this paper as: Jangsten E, Mattsson L, Lyckestam I, Hellström A, Berg M. A comparison of active management and expectant management of the third stage of labour: a Swedish randomised controlled trial. BJOG 2011;118:362-369. Objective To compare blood loss in women actively and expectantly managed in the third stage of labour. Design Randomised controlled trial (RCT). Setting Two delivery units at a Swedish university hospital. Population Healthy women with normal pregnancies, at gestational age 34-43weeks, with singleton cephalic presentation and expected vaginal delivery. Methods The women were randomly allocated to either active (n=903) or expectant (n=899) management of the third stage of labour. Main outcome measures The primary outcome was blood loss>1000ml, and secondary outcomes were mean blood loss, duration of third stage, retained placenta, haemoglobin level and blood transfusion. Results Blood loss>1000ml occurred in 10% of the actively managed group and 16.8% of the expectantly managed group (P<0.001). Mean blood loss was 535ml in the actively managed group and 680ml in the expectantly managed group (P<0.001). A prolonged duration of the third stage was associated with increased blood loss. Increased placenta weight was associated with increased blood loss. The haemoglobin level was 118g/dl in actively managed women and 115g/dl in expectantly managed women (P<0.001) the day after childbirth. The occurrence of retained placenta and the number of blood transfusions did not differ between the groups. Conclusions Active management of the third stage of labour was associated with less blood loss compared with expectant management. It is reasonable to advocate this regime, especially in primiparous women.
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- Joshi, Peter K, et al.
(författare)
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Directional dominance on stature and cognition in diverse human populations
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462
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Tidskriftsartikel (refereegranskat)abstract
- Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
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- Karlsson, Linda, et al.
(författare)
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Cerebrospinal fluid reference proteins increase accuracy and interpretability of biomarkers for brain diseases.
- 2024
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Ingår i: Nature Communications. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Cerebrospinal fluid (CSF) biomarkers reflect brain pathophysiology and are used extensively in translational research as well as in clinical practice for diagnosis of neurological diseases, e.g., Alzheimer's disease (AD). However, CSF biomarker concentrations may be influenced by non-disease related inter-individual variability. Here we use a data-driven approach to demonstrate the existence of inter-individual variability in mean standardized CSF protein levels. We show that these non-disease related differences cause many commonly reported CSF biomarkers to be highly correlated, thereby producing misleading results if not accounted for. To adjust for this inter-individual variability, we identified and evaluated high-performing reference proteins which improved the diagnostic accuracy of key CSF AD biomarkers. Our reference protein method attenuates the risk for false positive findings, and improves the sensitivity and specificity of CSF biomarkers, with broad implications for both research and clinical practice.
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- Kater, Arnon P., et al.
(författare)
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Minimal residual disease-guided stop and start of venetoclax plus ibrutinib for patients with relapsed or refractory chronic lymphocytic leukaemia (HOVON141/VISION) : primary analysis of an open-label, randomised, phase 2 trial
- 2022
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Ingår i: The Lancet Oncology. - : ELSEVIER SCIENCE INC. - 1470-2045 .- 1474-5488. ; 23:6, s. 818-828
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Tidskriftsartikel (refereegranskat)abstract
- Background Targeted time-limited treatment options are needed for patients with relapsed or refractory chronic lymphocytic leukaemia. The aim of this study was to investigate the efficacy of minimal residual disease (MRD)-guided, time-limited ibrutinib plus venetoclax treatment in this patient group. Methods HOVON141/VISION was an open-label, randomised, phase 2 trial conducted in 47 hospitals in Belgium, Denmark, Finland, the Netherlands, Norway, and Sweden. Eligible participants were aged 18 years or older with previously treated chronic lymphocytic leukaemia with or without TP53 aberrations; had not been exposed to Bruton tyrosine-kinase inhibitors or BCL2 inhibitors; had a creatinine clearance rate of 30 mL/min or more; and required treatment according to International Workshop on Chronic Lymphocytic Leukemia 2018 criteria. Participants with undetectable MRD (< 10(-4); less than one chronic lymphocytic leukaemia cell per 10 000 leukocytes) in peripheral blood and bone marrow after 15 28-day cycles of oral ibrutinib (420 mg once daily) plus oral venetoclax (weekly ramp-up 20 mg, 50 mg, 100 mg, 200 mg, up to 400 mg once daily) were randomly assigned (1:2) to ibrutinib maintenance or treatment cessation. Patients who were MRD positive continued to receive ibrutinib monotherapy. Patients who became MRD (> 10(-2)) during observation reinitiated treatment with ibrutinib plus venetoclax. The primary endpoint was progression-free survival at 12 months after random assignment in the treatment cessation group. Progression-free survival was analysed in the intention-to-treat population. All patients who received at least one dose of study drug were included in the safety assessment. The study is registered at ClinicalTrials.gov, NCT03226301, and is active but not recruiting. Findings Between July 12, 2017, and Jan 21, 2019, 230 patients were enrolled, 225 of whom were eligible. 