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| 442. |
- Koefoed-Nielsen, P., et al.
(författare)
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Scandiatransplant acceptable mismatch program (STAMP) a bridge to transplanting highly immunized patients
- 2017
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Ingår i: HLA. - : Wiley. - 2059-2302 .- 2059-2310. ; 90:1, s. 17-24
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Tidskriftsartikel (refereegranskat)abstract
- Background: Highly immunized patients are a challenge for organ transplantation programs. One way of increasing the likelihood of transplantation in this group of patients is to expand the possible donations by defining acceptable HLA mismatches. In the Scandiatransplant Acceptable Mismatch Program (STAMP), a decentralized approach has been implemented in 2009. Aims: The program has been improved during the years from utilizing HLA-A, -B, -DR matching only to include typing of all deceased donors for HLA-A, -B, -C, -DRB1 and -DQB1. The calculation of a transplantability score (TS) has been introduced in order to take both HLA and AB0 into consideration resulting in a more realistic picture of the transplantability chance. Materials and Methods: Patients were selected for eligibility and results of immunisation status were prepared in each of the 9 tissue typing laboratories, while access to the program is finally governed by a common steering group of immunologists and clinicians. Results: In the period from March 2009 until February 2015, 96 patients were transplanted within this program. The mean recipient age was 49 years and 57% were females, 30% of the patients were first transplants and of these 93% were females. The majority of the patients had 2-5 HLA-A, -B. -DR mismatches. The allograft survival at 60 months was 79.1%. Applying the TS to the cohort confirmed that patients with a low TS score had longer waiting times. Conclusion: The program has matured during the years and now proves to be a valid approach for transplanting highly immunized patients.
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| 443. |
- Koriakina, Nadezhda, 1991-, et al.
(författare)
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Visualization of convolutional neural network class activations in automated oral cancer detection for interpretation of malignancy associated changes
- 2019
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Ingår i: 3rd NEUBIAS Conference, Luxembourg, 2-8 February 2019.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Cancer of the oral cavity is one of the most common malignancies in the world. The incidence of oral cavity and oropharyngeal cancer is increasing among young people. It is noteworthy that the oral cavity can be relatively easily accessed for routine screening tests that could potentially decrease the incidence of oral cancer. Automated deep learning computer aided methods show promising ability for detection of subtle precancerous changes at a very early stage, also when visual examination is less effective. Although the biological nature of these malignancy associated changes is not fully understood, the consistency of morphology and textural changes within a cell dataset could shed light on the premalignant state. In this study, we are aiming to increase understanding of this phenomenon by exploring and visualizing what parts of cell images are considered as most important when trained deep convolutional neural networks (DCNNs) are used to differentiate cytological images into normal and abnormal classes.Materials and methods: Cell samples are collected with a brush at areas of interest in the oral cavity and stained according to standard PAP procedures. Digital images from the slides are acquired with a 0.32 micron pixel size in greyscale format (570 nm bandpass filter). Cell nuclei are manually selected in the images and a small region is cropped around each nucleus resulting in images of 80x80 pixels. Medical knowledge is not used for choosing the cells but they are just randomly selected from the glass; for the learning process we are only providing ground truth on the patient level and not on the cell level. Overall, 10274 images of cell nuclei and the surrounding region are used to train state-of-the-art DCNNs to distinguish between cells from healthy persons and persons with precancerous lesions. Data augmentation through 90 degrees rotations and mirroring is applied to the datasets. Different approaches for class activation mapping and related methods are utilized to determine what image regions and feature maps are responsible for the relevant class differentiation.Results and Discussion:The best performing of the observed deep learning architectures reaches a per cell classification accuracy surpassing 80% on the observed material. Visualizing the class activation maps confirms our expectation that the network is able to learn to focus on specific relevant parts of the sample regions. We compare and evaluate our findings related to detected discriminative regions with the subjective judgements of a trained cytotechnologist. We believe that this effort on improving understanding of decision criteria used by machine and human leads to increased understanding of malignancy associated changes and also improves robustness and reliability of the automated malignancy detection procedure.
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| 444. |
- Kraemer, MUG, et al.
(författare)
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Past and future spread of the arbovirus vectors Aedes aegypti and Aedes albopictus
- 2019
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Ingår i: Nature microbiology. - : Springer Science and Business Media LLC. - 2058-5276. ; 4:5, s. 854-863
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Tidskriftsartikel (refereegranskat)abstract
- The global population at risk from mosquito-borne diseases—including dengue, yellow fever, chikungunya and Zika—is expanding in concert with changes in the distribution of two key vectors: Aedes aegypti and Aedes albopictus. The distribution of these species is largely driven by both human movement and the presence of suitable climate. Using statistical mapping techniques, we show that human movement patterns explain the spread of both species in Europe and the United States following their introduction. We find that the spread of Ae. aegypti is characterized by long distance importations, while Ae. albopictus has expanded more along the fringes of its distribution. We describe these processes and predict the future distributions of both species in response to accelerating urbanization, connectivity and climate change. Global surveillance and control efforts that aim to mitigate the spread of chikungunya, dengue, yellow fever and Zika viruses must consider the so far unabated spread of these mosquitos. Our maps and predictions offer an opportunity to strategically target surveillance and control programmes and thereby augment efforts to reduce arbovirus burden in human populations globally.
