| 1. |
- Kolbe, Viktor, et al.
(author)
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Indoor Photorealistic 3D Mapping using Stereo Images from SLR Cameras
- 2009
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In: Proceedings of the '09 Swedish Symposium on Image Analysis (SSBA). - Linköping : Linköping University Electronic Press. - 9789163339240
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Conference paper (other academic/artistic)abstract
- Creating a 3D model from photos require an estimate of the position and orientation (pose) of the camera for each photo that is acquired. This paper presents a method to estimate the camera pose using only image data. The images are acquired at a low frequency using a stereo rig, consisting of two rigidly attached SLR cameras. Features are extracted and an optimization problem is solved for each new stereo image. The results are used to merge multiple stereo images and building a larger model of the scene. The accumulated error after processing 10 images can with the present methods be less than 1.2 mm in translation and 0.1 degrees in rotation.
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| 2. |
- Alffenaar, J. W. C., et al.
(author)
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Clinical standards for the dosing and management of TB drugs
- 2022
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In: The International Journal of Tuberculosis and Lung Disease. - Paris, France : International Union Against Tuberculosis and Lung Disease. - 1027-3719 .- 1815-7920. ; 26:6, s. 483-
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Journal article (other academic/artistic)abstract
- Background: Optimal drug dosing is important to ensure adequate response to treatment, prevent development of drug resistance and reduce drug toxicity. The aim of these clinical standards is to provide guidance on 'best practice' for dosing and management of TB drugs.Methods: A panel of 57 global experts in the fields of microbiology, pharmacology and TB care were identified; 51 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all participants.Results: Six clinical standards were defined: Standard 1, defining the most appropriate initial dose for TB treatment; Standard 2, identifying patients who may be at risk of sub-optimal drug exposure; Standard 3, identifying patients at risk of developing drug-related toxicity and how best to manage this risk; Standard 4, identifying patients who can benefit from therapeutic drug monitoring (TDM); Standard 5, highlighting education and counselling that should be provided to people initiating TB treatment; and Standard 6, providing essential education for healthcare professionals. In addition, consensus research priorities were identified.Conclusion: This is the first consensus-based Clinical Standards for the dosing and management of TB drugs to guide clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment to improve patient care.
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| 3. |
- Chandaria, Jigna, et al.
(author)
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Real-Time Camera Tracking in the MATRIS Project
- 2006
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In: Prcoeedings of the 2006 International Broadcasting Convention.
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Conference paper (peer-reviewed)abstract
- In order to insert a virtual object into a TV image, the graphics system needs to know precisely how the camera is moving, so that the virtual object can be rendered in the correct place in every frame. Nowadays this can be achieved relatively easily in postproduction, or in a studio equipped with a special tracking system. However, for live shooting on location, or in a studio that is not specially equipped, installing such a system can be difficult or uneconomic. To overcome these limitations, the MATRIS project is developing a real-time system for measuring the movement of a camera. The system uses image analysis to track naturally occurring features in the scene, and data from an inertial sensor. No additional sensors, special markers, or camera mounts are required. This paper gives an overview of the system and presents some results.
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| 4. |
- Chandaria, Jigna, et al.
(author)
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Real-Time Camera Tracking in the MATRIS Project
- 2007
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In: Smpte Journal. - 0036-1682. ; 116:7-8, s. 266-271
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Journal article (peer-reviewed)abstract
- In order to insert a virtual object into a TV image, the graphics system needs to know precisely how the camera is moving, so that the virtual object can be rendered in the correct place in every frame. Nowadays this can be achieved relatively easily in post-production, or in a studio equipped with a special tracking system. However, for live shooting on location, or in a studio that is not specially equipped, installing such a system can be difficult or uneconomic. To overcome these limitations, the MATRIS project is developing a real-time system for measuring the movement of a camera. The system uses image analysis to track naturally occurring features in the scene, and data from an inertial sensor. No additional sensors, special markers, or camera mounts are required. This paper gives an overview of the system and presents some results.
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| 5. |
- Heyckendorf, Jan, et al.
