| 1. |
- Ferrando, Carlos, et al.
(författare)
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Effects of oxygen on post-surgical infections during an individualised perioperative open-lung ventilatory strategy : a randomised controlled trial
- 2020
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Ingår i: British Journal of Anaesthesia. - : ELSEVIER SCI LTD. - 0007-0912 .- 1471-6771. ; 124:1, s. 110-120
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to examine whether using a high fraction of inspired oxygen (FIO2) in the context of an individualised intra- and postoperative open-lung ventilation approach could decrease surgical site infection (SSI) in patients scheduled for abdominal surgery. Methods: We performed a multicentre, randomised controlled clinical trial in a network of 21 university hospitals from June 6, 2017 to July 19, 2018. Patients undergoing abdominal surgery were randomly assigned to receive a high (0.80) or conventional (0.3) FIO2 during the intraoperative period and during the first 3 postoperative hours. All patients were mechanically ventilated with an open-lung strategy, which included recruitment manoeuvres and individualised positive end-expiratory pressure for the best respiratory-system compliance, and individualised continuous postoperative airway pressure for adequate peripheral oxyhaemoglobin saturation. The primary outcome was the prevalence of SSI within the first 7 postoperative days. The secondary outcomes were composites of systemic complications, length of intensive care and hospital stay, and 6-month mortality. Results: We enrolled 740 subjects: 371 in the high FIO2 group and 369 in the low FIO2 group. Data from 717 subjects were available for final analysis. The rate of SSI during the first postoperative week did not differ between high (8.9%) and low (9.4%) FIO2 groups (relative risk [RR]: 0.94; 95% confidence interval [CI]: 0.59-1.50; P=0.90]). Secondary outcomes, such as atelectasis (7.7% vs 9.8%; RR: 0.77; 95% CI: 0.48-1.25; P=0.38) and myocardial ischaemia (0.6% [n=2] vs 0% [n=0]; P=0.47) did not differ between groups. Conclusions: An oxygenation strategy using high FIO2 compared with conventional FIO2 did not reduce postoperative SSIs in abdominal surgery. No differences in secondary outcomes or adverse events were found.
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| 2. |
- Insausti, Ricardo, et al.
(författare)
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Ex vivo, in situ perfusion protocol for human brain fixation compatible with microscopy, MRI techniques, and anatomical studies
- 2023
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Ingår i: Frontiers in Neuroanatomy. - : Frontiers Media SA. - 1662-5129. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- We present a method for human brain fixation based on simultaneous perfusion of 4% paraformaldehyde through carotids after a flush with saline. The left carotid cannula is used to perfuse the body with 10% formalin, to allow further use of the body for anatomical research or teaching. The aim of our method is to develop a vascular fixation protocol for the human brain, by adapting protocols that are commonly used in experimental animal studies. We show that a variety of histological procedures can be carried out (cyto- and myeloarchitectonics, histochemistry, immunohistochemistry, intracellular cell injection, and electron microscopy). In addition, ex vivo, ex situ high-resolution MRI (9.4T) can be obtained in the same specimens. This procedure resulted in similar morphological features to those obtained by intravascular perfusion in experimental animals, provided that the postmortem interval was under 10 h for several of the techniques used and under 4 h in the case of intracellular injections and electron microscopy. The use of intravascular fixation of the brain inside the skull provides a fixed whole human brain, perfectly fitted to the skull, with negligible deformation compared to conventional techniques. Given this characteristic of ex vivo, in situ fixation, this procedure can probably be considered the most suitable one available for ex vivo MRI scans of the brain. We describe the compatibility of the method proposed for intravascular fixation of the human brain and fixation of the donor’s body for anatomical purposes. Thus, body donor programs can provide human brain tissue, while the remainder of the body can also be fixed for anatomical studies. Therefore, this method of human brain fixation through the carotid system optimizes the procurement of human brain tissue, allowing a greater understanding of human neurological diseases, while benefiting anatomy departments by making the remainder of the body available for teaching purposes.
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| 3. |
- Ravikumar, Sadhana, et al.
