| 1. |
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Overview of the JET results
- 2015
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In: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 55:10
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Journal article (peer-reviewed)
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| 7. |
- Olalde, I., et al.
(author)
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The Beaker phenomenon and the genomic transformation of northwest Europe
- 2018
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 555:7695, s. 190-196
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Journal article (peer-reviewed)abstract
- From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain's gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries.
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| 10. |
- Maier, O., et al.
(author)
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ISLES 2015-A public evaluation benchmark for ischemic stroke lesion segmentation from multispectral MRI
- 2017
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In: Medical Image Analysis. - : Elsevier BV. - 1361-8415 .- 1361-8423. ; 35, s. 250-269
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Journal article (peer-reviewed)abstract
- Ischemic stroke is the most common cerebrovascular disease, and its diagnosis, treatment, and study relies on non-invasive imaging. Algorithms for stroke lesion segmentation from magnetic resonance imaging (MRI) volumes are intensely researched, but the reported results are largely incomparable due to different datasets and evaluation schemes. We approached this urgent problem of comparability with the Ischemic Stroke Lesion Segmentation (ISLES) challenge organized in conjunction with the MICCAI 2015 conference. In this paper we propose a common evaluation framework, describe the publicly available datasets, and present the results of the two sub-challenges: Sub-Acute Stroke Lesion Segmentation (SISS) and Stroke Perfusion Estimation (SPES). A total of 16 research groups participated with a wide range of state-of-the-art automatic segmentation algorithms. A thorough analysis of the obtained data enables a critical evaluation of the current state-of-the-art, recommendations for further developments, and the identification of remaining challenges. The segmentation of acute perfusion lesions addressed in SPES was found to be feasible. However, algorithms applied to sub-acute lesion segmentation in SISS still lack accuracy. Overall, no algorithmic characteristic of any method was found to perform superior to the others. Instead, the characteristics of stroke lesion appearances, their evolution, and the observed challenges should be studied in detail. The annotated ISLES image datasets continue to be publicly available through an online evaluation system to serve as an ongoing benchmarking resource (www.isles-challenge.org).
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| 11. |
- Thompson, Robin N., et al.
(author)
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Key questions for modelling COVID-19 exit strategies
- 2020
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In: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 287:1932
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Journal article (peer-reviewed)abstract
- Combinations of intense non-pharmaceutical interventions (lockdowns) were introduced worldwide to reduce SARS-CoV-2 transmission. Many governments have begun to implement exit strategies that relax restrictions while attempting to control the risk of a surge in cases. Mathematical modelling has played a central role in guiding interventions, but the challenge of designing optimal exit strategies in the face of ongoing transmission is unprecedented. Here, we report discussions from the Isaac Newton Institute 'Models for an exit strategy' workshop (11-15 May 2020). A diverse community of modellers who are providing evidence to governments worldwide were asked to identify the main questions that, if answered, would allow for more accurate predictions of the effects of different exit strategies. Based on these questions, we propose a roadmap to facilitate the development of reliable models to guide exit strategies. This roadmap requires a global collaborative effort from the scientific community and policymakers, and has three parts: (i) improve estimation of key epidemiological parameters; (ii) understand sources of heterogeneity in populations; and (iii) focus on requirements for data collection, particularly in low-to-middle-income countries. This will provide important information for planning exit strategies that balance socio-economic benefits with public health.
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| 12. |
- Patterson, Nick, et al.
(author)
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Large-scale migration into Britain during the Middle to Late Bronze Age
- 2022
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In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; , s. 588-594
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Journal article (peer-reviewed)abstract
- Present-day people from England and Wales harbour more ancestry derived from Early European Farmers (EEF) than people of the Early Bronze Age1. To understand this, we generated genome-wide data from 793 individuals, increasing data from the Middle to Late Bronze and Iron Age in Britain by 12-fold, and Western and Central Europe by 3.5-fold. Between 1000 and 875 BC, EEF ancestry increased in southern Britain (England and Wales) but not northern Britain (Scotland) due to incorporation of migrants who arrived at this time and over previous centuries, and who were genetically most similar to ancient individuals from France. These migrants contributed about half the ancestry of Iron Age people of England and Wales, thereby creating a plausible vector for the spread of early Celtic languages into Britain. These patterns are part of a broader trend of EEF ancestry becoming more similar across central and western Europe in the Middle to Late Bronze Age, coincident with archaeological evidence of intensified cultural exchange2-6. There was comparatively less gene flow from continental Europe during the Iron Age, and Britain's independent genetic trajectory is also reflected in the rise of the allele conferring lactase persistence to ~50% by this time compared to ~7% in central Europe where it rose rapidly in frequency only a millennium later. This suggests that dairy products were used in qualitatively different ways in Britain and in central Europe over this period.
