| 51. |
- Delcoigne, B, et al.
(författare)
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Exposure to specific tumour necrosis factor inhibitors and risk of demyelinating and inflammatory neuropathy in cohorts of patients with inflammatory arthritis: a collaborative observational study across five Nordic rheumatology registers
- 2023
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Ingår i: RMD open. - : BMJ. - 2056-5933. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- To compare incidences of neuroinflammatory events, including demyelinating disease (DML), inflammatory polyneuropathies (IPN) and multiple sclerosis (MS), in patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA; including psoriatic arthritis) starting a tumour necrosis factor inhibitor (TNFi), investigating whether monoclonal TNFi antibodies (other TNFis (oTNFis)) confer higher risk than etanercept.MethodsThis is an observational cohort study including patients from the five Nordic countries starting a TNFi in 2001–2020. Time to first neuroinflammatory event was identified through register linkages. We calculated crude incidence rates (cIR) per 1000 person-years and used multivariable-adjusted Cox regression to compare incidences of neuroinflammatory events overall and for DML, IPN and MS with oTNFi versus etanercept. We further examined individual TNFis and indications.Results33 883 patients with RA and 28 772 patients with SpA were included, initiating 52 704 and 46 572 treatment courses, respectively. In RA, we observed 135 neuroinflammatory events (65% DML) with cIR of 0.38 with oTNFi and 0.34 with etanercept. The HR of oTNFi versus etanercept was 1.07 (95% CI 0.74 to 1.54) for any neuroinflammatory event, 0.79 (95% CI 0.51 to 1.22) for DML, 2.20 (95% CI 1.05 to 4.63) for IPN and 0.73 (95% CI 0.34 to 1.56) for MS. In SpA, we observed 179 events (78% DML) with cIR of 0.68 with oTNFi and 0.65 with etanercept. The HR for any neuroinflammatory event, DML, IPN and MS was 1.06 (95% CI 0.75 to 1.50), 1.01 (95% CI 0.68 to 1.50), 1.28 (95% CI 0.61 to 2.69) and 0.94 (95% CI0.53 to 1.69), respectively.ConclusionThe cIRs of neuroinflammatory events are higher in SpA than in RA, but the choice of specific TNFi does not seem to play an important role in the risk of neuroinflammatory events.
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| 52. |
- Diurlin, S., et al.
(författare)
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Gestational diabetes diagnosis in the Swedish Pregnancy Register
- 2023
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 66:Suppl. 1, s. S264-S265
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and aims: The Changing Diagnostic Criteria for Gestational Diabetes (GDM) study (CDC4G) is a stepped wedged randomized controlled trial in Sweden on the effects of introducing the 2013 WHO criteriaf or diagnosing GDM. Almost all Swedish pregnancies are registered in the Swedish Pregnancy Register (SPR). The CDC4G study provides a unique opportunity to validate the GDM diagnosis in the SPR. We aim to 1) validate the diagnosis of GDM in the SPR using the laboratory values from the oral glucose tolerance tests (OGTT) in the CDC4G study as the gold standard; 2) explore effects of change in diagnostic criteria on validity and prevalence of the diagnosis of GDM. Secondary aim is to investigate whether incident GDM diagnoses during pregnancy are recorded by the midwife when entering the follow-up postpartum registration in the SPR.Materials and methods: Data from the SPR were compared with data from the CDC4G eCRF (gold standard measurements: venous OGTT values fasting, 1-h and 2-h) among 6080 screened individuals in 2018. We also investigated if the GDM diagnosis, set at the maternity ward was registered by the midwives at the postpartum follow-up (SPR tickbox). We present the sensitivity, specificity, positive (PPV) and negative (NPV) predictive value for each question. The study was approved by the Uppsala-Örebro regional Ethical Review board (2016/487), and by the Swedish Ethical Review Authority (2019/02148, 2020/02856, 2021/02055).Results: Validating the ICD-code GDM (O24.4) in the Swedish Pregnancy Register resulted in 84.7% sensitivity, 96.7% specificity, PPV of 91.8%, and NPV of 93.5%. The prevalence of the GDM diagnosis more than tripled using the new criteria (Table 1). Both the sensitivity and specificity of the follow-up postpartum registration of GDM were considerably lower than for the GDM ICD-code, 76.6% and 87.6%, respectively. There were some minor differences in the accuracy of the registration before and after the switch to the new criteria for GDM, see table 1.Conclusion: The coding of GDM in clinical practice, that is transferred to the SPR needs to be improved. We recommend researchers to use data based on ICD coding, instead of manually entered SPR data, until the quality of the variable has improved.