(författare)
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Ex vivo MRI atlas of the human medial temporal lobe : characterizing neurodegeneration due to tau pathology
- 2021
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Ingår i: Acta Neuropathologica Communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Tau neurofibrillary tangle (NFT) pathology in the medial temporal lobe (MTL) is closely linked to neurodegeneration, and is the early pathological change associated with Alzheimer’s disease (AD). To elucidate patterns of structural change in the MTL specifically associated with tau pathology, we compared high-resolution ex vivo MRI scans of human postmortem MTL specimens with histology-based pathological assessments of the MTL. MTL specimens were obtained from twenty-nine brain donors, including patients with AD, other dementias, and individuals with no known history of neurological disease. Ex vivo MRI scans were combined using a customized groupwise diffeomorphic registration approach to construct a 3D probabilistic atlas that captures the anatomical variability of the MTL. Using serial histology imaging in eleven specimens, we labelled the MTL subregions in the atlas based on cytoarchitecture. Leveraging the atlas and neuropathological ratings of tau and TAR DNA-binding protein 43 (TDP-43) pathology severity, morphometric analysis was performed to correlate regional MTL thickness with the severity of tau pathology, after correcting for age and TDP-43 pathology. We found significant correlations between tau pathology and thickness in the entorhinal cortex (ERC) and stratum radiatum lacunosum moleculare (SRLM). When focusing on cases with low levels of TDP-43 pathology, we found strong associations between tau pathology and thickness in the ERC, SRLM and the subiculum/cornu ammonis 1 (CA1) subfields of the hippocampus, consistent with early Braak stages.
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| 4. |
- Ravikumar, Sadhana, et al.
(författare)
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Improved Segmentation of Deep Sulci in Cortical Gray Matter Using a Deep Learning Framework Incorporating Laplace’s Equation
- 2023
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Ingår i: Information Processing in Medical Imaging - 28th International Conference, IPMI 2023, Proceedings. - 1611-3349 .- 0302-9743. - 9783031340475 ; 13939 LNCS, s. 692-704
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Konferensbidrag (refereegranskat)abstract
- When developing tools for automated cortical segmentation, the ability to produce topologically correct segmentations is important in order to compute geometrically valid morphometry measures. In practice, accurate cortical segmentation is challenged by image artifacts and the highly convoluted anatomy of the cortex itself. To address this, we propose a novel deep learning-based cortical segmentation method in which prior knowledge about the geometry of the cortex is incorporated into the network during the training process. We design a loss function which uses the theory of Laplace’s equation applied to the cortex to locally penalize unresolved boundaries between tightly folded sulci. Using an ex vivo MRI dataset of human medial temporal lobe specimens, we demonstrate that our approach outperforms baseline segmentation networks, both quantitatively and qualitatively.
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| 5. |
- Ravikumar, Sadhana, et al.
(författare)
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Postmortem imaging reveals patterns of medial temporal lobe vulnerability to tau pathology in Alzheimer’s disease
- 2024
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Ingår i: Nature Communications. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Our current understanding of the spread and neurodegenerative effects of tau neurofibrillary tangles (NFTs) within the medial temporal lobe (MTL) during the early stages of Alzheimer’s Disease (AD) is limited by the presence of confounding non-AD pathologies and the two-dimensional (2-D) nature of conventional histology studies. Here, we combine ex vivo MRI and serial histological imaging from 25 human MTL specimens to present a detailed, 3-D characterization of quantitative NFT burden measures in the space of a high-resolution, ex vivo atlas with cytoarchitecturally-defined subregion labels, that can be used to inform future in vivo neuroimaging studies. Average maps show a clear anterior to poster gradient in NFT distribution and a precise, spatial pattern with highest levels of NFTs found not just within the transentorhinal region but also the cornu ammonis (CA1) subfield. Additionally, we identify granular MTL regions where measures of neurodegeneration are likely to be linked to NFTs specifically, and thus potentially more sensitive as early AD biomarkers.
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| 6. |
- Ravikumar, Sadhana, et al.