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| 13. |
- Vega, Paige N., et al.
(author)
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Cancer-Associated Fibroblasts and Squamous Epithelial Cells Constitute a Unique Microenvironment in a Mouse Model of Inflammation-Induced Colon Cancer
- 2022
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In: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 12
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Journal article (peer-reviewed)abstract
- The tumor microenvironment plays a key role in the pathogenesis of colorectal tumors and contains various cell types including epithelial, immune, and mesenchymal cells. Characterization of the interactions between these cell types is necessary for revealing the complex nature of tumors. In this study, we used single-cell RNA-seq (scRNA-seq) to compare the tumor microenvironments between a mouse model of sporadic colorectal adenoma (Lrig1(CreERT2/+);Apc(2lox14/+)) and a mouse model of inflammation-driven colorectal cancer induced by azoxymethane and dextran sodium sulfate (AOM/DSS). While both models develop tumors in the distal colon, we found that the two tumor types have distinct microenvironments. AOM/DSS tumors have an increased abundance of two populations of cancer-associated fibroblasts (CAFs) compared with APC tumors, and we revealed their divergent spatial association with tumor cells using multiplex immunofluorescence (MxIF) imaging. We also identified a unique squamous cell population in AOM/DSS tumors, whose origins were distinct from anal squamous epithelial cells. These cells were in higher proportions upon administration of a chemotherapy regimen of 5-Fluorouracil/Irinotecan. We used computational inference algorithms to predict cell-cell communication mediated by ligand-receptor interactions and downstream pathway activation, and identified potential mechanistic connections between CAFs and tumor cells, as well as CAFs and squamous epithelial cells. This study provides important preclinical insight into the microenvironment of two distinct models of colorectal tumors and reveals unique roles for CAFs and squamous epithelial cells in the AOM/DSS model of inflammation-driven cancer.
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| 15. |
- Bodin, Fernando, 1991, et al.
(author)
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The Association of Cigarette Smoking With High-Frequency Heart Rate Variability: An Ecological Momentary Assessment Study
- 2017
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In: Psychosomatic Medicine. - : Ovid Technologies (Wolters Kluwer Health). - 0033-3174 .- 1534-7796. ; 79:9, s. 1045-1050
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Journal article (peer-reviewed)abstract
- Objective Evidence from both laboratory and observational studies suggests that acute and chronic smoking leads to reduced high-frequency heart rate variability (HF-HRV), a measure of cardiac vagal regulation. We used ecological momentary assessment (EMA) to study the effect of smoking on concurrent HF-HRV in a trial measuring the effects of hostility reduction and compared 24-hour HF-HRV in smokers and nonsmokers. Method Ambulatory electrocardiogram data were collected before randomization from 149 healthy individuals with high hostility levels (20-45 years, body mass index 32 kg/m(2)) and paired with concurrent EMA ratings of smoking and physical position during waking hours. A multilevel mixed model was estimated associating ln(HF-HRV) from smoking status (between-person factor) and person-centered momentary smoking (within-person factor, treated as a random effect), adjusting for momentary physical position, medication use, and consumption of alcohol and caffeine. Results Thirty-five smokers and 114 nonsmokers provided both EMA and HF-HRV data. Within smokers, ln HF-HRV was reduced by 0.31 millisecond(2) (p = .04) when participants reported having recently smoked cigarettes, compared with when they had not. The 24-hour HF-HRV was significantly lower in smokers (M [SD] = 5.24 [0.14] milliseconds(2)) than nonsmokers (5.63 0.07 milliseconds(2), p = .01). Conclusions In healthy smokers with high hostility levels used as their own controls during daily living, smoking acutely reduced HF-HRV. HF-HRV was also reduced in smokers as compared with nonsmokers. Although limited by a small sample of individuals with high hostility levels, these findings nonetheless provide additional evidence that cardiac vagal regulation is lowered by cigarette smoking, which may be one of the numerous pathophysiological effects of smoking.