(author)
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What Is Resistance? Impact of Phenotypic versus Molecular Drug Resistance Testing on Therapy for Multi-and Extensively Drug-Resistant Tuberculosis
- 2018
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In: Antimicrobial Agents and Chemotherapy. - : AMER SOC MICROBIOLOGY. - 0066-4804 .- 1098-6596. ; 62:2
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Journal article (peer-reviewed)abstract
- Rapid and accurate drug susceptibility testing (DST) is essential for the treatment of multi-and extensively drug-resistant tuberculosis (M/XDR-TB). We compared the utility of genotypic DST assays with phenotypic DST (pDST) using Bactec 960 MGIT or Lowenstein-Jensen to construct M/XDR-TB treatment regimens for a cohort of 25 consecutive M/XDR-TB patients and 15 possible anti-TB drugs. Genotypic DST results from Cepheid GeneXpert MTB/RIF (Xpert) and line probe assays (LPAs; Hain GenoType MTBDRplus 2.0 and MTBDRsl 2.0) and whole-genome sequencing (WGS) were translated into individual algorithmderived treatment regimens for each patient. We further analyzed if discrepancies between the various methods were due to flaws in the genotypic or phenotypic test using MIC results. Compared with pDST, the average agreement in the number of drugs prescribed in genotypic regimens ranged from just 49% (95% confidence interval [ CI], 39 to 59%) for Xpert and 63% (95% CI, 56 to 70%) for LPAs to 93% (95% CI, 88 to 98%) for WGS. Only the WGS regimens did not contain any drugs to which pDST showed resistance. Importantly, MIC testing revealed that pDST likely underestimated the true rate of resistance for key drugs (rifampin, levofloxacin, moxifloxacin, and kanamycin) because critical concentrations (CCs) were too high. WGS can be used to rule in resistance even in M/XDR strains with complex resistance patterns, but pDST for some drugs is still needed to confirm susceptibility and construct the final regimens. Some CCs for pDST need to be reexamined to avoid systematic false-susceptible results in low-level resistant isolates.
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| 6. |
- Kalsum, Sadaf, et al.
(author)
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A high content screening assay for discovery of antimycobacterial compounds based on primary human macrophages infected with virulent Mycobacterium tuberculosis
- 2022
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In: Tuberculosis. - : CHURCHILL LIVINGSTONE. - 1472-9792 .- 1873-281X. ; 135
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Journal article (peer-reviewed)abstract
- Drug resistance in Mycobacterium tuberculosis is an emerging threat that makes the discovery of new candidate drugs a priority. In particular, drugs with high sterilizing activity within host cells are needed to improve efficacy and reduce treatment duration. We aimed to develope and validate a High Content Screening assay based on Mycobacterium tuberculosis-infected primary human monocyte-derived macrophages as its natural reservoir. Infected primary human monocyte-derived macrophages were exposed to control antibiotics or tested compounds on 384 well plates. Intracellular bacterial growth and macrophage numbers were evaluated using an ImageXpress High Content Screening system and Z-factor was calculated to assess the reproducibility. The combination of isoniazid and rifampicin as a positive control rendered a Z-factor above 0.4, demonstrating suitability of the assay for screening and compound profiling purposes. In a validation experiment, isoniazid, rifampicin, moxifloxacin and levofloxacin all effectively inhibited intracellular growth as expected. Finally, a pilot screening campaign including 5700 compounds from diverse libraries resulted in the identification of three compounds with confirmed antimycobacterial activity in the low micromolar range and low host cell toxicity. The assay represents an attractive screening platform for both academic research on host-pathogen mechanisms in tuberculosis and for the identification and characterization of novel antimycobacterial compounds.
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| 7. |
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| 8. |
- Köpper, Frederik, et al.
(author)
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Damage-induced DNA replication stalling relies on MAPK-activated protein kinase 2 activity
- 2013
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 110:42, s. 16856-16861
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Journal article (peer-reviewed)abstract
- DNA damage can obstruct replication forks, resulting in replicative stress. By siRNA screening, we identified kinases involved in the accumulation of phosphohistone 2AX (gamma H2AX) upon UV irradiation-induced replication stress. Surprisingly, the strongest reduction of phosphohistone 2AX followed knockdown of the MAP kinase-activated protein kinase 2 (MK2), a kinase currently implicated in p38 stress signaling and G2 arrest. Depletion or inhibition of MK2 also protected cells from DNA damage-induced cell death, and mice deficient for MK2 displayed decreased apoptosis in the skin upon UV irradiation. Moreover, MK2 activity was required for damage response, accumulation of ssDNA, and decreased survival when cells were treated with the nucleoside analogue gemcitabine or when the checkpoint kinase Chk1 was antagonized. By using DNA fiber assays, we found that MK2 inhibition or knockdown rescued DNA replication impaired by gemcitabine or by Chk1 inhibition. This rescue strictly depended on transiesion DNA polymerases. In conclusion, instead of being an unavoidable consequence of DNA damage, alterations of replication speed and origin firing depend on MK2-mediated signaling.