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| 53. |
- Ericsson, J., et al.
(författare)
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The lamprey provides a vertebrate blueprint of the mammalian basal ganglia
- 2010
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Konferensbidrag (refereegranskat)abstract
- The basal ganglia are a group of subcortical nuclei that play a prominent role in motor function in mammals as well as in lamprey. The aim of the present study was to characterize the different components of the lamprey basal ganglia, and determine to what extent they correspond to those found in the mammalian basal ganglia. Anatomical tract tracing, immunohistochemistry and acute brain slice patch clamp recordings were employed to address this question.Two pallidal regions were identified in the lamprey; one region, considered homologous to the mammalian globus pallidus, was located ventral to the ementia thalami on the telencephalic/diencephalic border. It receives striatal input from inwardly rectifying neurons (IRNs) and contains GABAergic projection neurons, of which those projecting to the tectum were shown to be tonically active. It also contains neurons immunoreactive for parvalbumin. Separate subpopulations of pallidal neurons project to the optic tectum, the diencephalic and mesencephalic locomotor regions (MLR).Another region, in the midbrain, considered homologous to the substantia nigra pars reticulata receives input from a different subset of IRNs and sends GABAergic projections to the tectum and the diencephalic locomotor region. This midbrain region also contains parvalbumin immunoreactive neurons. The main population of striatal neurons, IRNs, displays the anatomical and electrophysiological hallmarks of mammalian medium spiny neurons, including inward rectification and ramping responses to first spike. It also contains neurons with properties similar to fast-spiking neurons. The striatum receives pallial and thalamic input as well as ascending dopaminergic, serotonergic and histaminergic inputs, similar to that in mammals.Our results suggest that the basic features of the basal ganglia with regard to both structure and function are conserved throughout the vertebrate phylogeny, including striatal/pallidal subdivisions.
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| 54. |
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| 55. |
- Fecchio, Alan, et al.
(författare)
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Global drivers of avian haemosporidian infections vary across zoogeographical regions
- 2021
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Ingår i: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 30:12, s. 2393-2406
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Macroecological analyses provide valuable insights into factors that influence how parasites are distributed across space and among hosts. Amid large uncertainties that arise when generalizing from local and regional findings, hierarchical approaches applied to global datasets are required to determine whether drivers of parasite infection patterns vary across scales. We assessed global patterns of haemosporidian infections across a broad diversity of avian host clades and zoogeographical realms to depict hotspots of prevalence and to identify possible underlying drivers. Location: Global. Time period: 1994–2019. Major taxa studied: Avian haemosporidian parasites (genera Plasmodium, Haemoproteus, Leucocytozoon and Parahaemoproteus). Methods: We amalgamated infection data from 53,669 individual birds representing 2,445 species world-wide. Spatio-phylogenetic hierarchical Bayesian models were built to disentangle potential landscape, climatic and biotic drivers of infection probability while accounting for spatial context and avian host phylogenetic relationships. Results: Idiosyncratic responses of the three most common haemosporidian genera to climate, habitat, host relatedness and host ecological traits indicated marked variation in host infection rates from local to global scales. Notably, host ecological drivers, such as migration distance for Plasmodium and Parahaemoproteus, exhibited predominantly varying or even opposite effects on infection rates across regions, whereas climatic effects on infection rates were more consistent across realms. Moreover, infections in some low-prevalence realms were disproportionately concentrated in a few local hotspots, suggesting that regional-scale variation in habitat and microclimate might influence transmission, in addition to global drivers. Main conclusions: Our hierarchical global analysis supports regional-scale findings showing the synergistic effects of landscape, climate and host ecological traits on parasite transmission for a cosmopolitan and diverse group of avian parasites. Our results underscore the need to account for such interactions, in addition to possible variation in drivers across regions, to produce the robust inference required to predict changes in infection risk under future scenarios.