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| 16. |
- Choi, Hyungryul J., et al.
(author)
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Superoleophilic Titania Nanoparticle Coatings with Fast Fingerprint Decomposition and High Transparency
- 2017
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In: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 9:9, s. 8354-8360
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Journal article (peer-reviewed)abstract
- Low surface tension sebaceous liquids such as human fingerprint oils are readily deposited on high energy surfaces such as clean glass, leaving smudges that significantly lower transparency. There have been several attempts to prevent formation of these dactylograms on glass by employing oil-repellent textured surfaces. However, nanotextured superoleophobic coatings typically scatter visible light, and the intrinsic thermodynamic metastability of the composite superoleophobic state can result in failure of the oil repellency under moderate contact pressure. We develop titania-based porous nanoparticle coatings that are superoleophilic and highly transparent and which exhibit short time scales for decomposition of fingerprint oils under ultraviolet light. The mechanism by which a typical dactylogram is consumed combines wicking of the sebum into the nanoporous titania structure followed by photocatalytic degradation. We envision a wide range of applications because these TiO2 nanostructured surfaces remain photocatalytically active against fingerprint oils in natural sunlight and are also compatible with flexible glass substrates.
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| 17. |
- Frithiof, Robert, et al.
(author)
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Intracarotid hypertonic sodium chloride differentially modulates sympathetic nerve activity to the heart and kidney
- 2014
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In: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 306:8, s. R567-R575
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Journal article (peer-reviewed)abstract
- Frithiof R, Xing T, McKinley MJ, May CN, Ramchandra R. Intracarotid hypertonic sodium chloride differentially modulates sympathetic nerve activity to the heart and kidney. Am J Physiol Regul Integr Comp Physiol 306: R567-R575, 2014. First published February 12, 2014; doi: 10.1152/ajpregu. 00460.2013.-Hypertonic NaCl infused into the carotid arteries increases mean arterial pressure (MAP) and changes sympathetic nerve activity (SNA) via cerebral mechanisms. We hypothesized that elevated sodium levels in the blood supply to the brain would induce differential responses in renal and cardiac SNA via sensors located outside the blood-brain barrier. To investigate this hypothesis, we measured renal and cardiac SNA simultaneously in conscious sheep during intracarotid infusions of NaCl (1.2 M), sorbitol (2.4 M), or urea (2.4 M) at 1 ml/min for 4 min into each carotid. Intracarotid NaCl significantly increased MAP (91 +/- 2 to 97 +/- 3 mmHg, P < 0.05) without changing heart rate (HR). Intracarotid NaCl was associated with no change in cardiac SNA (11 +/- 5.0%), but a significant inhibition of renal SNA (-32.5 +/- 6.4%, P < 0.05). Neither intracarotid sorbitol nor urea changed MAP, HR, central venous pressure, cardiac SNA, and renal SNA. The changes in MAP and renal SNA were completely abolished by microinjection of the GABA agonist muscimol (5 mM, 500 nl each side) into the paraventricular nucleus of the hypothalamus (PVN). Infusion of intracarotid NaCl for 20 min stimulated a larger increase in water intake (1,100 +/- 75 ml) than intracarotid sorbitol (683 +/- 125 ml) or intracarotid urea (0 ml). These results demonstrate that acute increases in blood sodium levels cause a decrease in renal SNA, but no change in cardiac SNA in conscious sheep. These effects are mediated by cerebral sensors located outside the blood-brain barrier that are more responsive to changes in sodium concentration than osmolality. The renal sympathoinhibitory effects of sodium are mediated via a pathway that synapses in the PVN.
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| 18. |
- Hajjari, Parisa, et al.