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| 9. |
- Merker, Matthias, et al.
(author)
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Phylogenetically informative mutations in genes implicated in antibiotic resistance in Mycobacterium tuberculosis complex
- 2020
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In: Genome Medicine. - : BMC. - 1756-994X. ; 12:1
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Journal article (peer-reviewed)abstract
- Background A comprehensive understanding of the pre-existing genetic variation in genes associated with antibiotic resistance in the Mycobacterium tuberculosis complex (MTBC) is needed to accurately interpret whole-genome sequencing data for genotypic drug susceptibility testing (DST). Methods We investigated mutations in 92 genes implicated in resistance to 21 anti-tuberculosis drugs using the genomes of 405 phylogenetically diverse MTBC strains. The role of phylogenetically informative mutations was assessed by routine phenotypic DST data for the first-line drugs isoniazid, rifampicin, ethambutol, and pyrazinamide from a separate collection of over 7000 clinical strains. Selected mutations/strains were further investigated by minimum inhibitory concentration (MIC) testing. Results Out of 547 phylogenetically informative mutations identified, 138 were classified as not correlating with resistance to first-line drugs. MIC testing did not reveal a discernible impact of a Rv1979c deletion shared by M. africanum lineage 5 strains on resistance to clofazimine. Finally, we found molecular evidence that some MTBC subgroups may be hyper-susceptible to bedaquiline and clofazimine by different loss-of-function mutations affecting a drug efflux pump subunit (MmpL5). Conclusions Our findings underline that the genetic diversity in MTBC has to be studied more systematically to inform the design of clinical trials and to define sound epidemiologic cut-off values (ECOFFs) for new and repurposed anti-tuberculosis drugs. In that regard, our comprehensive variant catalogue provides a solid basis for the interpretation of mutations in genotypic as well as in phenotypic DST assays.
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| 10. |
- Nakatani, Yoshio, et al.
(author)
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Role of Alanine Racemase Mutations in Mycobacterium tuberculosis D-Cycloserine Resistance
- 2017
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In: Antimicrobial Agents and Chemotherapy. - : AMER SOC MICROBIOLOGY. - 0066-4804 .- 1098-6596. ; 61:12
-
Journal article (peer-reviewed)abstract
- A screening of more than 1,500 drug-resistant strains of Mycobacterium tuberculosis revealed evolutionary patterns characteristic of positive selection for three alanine racemase (Alr) mutations. We investigated these mutations using molecular modeling, in vitro MIC testing, as well as direct measurements of enzymatic activity, which demonstrated that these mutations likely confer resistance to D-cycloserine.
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| 11. |
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| 12. |
- Abate, Ebba, et al.