188 (84%) of 225 completed treatment with ibrutinib plus venetoclax and were tested for MRD at cycle 15. After cycle 15, 78 (35%) patients had undetectable MRD and 72 (32%) were randomly assigned to a treatment group (24 to ibrutinib maintenance and 48 to treatment cessation). The remaining 153 patients were not randomly assigned and continued with ibrutinib monotherapy. Median follow-up of 208 patients still alive and not lost to follow-up at data cutoff on June 22, 2021, was 34middot4 months (IQR 30.6-37.9). Progression-free survival after 12 months in the treatment cessation group was 98% (95% CI 89-100). Infections (in 130 [58%] of 225 patients), neutropenia (in 91 [40%] patients), and gastrointestinal adverse events (in 53 [24%] patients) were the most frequently reported; no new safety signals were detected. Serious adverse events were reported in 46 (40%) of 116 patients who were not randomly assigned and who continued ibrutinib maintenance after cycle 15, eight (33%) of 24 patients in the ibrutinib maintenance group, and four (8%) of 48 patients in the treatment cessation group. One patient who was not randomly assigned had a fatal adverse event (bleeding) deemed possibly related to ibrutinib. Interpretation These data point to a favourable benefit-risk profile of MRD-guided, time-limited treatment with ibrutinib plus venetoclax for patients with relapsed or refractory chronic lymphocytic leukaemia, suggesting that MRD-guided cessation and reinitiation is feasible in this patient population. Copyright (C) 2022 Elsevier Ltd. All rights reserved.
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- Kristoffersson, Ida, 1980-, et al.
(författare)
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Framtidsscenarier för självkörande fordon på väg : samhällseffekter 2030 med utblick mot 2050
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Utvecklingen inom tekniken för självkörande fordon går snabbt och många fordonstillverkare (GM, Ford, Toyota, BMW, Audi, VW med flera) anger att de kommer lansera ett fullt ut självkörande fordon på marknaden kring år 2020. Även om teknikutvecklingen har gått och kommer gå snabbt de närmaste åren finns stora frågetecken kvar kring hur de självkörande fordonen kommer tas emot av samhället, var de kommer få köra, om de kommer användas främst som privata eller delade fordon, hur trafik-, integritets- och cyber-säkra de kommer vara och upplevas som av användarna, och i vilken utsträckning de kommer påverka accepterad pendlingstid, färdmedelsval och inducerat bilresande.Samtidigt påverkas de långsiktiga samhällsnyttorna med självkörande fordon inte främst av teknologiska framsteg utan mestadels av vilken roll de självkörande fordonen kommer få i vårt samhälle, det vill säga vilka effekter de får på trafiksystemet och samhällsplaneringen i stort. Det är därför viktigt att tidigt uppskatta möjliga framtidsscenarier för självkörande fordon. Utifrån dessa scenarier kan man sedan föra en diskussion kring hur regler och styrmedel bör användas för att största möjliga samhällsnytta ska uppnås.Detta notat beskriver det arbete med framtidsscenarier för självkörande fordon som gjorts under vintern 2016/2017. En analysgrupp på fem personer har, med stöd av en expertgrupp för persontransporter som samlats för tre heldagsworkshops, arbetat fram både en säker utveckling mot 2030 och två osäkra axlar som lett fram till fyra möjliga scenarier för framtiden med självkörande fordon i Sverige. Med medverkan från 40 experter från 23 organisationer inom transportområdet är denna studie unik jämfört med tidigare scenario-arbeten kring utvecklingen för självkörande fordon, vilka byggt antingen på litteraturstudier eller expertworkshops med ett fåtal forskare.
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- Mattsson, Kristina, et al.
(författare)
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Maternal smoking during pregnancy and offspring type 1 diabetes mellitus risk: accounting for HLA haplotype.
- 2015
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 1573-7284 .- 0393-2990. ; 30:3, s. 231-238
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Tidskriftsartikel (refereegranskat)abstract
- The main objective of this study was to investigate the risk of type 1 diabetes mellitus (T1D) in children exposed to tobacco smoking in utero, also taking genetic predisposition as expressed by HLA haplotype into account. In Skåne, the southernmost county of Sweden, all children born 1999-2005 who developed T1D were registered, resulting in 344 cases. For each child with T1D, three control children, matched for HLA haplotype and birthyear, were selected. Information on prenatal smoking exposure was retrieved from a regional birth register. Conditional logistic regressions were used to evaluate T1D risk following prenatal smoking exposure. In these data, maternal smoking in early pregnancy was associated with a higher risk of her child developing T1D [odds ratio (OR) 2.83; 95 % confidence interval (CI) 1.67-4.80 for 1-9 cigarettes/day, and OR 3.91; 95 % CI 1.22-12.51 for >9 cigarettes/day]. Results remained through all adjustments and sensitivity analyses. When genetic predisposition in terms of HLA haplotype was taken into account, we found that children exposed to smoking during fetal life were at higher risk of developing T1D in childhood.
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