(författare)
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Unfolding the Medial Temporal Lobe Cortex to Characterize Neurodegeneration Due to Alzheimer’s Disease Pathology Using Ex vivo Imaging
- 2021
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Ingår i: Machine Learning in Clinical Neuroimaging - 4th International Workshop, MLCN 2021, Held in Conjunction with MICCAI 2021, Proceedings. - Cham : Springer International Publishing. - 1611-3349 .- 0302-9743. - 9783030875855 ; 13001 LNCS, s. 3-12
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Konferensbidrag (refereegranskat)abstract
- Neurofibrillary tangle (NFT) pathology in the medial temporal lobe (MTL) is closely linked to neurodegeneration, and is the early pathological change associated with Alzheimer’s Disease (AD). In this work, we investigate the relationship between MTL morphometry features derived from high-resolution ex vivo imaging and histology-based measures of NFT pathology using a topological unfolding framework applied to a dataset of 18 human postmortem MTL specimens. The MTL has a complex 3D topography and exhibits a high degree of inter-subject variability in cortical folding patterns which poses a significant challenge for volumetric registration methods typically used during MRI template construction. By unfolding the MTL cortex, the proposed framework explicitly accounts for the sheet-like geometry of the MTL cortex and provides a two-dimensional reference coordinate space which can be used to implicitly register cortical folding patterns across specimens based on distance along the cortex despite large anatomical variability. Leveraging this framework in a subset of 15 specimens, we characterize the associations between NFTs and morphological features such as cortical thickness and surface curvature and identify regions in the MTL where patterns of atrophy are strongly correlated with NFT pathology.
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| 7. |
- Roh, Hyung S., et al.
(författare)
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Integrating Color Deconvolution Thresholding and Weakly Supervised Learning for Automated Segmentation of Neurofibrillary Tangle and Neuropil Threads
- 2023
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Ingår i: Medical Imaging 2023 : Digital and Computational Pathology - Digital and Computational Pathology. - 1605-7422. - 9781510660472 ; 12471
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Konferensbidrag (refereegranskat)abstract
- Abnormally phosphorylated tau proteins are known to be a major indicator of Alzheimer's Disease (AD) with strong association with memory loss and cognitive decline. Automated generation of pixel-wise accurate neurofibrillary tangles (NFTs) and neuropil threads (NTs) segmentation is a challenging task, due to lack of ground truth segmentation data of these abnormal tau pathology. This problem is most prominent in the case of segmenting NTs, where the small threadlike morphology makes pixel-wise labeling a laborious task and unrealistic for large-scale studies. Lack of ground truth data poses a significant limitation for many learning-based methods to generate accurate segmentations of NFTs and NTs. This work presents an automated pipeline for pixel level segmentation of NFTs and NTs that does not rely on ground truth segmentation data. The pipeline is composed of four main steps: (1) color deconvolution is used to separate histopathology images into staining channels (DAB, Hematoxylin, and Eosin), (2) Otsu's thresholding is used on the DAB stain channel to generate pixel level segmentation of abnormal tau proteins staining, (3) a weakly-supervised learning paradigm (WildCat), using only global descriptors of images, is used to generate density maps of potential regions of NFTs and NTs, and (4) density maps and segmentations are then integrated using connected component analysis to localize NFTs and NTs in the detected tau segmentations. Our results show high global classification accuracy for NFTs (Acc:0.96) and NTs (Acc:0.91), and statistically significant distinctions when evaluating the percent area occupied of the detected NTs relative to expert ratings of NTs severity. Qualitative assessment of the NFTs and NTs results showed accurate pixel-level segmentations of the NFTs, while modest performance for NTs.
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| 8. |
- Zarzo-Arias, Alejandra, et al.