(author)
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Asymptomatic Helminth Infection in Active Tuberculosis Is Associated with Increased Regulatory and Th-2 Responses and a Lower Sputum Smear Positivity
- 2015
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In: PLoS Neglected Tropical Diseases. - : PUBLIC LIBRARY SCIENCE. - 1935-2727 .- 1935-2735. ; 9:8
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Journal article (peer-reviewed)abstract
- Background The impact of intestinal helminth infection on the clinical presentation and immune response during active tuberculosis (TB) infection is not well characterized. Our aim was to investigate whether asymptomatic intestinal helminth infection alters the clinical signs and symptoms as well as the cell mediated immune responses in patients with active TB.Methodology Consecutive, newly diagnosed TB patients and healthy community controls (CCs) were recruited in North-west Ethiopia. TB-score, body mass index and stool samples were analyzed. Cells from HIV-negative TB patients (HIV-/TB) and from CCs were analyzed for regulatory T-cells (Tregs) and cytokine responses using flow cytometry and ELISPOT, respectively.Results A significantly higher ratio of helminth co-infection was observed in TB patients without HIV (Helm+/HIV-/TB) compared to HIV negative CCs, (40% (121/306) versus 28% (85/306), p = 0.003). Helm+/HIV-/TB patients showed significantly increased IL-5 secreting cells compared to Helm-/HIV-/TB (37 SFU (IQR:13-103) versus 2 SFU (1-50); p = 0.02, n = 30). Likewise, levels of absolute Tregs (9.4 (3.2-16.7) cells/mu l versus 2.4 (1.1-4.0) cells/mu l; p = 0.041) and IL-10 secreting cells (65 SFU (7-196) versus 1 SFU (0-31); p = 0.014) were significantly higher in Helm+/HIV-/TB patients compared to Helm-/HIV-/TB patients. In a multivariate analysis, a lower rate of sputum smear positivity for acid fast bacilli, lower body temperature, and eosinophilia were independently associated with helminth infection in TB patients.Conclusions Asymptomatic helminth infection is associated with increased regulatory T-cell and Th2-type responses and a lower rate of sputum smear positivity. Further studies are warranted to investigate the clinical and immunological impact of helminth infection in TB patients.
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| 13. |
- Abate, E., et al.
(author)
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Effects of albendazole on the clinical outcome and immunological responses in helminth co-infected tuberculosis patients: a double blind randomised clinical trial
- 2015
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In: International Journal of Parasitology. - : Elsevier. - 0020-7519 .- 1879-0135. ; 45:2-3, s. 133-140
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Journal article (peer-reviewed)abstract
- Despite several review papers and experimental studies concerning the impact of chronic helminth infection on tuberculosis in recent years, there is a scarcity of data from clinical field studies in highly endemic areas for these diseases. We believe this is the first randomised clinical trial investigating the impact of albendazole treatment on the clinical and immunological outcomes of helminth co-infected tuberculosis patients. A randomised, double-blind, placebo-controlled trial of albendazole (400 mg per day for 3 days) in helminth-positive tuberculosis patients was conducted in Gondar, Ethiopia. The primary outcome was clinical improvement (Delta TB score) after 2 months. Among secondary outcomes were changes in the levels of eosinophils, CD4+ T cells, regulatory T cells, IFN-gamma, IL-5 and IL-10 after 3 months. A total of 140 helminth co-infected tuberculosis patients were included with an HIV co-infection rate of 22.8%. There was no significant effect on the primary outcome (Delta TB score: 5.6 +/- 2.9 for albendazole versus 5.9 +/- 2.5 for placebo, P = 0.59). The albendazole-treated group showed a decline in eosinophil cells (P = 0.001) and IL-10 (P = 0.017) after 3 months. In an exploratory analysis after 12 weeks, the albendazole treated group showed a trend towards weight gain compared with the placebo group (11.2 +/- 8.5 kg versus 8.2 +/- 8.7 kg, P = 0.08)). The reductions in eosinophil counts and IL-10 show that asymptomatic helminth infection significantly affects host immunity during tuberculosis and can be effectively reversed by albendazole treatment. The clinical effects of helminth infection on chronic infectious diseases such as tuberculosis merit further characterisation. (C) 2014 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.
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| 14. |
- Abate, Ebba, et al.
