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- Patel, Y., et al.
(författare)
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Virtual Ontogeny of Cortical Growth Preceding Mental Illness
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 92:4, s. 299 - 313
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Tidskriftsartikel (refereegranskat)abstract
- Background: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. Methods: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. Results: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. Conclusions: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.
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| 3. |
- Baumgartner, D., et al.
(författare)
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INFLUENCE OF HEAD ROTATIONAL ACCELERATION PULSE SHAPE ON BRAIN TISSUE STRAINS
- 2014
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Ingår i: Journal of Neurotrauma. - 0897-7151. ; 31:12, s. A121-A121
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Brain tolerance to rotational acceleration is relevant for understanding injury thresholds and development of injury mitigation techniques for automobiles and sporting events. This computational-modeling study outlined effects of head rotational acceleration pulse shape on strains within brain tissues. A detailed finite element model of the human skull and brain was developed and validated previously. The model was exercised using realistic rotational accelerations with different magnitude and duration characteristics, and the principal strain re- sponse was extracted for parietal cortex, hippocampus, thalamus, and hypothalamus. Rotational acceleration magnitude was varied to three levels: 3.6krad/s 2 (M1), 5.3krad/s 2 (M2), and 6.6krad/s 2 (M3). Duration was varied to 9msec (D1), 18msec (D2), and 27msec (D3). Hippocampus and hypothalamus sustained more strain than cortex and thalamus. With increasing acceleration magnitude from M1 to M2 and M2 to M3, strain in all brain regions was uniformly increased by 42% and 80%. However, strains demonstrated regionally dependent chan- ges with increasing duration (D1 to D3): 68%, 37%, 33% and 14% in parietal cortex, hippocampus, thalamus and hypothalamus, respec- tively. The trend was consistent for all acceleration magnitudes. This study demonstrated differing and independent effects of rotational acceleration magnitude and duration on strains within brain tissues during rotational acceleration. Magnitude has long been a correlate of injury severity and this study supports that finding in that increased acceleration magnitudes led to uniformly higher brain tissue strains (higher injury risk). However, rotational acceleration duration chan- ged the strain distribution within the brain, resulting in different injury risks in different brain regions. This finding is significant as changing strain distribution with different durations can manifest as different injury distributions within the brain and different neuropsychological outcomes following exposure to head rotational acceleration.
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| 4. |
- Hoenigl, M., et al.
(författare)
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Guideline adherence and survival of patients with candidaemia in Europe: results from the ECMM Candida III multinational European observational cohort study
- 2023
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Ingår i: Lancet. Infectious Diseases. - : Elsevier BV. - 1473-3099 .- 1474-4457. ; 23:6, s. 751-761
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Tidskriftsartikel (refereegranskat)abstract
- Background The European Confederation of Medical Mycology (ECMM) collected data on epidemiology, risk factors, treatment, and outcomes of patients with culture-proven candidaemia across Europe to assess how adherence to guideline recommendations is associated with outcomes.Methods In this observational cohort study, 64 participating hospitals located in 20 European countries, with the number of eligible hospitals per country determined by population size, included the first ten consecutive adults with culture-proven candidaemia after July 1, 2018, and entered data into the ECMM Candida Registry (FungiScope CandiReg). We assessed ECMM Quality of Clinical Candidaemia Management (EQUAL Candida) scores reflecting adherence to recommendations of the European Society of Clinical Microbiology and Infectious Diseases and the Infectious Diseases Society of America guidelines.Findings 632 patients with candidaemia were included from 64 institutions. Overall 90-day mortality was 43% (265/617), and increasing age, intensive care unit admission, point increases in the Charlson comorbidity index score, and Candida tropicalis as causative pathogen were independent baseline predictors of mortality in Cox regression analysis. EQUAL Candida score remained an independent predictor of mortality in the multivariable Cox regression analyses after adjusting for the baseline predictors, even after restricting the analysis to patients who survived for more than 7 days after diagnosis (adjusted hazard ratio 1 & BULL;08 [95% CI 1 & BULL;04-1 & BULL;11; p<0 & BULL;0001] in patients with a central venous catheter and 1 & BULL;09 [1 & BULL;05-1 & BULL;13; p<0 & BULL;0001] in those without one, per one score point decrease). Median duration of hospital stay was 15 days (IQR 4-30) after diagnosis of candidaemia and was extended specifically for completion of parenteral therapy in 100 (16%) of 621 patients. Initial echinocandin treatment was associated with lower overall mortality and longer duration of hospital stay among survivors than treatment with other antifungals.Interpretation Although overall mortality in patients with candidaemia was high, our study indicates that adherence to clinical guideline recommendations, reflected by higher EQUAL Candida scores, might increase survival. New antifungals, with similar activity as current echinocandins but with longer half-lives or oral bioavailability, are needed to reduce duration of hospital stay.