(författare)
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Identifying potential areas of expansion for the endangered brown bear (Ursus arctos) population in the Cantabrian Mountains (NW Spain)
- 2019
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Many large carnivore populations are expanding into human-modified landscapes and the subsequent increase in coexistence between humans and large carnivores may intensify various types of conflicts. A proactive management approach is critical to successful mitigation of such conflicts. The Cantabrian Mountains in Northern Spain are home to the last remaining native brown bear (Ursus arctos) population of the Iberian Peninsula, which is also amongst the most severely threatened European populations, with an important core group residing in the province of Asturias. There are indications that this small population is demographically expanding its range. The identification of the potential areas of brown bear range expansion is crucial to facilitate proactive conservation and management strategies towards promoting a further recovery of this small and isolated population. Here, we used a presence-only based maximum entropy (MaxEnt) approach to model habitat suitability and identify the areas in the Asturian portion of the Cantabrian Mountains that are likely to be occupied in the future by this endangered brown bear population following its range expansion. We used different spatial scales to identify brown bear range suitability according to different environmental, topographic, climatic and human impact variables. Our models mainly show that: (1) 4977 km(2) are still available as suitable areas for bear range expansion, which represents nearly half of the territory of Asturias; (2) most of the suitable areas in the western part of the province are already occupied (77% of identified areas, 2820 km(2)), 41.4% of them occurring inside protected areas, which leaves relatively limited good areas for further expansion in this part of the province, although there might be more suitable areas in surrounding provinces; and (3) in the eastern sector of the Asturian Cantabrian Mountains, 62% (2155 km(2)) of the land was classified as suitable, and this part of the province hosts 44.3% of the total area identified as suitable areas for range expansion. Our results further highlight the importance of increasing: (a) the connectivity between the currently occupied western part of Asturias and the areas of potential range expansion in the eastern parts of the province; and (b) the protection of the eastern sector of the Cantabrian Mountains, where most of the future population expansion may be expected.
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| 9. |
- Penteriani, Vincenzo, et al.
(författare)
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Consequences of brown bear viewing tourism : A review
- 2017
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Ingår i: Biological Conservation. - : Elsevier BV. - 0006-3207 .- 1873-2917. ; 206, s. 169-180
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Forskningsöversikt (refereegranskat)abstract
- Many countries promote wildlife observation as part of ecotourism offerings. The brown bear Ursus arctos is among the most targeted species for ecotourism in Notth America and Europe, making it an ideal candidate to examine the consequences of wildlife viewing upon the species. As bear viewing often occurs in sensitive places where bears congregate for mating, rearing young and/or feeding, it is important to evaluate potential positive and negative effects of different viewing practices. Here we reviewed available information on bear viewing practices and their effects on bears, people and ecosystems. Behavioural, physiological and ecological aspects related to bears are reviewed from three different perspectives: ecotourism consequences for bears, direct bear-human interactions and social impacts of bear ecotourism. Because bear viewing can have positive and negative impacts on both bear populations and bear-human interactions, it is important to carefully evaluate every practice associated with bear viewing at a local scale. Because bear populations around the world have diverse population statuses and different management regimes, successful procedures and rules effective in one place do not guarantee that they will be adequate elsewhere. Effective management of bear viewing practices requires a better understanding of the consequences for bears, the mechanisms behind observed bear reactions to humans, and the results of bear habituation. Because inappropriate beat viewing practices can lead to processes such as food conditioning and habituation, which can have serious consequences for both people and bears, regulations on bear ecotourism are urgently needed to minimize unintended consequences of bear viewing practices.
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| 10. |
- Penteriani, Vincenzo, et al.
(författare)
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Evolutionary and ecological traps for brown bears Ursus arctos in human-modified landscapes
- 2018
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Ingår i: Mammal Review. - : Wiley. - 0305-1838 .- 1365-2907. ; 48:3, s. 180-193
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Forskningsöversikt (refereegranskat)abstract
- Evolutionary traps, and their derivative, ecological traps, occur when animals make maladaptive decisions based on seemingly reliable environmental cues, and are important mechanistic explanations for declines in animal populations. Despite the interest in large carnivore conservation in human-modified landscapes, the emergence of traps and their potential effects on the conservation of large carnivore populations has frequently been overlooked. The brown bear Ursus arctos typifies the challenges facing large carnivore conservation and recent research has reported that this species can show maladaptive behaviours in human-modified landscapes. Here we review, describe and discuss scenarios recognised as evolutionary or ecological traps for brown bears, and propose possible trap scenarios and mechanisms that have the potential to affect the dynamics and viability of brown bear populations. Six potential trap scenarios have been detected for brown bears in human-modified landscapes: 1) food resources close to human settlements; 2) agricultural landscapes; 3) roads; 4) artificial feeding sites; 5) hunting by humans; and 6) other human activities. Because these traps are likely to be of contrasting relevance for different demographic segments of bear populations, we highlight the importance of evaluations of the relative demographic consequences of different trap types for wildlife management. We also suggest that traps may be behind the decreases in brown bear and other large carnivore populations in human-modified landscapes.
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