(author)
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Effects of albendazole treatment on the clinical outcome and immunological responses in patients with helminth infection and pulmonary tuberculosis : a randomized clinical trial
- 2013
-
Other publication (other academic/artistic)abstract
- Background: The impact of helminth infection on the host immune response to tuberculosis (TB) has been characterized in experimental models but less so in the clinical setting. The objective of this study was to investigate the impact of deworming on the clinical outcome and cell mediated immune response in active TB.Methods: Newly diagnosed pulmonary TB patients in Gondar, Ethiopia were examined for helminth infection. Helminth-positive TB patients (W+/TB) were randomized to albendazole (400mg X III per os) or placebo. The primary outcome was change in TB-score after 2 months, and secondary outcomes were sputum smear conversion at the 2nd month, and changes in chest x-ray pattern, CD4+ T-cell count, eosinophil count, IgE-levels and immunological responses after 3 months. In a subset of W+/TB, W-/TB patients and healthy controls, flow cytometry and ELISPOT assays were used to characterize the regulatory T-cell population (Tregs) and the frequency of PPD- stimulated IFN-γ, IL-5 and IL-10 producing peripheral blood mononuclear cells (PBMCs).Results: A total of 140 helminth co-infected TB patients were included with an HIV coinfection rate of 22.8 %. Following albendazole treatment of the W+/TB patients, there was a significant decrease in helminth infection compared to placebo (8% (4/49) vs. 48 % (22/46), p<0.001). No significant effect was observed for albendazole compared to placebo on the primary outcome as evaluated by the TB-score (5.6 ±2.87 vs. 5.87 ±2.54, p=0.59). Eosinophil counts decreased significantly in the albendazole group. In a subgroup analysis of helminthnegative patients following albendazole treatment versus placebo, the albendazole group showed a trend for lower levels of IL-10 producing cells at month three (p=0.08). At baseline, W+/TB patients had a significantly higher mean level of Tregs (% Tregs/CD4+) compared to W-/TB patients and helminth-positive community controls. Additionally, the frequency of IFN-γ, IL-5 and spontaneous IL-10 levels was increased in helminth-positive compared to helminth-negative TB patients.Conclusions: No significant effects on the clinical outcome as measured with the TB-score was detected after albendazole treatment of helminth-positive TB patients compared to placebo. However, significant changes were observed in specific immunological responses such as reduced eosinophil counts and a trend towards lower levels of IL-10 producing cells. At baseline, helminth co-infected TB patients exhibited an increased Treg response as well as an increased IL-5 and spontaneous IL-10 production.
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| 15. |
- Abate, Ebba, et al.
(author)
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Impact of helminth infection on the clinical presentation 1 of pulmonary tuberculosis
- 2013
-
Other publication (other academic/artistic)abstract
- Background: The effects of helminth infection on chronic infectious diseases such as HIV and tuberculosis (TB) merit further characterization. Thus, we assessed the baseline clinical characteristics of helminth infection in patients with active TB in a high endemic area.Methodology: Consecutive, newly diagnosed TB patients were recruited from three health institutions in the north Gondar administrative zone, Ethiopia. Structured questionnaires were used to collect socio-demographic and clinical characteristics. Additionally, the TB score, mid upper arm circumference, body mass index (BMI), BCG vaccination status, stool and sputum microscopy as well as HIV serology and CD4+T cells counts were evaluated.Results: A total of 377 pulmonary TB patients were included in the study. The helminth co infection rate was 33% (123/377) and the most prevalent parasite was Ascaris lumbricoides (53%, 65/123). The HIV co-infection rate was 29% (110/377). Seventy percent (77/110) of the HIV co-infected patients were on anti- retroviral therapy at the time of TB diagnosis. Helminth infection was more prevalent in HIV-negative TB patients compared to HIV-positive TB patients (p=0.025). Smoking and walking bare foot were independently associated to helminth infection in TB patients after adjusting for the influence of HIV. Other than increased eosinophilia, no other significant differences were observed between helminth positive and helminth negative TB patients in the clinical presentation including the TB score, CD4+T-cells, BMI or bacterial load.Conclusion: The clinical presentation of active pulmonary tuberculosis was not affected by helminth infection. Helminth infection was less frequent among HIV-positive TB patients and this finding merits further investigation.
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| 16. |
- Abate, Ebba, et al.