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| 56. |
- Ferraguti, Martina, et al.
(författare)
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Environmental, geographical and time-related impacts on avian malaria infections in native and introduced populations of house sparrows (Passer domesticus), a globally invasive species
- 2023
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Ingår i: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 32:5, s. 809-823
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The increasing spread of vector-borne diseases has resulted in severe health concerns for humans, domestic animals and wildlife, with changes in land use and the introduction of invasive species being among the main possible causes for this increase. We explored several ecological drivers potentially affecting the local prevalence and richness of avian malaria parasite lineages in native and introduced house sparrows (Passer domesticus) populations. Location: Global. Time period: 2002–2019. Major taxa studied: Avian Plasmodium parasites in house sparrows. Methods: We analysed data from 2,220 samples from 69 localities across all continents, except Antarctica. The influence of environment (urbanization index and human density), geography (altitude, latitude, hemisphere) and time (bird breeding season and years since introduction) were analysed using generalized additive mixed models (GAMMs) and random forests. Results: Overall, 670 sparrows (30.2%) were infected with 22 Plasmodium lineages. In native populations, parasite prevalence was positively related to urbanization index, with the highest prevalence values in areas with intermediate urbanization levels. Likewise, in introduced populations, prevalence was positively associated with urbanization index; however, higher infection occurred in areas with either extreme high or low levels of urbanization. In introduced populations, the number of parasite lineages increased with altitude and with the years elapsed since the establishment of sparrows in a new locality. Here, after a decline in the number of parasite lineages in the first 30 years, an increase from 40 years onwards was detected. Main conclusions: Urbanization was related to parasite prevalence in both native and introduced bird populations. In invaded areas, altitude and time since bird introduction were related to the number of Plasmodium lineages found to be infecting sparrows.
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| 57. |
- Gabrielson, Marike, et al.
(författare)
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Baseline breast tissue characteristics determine the effect of tamoxifen on mammographic density change
- 2024
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Ingår i: International Journal of Cancer. - 0020-7136 .- 1097-0215.
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Tidskriftsartikel (refereegranskat)abstract
- Tamoxifen prevents recurrence of breast cancer and is also approved for preventive, risk-reducing, therapy. Tamoxifen alters the breast tissue composition and decreases the mammographic density. We aimed to test if baseline breast tissue composition influences tamoxifen-associated density change. This biopsy-based study included 83 participants randomised to 6 months daily intake of placebo, 20, 10, 5, 2.5, or 1 mg tamoxifen. The study is nested within the double-blinded tamoxifen dose-determination trial Karolinska Mammography Project for Risk Prediction of Breast Cancer Intervention (KARISMA) Study. Ultrasound-guided core-needle breast biopsies were collected at baseline before starting treatment. Biopsies were quantified for epithelial, stromal, and adipose distributions, and epithelial and stromal expression of proliferation marker Ki67, oestrogen receptor (ER) and progesterone receptor (PR). Mammographic density was measured using STRATUS. We found that greater mammographic density at baseline was positively associated with stromal area and inversely associated with adipose area and stromal expression of ER. Premenopausal women had greater mammographic density and epithelial tissue, and expressed more epithelial Ki67, PR, and stromal PR, compared to postmenopausal women. In women treated with tamoxifen (1–20 mg), greater density decrease was associated with higher baseline density, epithelial Ki67, and stromal PR. Women who responded to tamoxifen with a density decrease had on average 17% higher baseline density and a 2.2-fold higher PR expression compared to non-responders. Our results indicate that features in the normal breast tissue before tamoxifen exposure influences the tamoxifen-associated density decrease, and that the age-associated difference in density change may be related to age-dependant differences in expression of Ki67 and PR.
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| 58. |
- Gabrielson, Marike, et al.