(author)
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The Effect of Hostility Reduction on Autonomic Control of the Heart and Vasculature: A Randomized Controlled Trial
- 2016
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In: Psychosomatic Medicine. - : Ovid Technologies (Wolters Kluwer Health). - 0033-3174. ; 78:4, s. 481-491
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Journal article (peer-reviewed)abstract
- Objective Hostility is associated with coronary artery disease. One candidate mechanism may be autonomic nervous system (ANS) dysregulation. In this study, we report the effect of cognitive behavioral treatment on ANS regulation. Methods Participants were 158 healthy young adults, high in hostility measured by the Cook-Medley Hostility and Spielberger Trait Anger scales. Participants were also interviewed using the Interpersonal Hostility Assessment Technique. They were randomized to a 12-week cognitive behavioral treatment program for reducing hostility or a wait-list control group. The outcome measures were preejection period, low-frequency blood pressure variability, and high-frequency heart rate variability measured at rest and in response to and recovery from cognitive and orthostatic challenge. Linear-mixed models were used to examine group by session and group by session by period interactions while controlling for sex and age. Contrasts of differential group and session effects were used to examine reactivity and recovery from challenge. Results After Bonferroni correction, two-way and three-way interactions failed to achieve significance for preejection period, low-frequency blood pressure variability, or high-frequency heart rate variability (p > .002), indicating that hostility reduction treatment failed to influence ANS indices. Conclusions Reduction in anger and hostility failed to alter ANS activity at rest or in response to or recovery from challenge. These findings raise questions about whether autonomic dysregulation represents a pathophysiological link between hostility and heart disease.
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| 19. |
- Lindgren, Martin, et al.
(author)
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Effects of aerobic conditioning on cardiovascular sympathetic response to and recovery from challenge
- 2013
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In: Psychophysiology. - : Wiley. - 1540-5958 .- 0048-5772. ; 50:10, s. 963-973
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Journal article (peer-reviewed)abstract
- Exercise has widely documented cardioprotective effects, but the mechanisms behind these effects are still poorly understood. Here, we test the hypothesis that aerobic training lowers cardiovascular sympathetic responses to and speeds recovery from challenge. We conducted a randomized, controlled trial contrasting aerobic versus strength training on indices of cardiac (pre-ejection period, PEP) and vascular (low-frequency blood pressure variability, LF-BPV) sympathetic responses to and recovery from psychological and orthostatic challenge in 149 young, healthy, sedentary adults. Aerobic and strength training did not alter PEP or LF-BPV reactivity to or recovery from challenge. These findings, from a large randomized, controlled trial using an intent-to-treat design, show that moderate aerobic exercise training has no effect on PEP and LF-BPV reactivity to or recovery from psychological or orthostatic challenge. In healthy young adults, the cardioprotective effects of exercise training are unlikely to be mediated by changes in sympathetic activity. Copyright © 2013 Society for Psychophysiological Research.
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| 20. |
- Marin, Robin
(author)
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Computational Modeling, Parameterization, and Evaluation of the Spread of Diseases
- 2022
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Doctoral thesis (other academic/artistic)abstract
- Computer simulations play a vital role in the modeling of infectious diseases. Different modeling regimes fit specific purposes, from ordinary differential equations to probabilistic formulations. Throughout the COVID-19 pandemic, we have seen how the results from these computational models can come to dictate our daily lives and the importance of reliable results. This thesis aims to address the challenge of exploiting the increase in available computational power to build accurate models with well-understood uncertainties. The latter is essential when basing decisions on any model predictions.Data collection relevant to epidemiology is expanding, and methods to incorporate models in data fitting need to follow suit. This thesis applies the Bayesian framework connecting data with models in a probabilistic setting. We propose simulation-based inference methods that allow for the use of complex models otherwise excluded due to their intractable likelihoods. Our computational set-up exemplifies how modelers can deploy Bayesian inference in large-scale, real-world data environments.The thesis includes four papers relevant for modelers considering dynamic systems, approximate Bayesian inference, or epidemics. Paper I finds the approximate posterior of a complex chemical reaction network and estimates the prior and posterior uncertainties using the pathwise Fisher information matrix, thus framing our methodology in a fully synthetic setting. Paper II constructs a disease spread model for the spread of a verotoxigenic E. coli prevalent in the Swedish cattle population. The data includes a high-resolution transport network and actual bacterial-swab observations from selected farms. The results show that even if the data is sparse in space and time, it is still possible to recover a posterior that replicates the data and is viable for mitigation evaluations. Paper III studies a form of meta-models, the Ornstein-Uhlenbeck process, and how they approximate epidemiological models and enable broad analysis. We state an analytical limit of what is possible to learn from data subject to binary filters with confirming numerical examples. Finally, Paper IV finds a posterior model of the COVID-19 pandemic in Sweden and the 21 regions using a Kalman filter approximation. The findings result in a probabilistic regional surveillance tool for an epidemic at a national scale with considerable cost-cutting potential independent of large-scale testing of individuals.In conclusion, the thesis examines how reasonably realistic and computationally expensive epidemic models can be adapted to data using a Bayesian framework without compromising model complexity and estimating uncertainties that further support decision-making.