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| 5. |
- Ji, S., et al.
(författare)
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Use of Brain Biomechanical Models for Monitoring Impact Exposure in Contact Sports
- 2022
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Ingår i: Annals of Biomedical Engineering. - : Springer Nature. - 0090-6964 .- 1573-9686. ; 50:11, s. 1389-1408
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Tidskriftsartikel (refereegranskat)abstract
- Head acceleration measurement sensors are now widely deployed in the field to monitor head kinematic exposure in contact sports. The wealth of impact kinematics data provides valuable, yet challenging, opportunities to study the biomechanical basis of mild traumatic brain injury (mTBI) and subconcussive kinematic exposure. Head impact kinematics are translated into brain mechanical responses through physics-based computational simulations using validated brain models to study the mechanisms of injury. First, this article reviews representative legacy and contemporary brain biomechanical models primarily used for blunt impact simulation. Then, it summarizes perspectives regarding the development and validation of these models, and discusses how simulation results can be interpreted to facilitate injury risk assessment and head acceleration exposure monitoring in the context of contact sports. Recommendations and consensus statements are presented on the use of validated brain models in conjunction with kinematic sensor data to understand the biomechanics of mTBI and subconcussion. Mainly, there is general consensus that validated brain models have strong potential to improve injury prediction and interpretation of subconcussive kinematic exposure over global head kinematics alone. Nevertheless, a major roadblock to this capability is the lack of sufficient data encompassing different sports, sex, age and other factors. The authors recommend further integration of sensor data and simulations with modern data science techniques to generate large datasets of exposures and predicted brain responses along with associated clinical findings. These efforts are anticipated to help better understand the biomechanical basis of mTBI and improve the effectiveness in monitoring kinematic exposure in contact sports for risk and injury mitigation purposes.
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| 7. |
- Alisjahbana, A, et al.
(författare)
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CD5 Surface Expression Marks Intravascular Human Innate Lymphoid Cells That Have a Distinct Ontogeny and Migrate to the Lung
- 2021
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 12, s. 752104-
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Tidskriftsartikel (refereegranskat)abstract
- Innate lymphoid cells (ILCs) contribute to immune defense, yet it is poorly understood how ILCs develop and are strategically positioned in the lung. This applies especially to human ILCs due to the difficulty of studying them in vivo. Here we investigated the ontogeny and migration of human ILCs in vivo with a humanized mouse model (“MISTRG”) expressing human cytokines. In addition to known tissue-resident ILC subsets, we discovered CD5-expressing ILCs that predominantly resided within the lung vasculature and in the circulation. CD5+ ILCs contained IFNγ-producing mature ILC1s as well as immature ILCs that produced ILC effector cytokines under polarizing conditions in vitro. CD5+ ILCs had a distinct ontogeny compared to conventional CD5- ILCs because they first appeared in the thymus, spleen and liver rather than in the bone marrow after transplantation of MISTRG mice with human CD34+ hematopoietic stem and progenitor cells. Due to their strategic location, human CD5+ ILCs could serve as blood-borne sentinels, ready to be recruited into the lung to respond to environmental challenges. This work emphasizes the uniqueness of human CD5+ ILCs in terms of their anatomical localization and developmental origin compared to well-studied CD5- ILCs.
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