(författare)
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Effects of tamoxifen on normal breast tissue histological composition : Results from a randomised six-arm placebo-controlled trial in healthy women
- 2023
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 152:11, s. 2362-2372
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Tidskriftsartikel (refereegranskat)abstract
- Tamoxifen prevents recurrence of breast cancer and is suggested for preventive risk-reducing therapy. Tamoxifen reduces mammographic density, a proxy for therapy response, but little is known about its effects in remodelling normal breast tissue. Our study, a substudy within the double-blinded dose-determination trial KARISMA, investigated tamoxifen-specific changes in breast tissue composition and histological markers in healthy women. We included 83 healthy women randomised to 6 months daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. The groups were combined to “no dose” (0-1 mg), “low-dose” (2.5-5 mg) or “high-dose” (10-20 mg) of tamoxifen. Ultrasound-guided biopsies were collected before and after tamoxifen exposure. In each biopsy, epithelial, stromal and adipose tissues was quantified, and expression of epithelial and stromal Ki67, oestrogen receptor (ER) and progesterone receptor (PR) analysed. Mammographic density using STRATUS was measured at baseline and end-of-tamoxifen-exposure. We found that different doses of tamoxifen reduced mammographic density and glandular-epithelial area in premenopausal women and associated with reduced epithelium and increased adipose tissue. High-dose tamoxifen also decreased epithelial ER and PR expressions in premenopausal women. Premenopausal women with the greatest reduction in proliferation also had the greatest epithelial reduction. In postmenopausal women, high-dose tamoxifen decreased the epithelial area with no measurable density decrease. Tamoxifen at both low and high doses influences breast tissue composition and expression of histological markers in the normal breast. Our findings connect epithelial proliferation with tissue remodelling in premenopausal women and provide novel insights to understanding biological mechanisms of primary prevention with tamoxifen.
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| 59. |
- Ghandriz, Toheed, 1982, et al.
(författare)
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Impact of automated driving systems on road freight transport and electrified propulsion of heavy vehicles
- 2020
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Ingår i: Transportation Research, Part C: Emerging Technologies. - : Elsevier BV. - 0968-090X. ; 115
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Tidskriftsartikel (refereegranskat)abstract
- The technological barriers to automated driving systems (ADS) are being quickly overcome to deploy on–road vehicles that do not require a human driver on–board. ADS have opened up possibilities to improve mobility, productivity, logistics planning, and energy consumption. However, further enhancements in productivity and energy consumption are required to reach CO2–reduction goals, owing to increased demands on transportation. In particular, in the freight sector, incorporation of automation with electrification can meet necessities of sustainable transport. However, the profitability of battery electric heavy vehicles (BEHVs) remains a concern. This study found that ADS led to profitability of BEHVs, which remained profitable for increased travel ranges by a factor of four compared to that of BEHVs driven by humans. Up to 20% reduction in the total cost of ownership of BEHVs equipped with ADS could be achieved by optimizing the electric propulsion system along with the infrastructure for a given transportation task. In that case, the optimized propulsion system might not be similar to that of a BEHV with a human driver. To obtain the results, the total cost of ownership was minimized numerically for 3072 different transportation scenarios that showed the effects of travel distance, road hilliness, average reference speed, and vehicle size on the incorporated electrification and automation, and compared to that of conventional combustion–powered heavy vehicles.
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| 60. |
- Ghandriz, Toheed, 1982, et al.
(författare)
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Optimization Based Design of Heterogeneous Truck Fleet and Electric Propulsion
- 2016
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Ingår i: Proceedings, ITSC. IEEE 19th International Conference on Intelligent Transportation Systems (ITSC), November 1-4, 2016, Rio de Janeiro, Brazil. - 9781509018895 ; , s. Art no 7795575, Pages 328-335
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Konferensbidrag (refereegranskat)abstract
- Many researches have been focused on vehicle routing problem during past decades where subject vehicles are previously fully designed and ready to start operation. Further, extensive studies have been done on powertrain design irrespective of the routes where the vehicle is going to be employed. In the present paper, we try to define a new branch of problems where the vehicle design, in particular its propulsion system and loading capacity, is treated simultaneously with the routing problem. The focus is on optimization based design of heterogeneous electric truck fleet to perform a prescribed task with a lowest cost on an available set of routes. The approach is illustrated in a simple case study problem. It is shown that long heavy combination vehicles are energy-efficient but not cost-optimal on short routes.
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