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| 21. |
- Mehta, Raghav, et al.
(author)
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QU-BraTS : MICCAI BraTS 2020 Challenge on QuantifyingUncertainty in Brain Tumor Segmentation - Analysis of Ranking Scores and Benchmarking Results
- 2022
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In: Journal of Machine Learning for Biomedical Imaging. - 2766-905X. ; , s. 1-54
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Journal article (peer-reviewed)abstract
- Deep learning (DL) models have provided the state-of-the-art performance in a wide variety of medical imaging benchmarking challenges, including the Brain Tumor Segmentation (BraTS) challenges. However, the task of focal pathology multi-compartment segmentation (e.g., tumor and lesion sub-regions) is particularly challenging, and potential errors hinder the translation of DL models into clinical workflows. Quantifying the reliability of DL model predictions in the form of uncertainties, could enable clinical review of the most uncertain regions, thereby building trust and paving the way towards clinical translation. Recently, a number of uncertainty estimation methods have been introduced for DL medical image segmentation tasks. Developing scores to evaluate and compare the performance of uncertainty measures will assist the end-user in making more informed decisions. In this study, we explore and evaluate a score developed during the BraTS 2019-2020 task on uncertainty quantification (QU-BraTS), and designed to assess and rank uncertainty estimates for brain tumor multi-compartment segmentation. This score (1) rewards uncertainty estimates that produce high confidence in correct assertions, and those that assign low confidence levels at incorrect assertions, and (2) penalizes uncertainty measures that lead to a higher percentages of under-confident correct assertions. We further benchmark the segmentation uncertainties generated by 14 independent participating teams of QU-BraTS 2020, all of which also participated in the main BraTS segmentation task. Overall, our findings confirm the importance and complementary value that uncertainty estimates provide to segmentation algorithms, and hence highlight the need for uncertainty quantification in medical image analyses. Our evaluation code is made publicly available at https://github.com/RagMeh11/QU-BraTS
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| 22. |
- Ramchandra, Rohit, et al.
(author)
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The role of the paraventricular nucleus of the hypothalamus in the regulation of cardiac and renal sympathetic nerve activity in conscious normal and heart failure sheep.
- 2013
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In: Journal of Physiology. - : Wiley. - 0022-3751 .- 1469-7793. ; 591:1, s. 93-107
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Journal article (peer-reviewed)abstract
- The paraventricular nucleus of the hypothalamus (PVN) plays a major role in central cardiovascular and volume control, and has been implicated in controlling sympathetic nerve activity (SNA) during volume expansion and in heart failure (HF). The objectives were to determine the role of the PVN on cardiac and renal SNA (CSNA and RSNA) in conscious normal sheep and sheep with pacing-induced heart failure. In normovolaemic sheep in the normal state and in HF, bilateral microinjection of the GABA agonist muscimol (2 mm, 500 nl), had no effects on resting mean arterial pressure (MAP), heart rate (HR), CSNA or RSNA. In addition, neither chemical inhibition of the PVN using the inhibitory amino acid glycine (0.5 m, 500 nl), nor electrolytic lesion of the PVN reduced the elevated level of CSNA in HF. Dysinhibition of the PVN with bilateral microinjection of bicuculline (1 mm, 500 nl) in normal sheep increased MAP, HR and CSNA, but decreased RSNA, whereas in HF bicuculline had no effects on MAP, HR or CSNA, but inhibited RSNA. During volume expansion in normal sheep, muscimol reversed the inhibition of RSNA, but not of CSNA. In summary, removal of endogenous GABAergic inhibition to the PVN indicated that CSNA is normally under inhibitory control. Although this inhibition was absent in HF, the responses to pharmacological inhibition, or lesion of the PVN, indicates that it does not drive the increased CSNA in HF. These findings indicate the PVN has a greater influence on RSNA than CSNA in the resting state in normal and HF sheep, and during volume expansion in normal sheep.
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