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| 445. |
- Kraemer, MUG, et al.
(författare)
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Publisher Correction: Past and future spread of the arbovirus vectors Aedes aegypti and Aedes albopictus
- 2019
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Ingår i: Nature microbiology. - : Springer Science and Business Media LLC. - 2058-5276. ; 4:5, s. 900-900
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In the version of this Article originally published, the affiliation for author Catherine Linard was incorrectly stated as ‘6Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK’. The correct affiliation is ‘9Spatial Epidemiology Lab (SpELL), Universite Libre de Bruxelles, Brussels, Belgium’. The affiliation for author Hongjie Yu was also incorrectly stated as ‘11Department of Statistics, Harvard University, Cambridge, MA, USA’. The correct affiliation is ‘15School of Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China’. This has now been amended in all versions of the Article.
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| 446. |
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| 447. |
- Krais, Annette M, et al.
(författare)
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Detection of the fungicide transformation product 4-hydroxychlorothalonil in serum of pregnant women from Sweden and Costa Rica
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Ingår i: Journal of Exposure Science & Environmental Epidemiology. - 1559-064X.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: 4-hydroxychlorothalonil (HCT, R182281), a transformation product of the fungicide chlorothalonil, was recently identified in human serum and breast milk. There are indications that HCT may be more toxic and environmentally persistent than chlorothalonil.OBJECTIVE: Our aim was to investigate serum concentrations of HCT in pregnant women in Sweden and Costa Rica.METHODS: We developed a quantitative analytical method for HCT using liquid chromatography tandem mass spectrometry. We measured HCT in 1808 serum samples from pregnant women from the general population in Sweden (1997-2015) and in 632 samples from 393 pregnant women from an agricultural population in Costa Rica (2010-2011). In Swedish samples, we assessed time trends and investigated seasonality. In the Costa Rican samples, we evaluated variability between and within women and explanatory variables of HCT concentrations.RESULTS: HCT was detected in all serum samples, and the limit of detection was 0.1 µg/L. The median HCT concentration in the Swedish samples was 4.1 µg/L (interquartile range [IQR] of 2.9 - 5.8 µg/L), and 3.9 times higher in the Costa Rican samples (median: 16.1 µg/L; IQR: 10.6 - 25.0 µg/L). We found clear seasonal variation with higher concentrations in the first half of each year among Swedish women. In the Costa Rican study, women working in agriculture and living near banana plantations had higher HCT concentrations, whilst higher parity and having a partner working in agriculture were associated with decreased HCT, and no clear seasonal pattern was observed.IMPACT STATEMENT: For the first time, this study quantifies human exposure to the fungicide chlorothalonil and/or its transformation product 4-hydroxychlorothalonil (HCT, R182281) and finds higher serum concentrations in women from a tropical agricultural setting as compared with women from the general population in Sweden.
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| 448. |
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| 449. |
- Kucerova, Lucie, et al.
(författare)
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Slowed aging during reproductive dormancy is reflected in genome-wide transcriptome changes in Drosophila melanogaster
- 2016
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Background: In models extensively used in studies of aging and extended lifespan, such as C. elegans and Drosophila, adult senescence is regulated by gene networks that are likely to be similar to ones that underlie lifespan extension during dormancy. These include the evolutionarily conserved insulin/IGF, TOR and germ line-signaling pathways. Dormancy, also known as dauer stage in the larval worm or adult diapause in the fly, is triggered by adverse environmental conditions, and results in drastically extended lifespan with negligible senescence. It is furthermore characterized by increased stress resistance and somatic maintenance, developmental arrest and reallocated energy resources. In the fly Drosophila melanogaster adult reproductive diapause is additionally manifested in arrested ovary development, improved immune defense and altered metabolism. However, the molecular mechanisms behind this adaptive lifespan extension are not well understood. Results: A genome wide analysis of transcript changes in diapausing D. melanogaster revealed a differential regulation of more than 4600 genes. Gene ontology (GO) and KEGG pathway analysis reveal that many of these genes are part of signaling pathways that regulate metabolism, stress responses, detoxification, immunity, protein synthesis and processes during aging. More specifically, gene readouts and detailed mapping of the pathways indicate downregulation of insulin-IGF (IIS), target of rapamycin (TOR) and MAP kinase signaling, whereas Toll-dependent immune signaling, Jun-N-terminal kinase (JNK) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways are upregulated during diapause. Furthermore, we detected transcriptional regulation of a large number of genes specifically associated with aging and longevity. Conclusions: We find that many affected genes and signal pathways are shared between dormancy, aging and lifespan extension, including IIS, TOR, JAK/STAT and JNK. A substantial fraction of the genes affected by diapause have also been found to alter their expression in response to starvation and cold exposure in D. melanogaster, and the pathways overlap those reported in GO analysis of other invertebrates in dormancy or even hibernating mammals. Our study, thus, shows that D. melanogaster is a genetically tractable model for dormancy in other organisms and effects of dormancy on aging and lifespan.
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