(author)
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The Impact of Asymptomatic Helminth Co-Infection in Patients with Newly Diagnosed Tuberculosis in North-West Ethiopia
- 2012
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In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 7:8
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Journal article (peer-reviewed)abstract
- Background: Areas endemic of helminth infection, tuberculosis (TB) and HIV are to a large extent overlapping. The aim of this study was to assess the impact of asymptomatic helminth infection on the immunological response among TB patients with and without HIV, their house hold contacts and community controls. less thanbrgreater than less thanbrgreater thanMethodology: Consecutive smear positive TB patients (n = 112), their household contacts (n = 71) and community controls (n = 112) were recruited in Gondar town, Ethiopia. Stool microscopy, HIV serology, serum IgE level, eosinophil and CD4 counts were performed and tuberculosis patients were followed up for 3 months after initiation of anti-TB treatment. less thanbrgreater than less thanbrgreater thanResults: Helminth co-infection rate was 29% in TB patients and 21% in both community control and household contacts (p = 0.3) where Ascaris lumbricoides was the most prevalent parasite. In TB patients the seroprevalence of HIV was 47% (53/112). Eosinophilia and elevated IgE level were significantly associated with asymptomatic helminth infection. During TB treatment, the worm infection rate of HIV+/TB patients declined from 31% (10/32) at week 0 to 9% (3/32) at week 2 of TB treatment, whereas HIV2/TB patients showed no change from baseline to week 2, 29% (13/45) vs. 22.2% (10/45). This trend was stable at week 8 and 12 as well. less thanbrgreater than less thanbrgreater thanConclusion: One third of smear positive TB patients were infected with helminths. Eosinophilia and elevated IgE level correlated with asymptomatic worm infection, indicating an effect on host immunity. The rate of worm infection declined during TB treatment in HIV+/TB co-infected patients whereas no decline was seen in HIV2/TB group.
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| 17. |
- Abate, Ebba
(author)
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The impact of helminth infection in patients with active tuberculosis
- 2013
-
Doctoral thesis (other academic/artistic)abstract
- The geographic distribution of helminth infection and tuberculosis (TB) overlap substantially. Experimental animal models and limited data from humans have shown that intestinal helminths could subvert the host immune response towards a T-helper 2 (Th2)-type immune response and an increased regulatory T-cell activity (Tregs). This in turn affects the host's ability to mount an effective Th1 immune-mediated protection against Mycobacterium tuberculosis. However, evidence for this hypothesis in the human setting from helminth infected TB patients is limited. This thesis primarily focuses on the immunological and clinical impact of helminth infection on pulmonary TB. The kinetics of the Quantiferon-Gold (QFN) assay, which measures IFN-³ response to TB-specific antigens in whole blood was assessed and showed a modest decline during TB treatment to the level observed for healthy blood donors. We further assessed another clinical monitoring tool, the-TB-score, composed of clinical signs and symptoms of TB, and found an early decline two weeks after initiation of TB- treatment where a failure of decline correlated with increased mortality. Overall, the helminth co-infection rate was significantly higher in TB patients compared to healthy controls. Helminth co-infection was associated to a significantly higher rate of eosinophilia and IgE-levels in healthy controls and patients with tuberculosis. During the first weeks of anti-TB treatment, a marked decrease in the rate of helminth infection was observed in HIV co-infected compared to HIV-negative TB patients. However, helminth co-infection was more common in HIV negative than HIV positive TB patients. There was no detectable impact of helminth infection on the clinical presentation of pulmonary tuberculosis. At baseline, helminth co-infected TB patients showed an increased frequency of Tregs compared to helminth negative TB patients and healthy controls. This was accompanied by an increased rate of PPD stimulated IL-5 and spontaneous production of IL-10 by peripheral blood mononuclear cells among helminth co-infected TB patients. A placebo controlled randomized trial was conducted in order to test the hypothesis that albendazole treatment of helminth positive TB patients may improve the clinical response of TB by reducing the immunmodulatory effect of helminthes on TB immunity. A total of 140 helminth co-infected TB patients were randomized to albendazole (400 mg per os for three consecutive days) or placebo. No significant difference was observed between the albendazole and placebo group in terms of the primary outcome (TB score change between baseline and week 8). Among the secondary outcomes, a significant decline of peripheral eosinophil cells was observed in the albendazole treated group, but no effect on other outcome variables (changes in chest x-ray findings, IgE level and sputum smear conversion). Regarding the immunological assessment no significant difference was observed for changes in Tregs, and PPD-induced production of IFN- ³ or IL-5 although a non-significant trend of a decrease in IL-10 expressing PBMCs were observed in the albendazole group. Taken together, the burden of helminth infection was higher in TB patients than in a healthy control group. Helminth co-infection during pulmonary TB in the human setting induces an immune response characterized by increased IgE production, eosinophilia as well as increased levels of Tregs and spontaneous IL-10 production. Thus, the immunological impact of helminth infection on the outcome and risk for developing TB merits further investigation.
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| 18. |
- Abate Waktola, Ebba Abate, et al.
(author)
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Polymorphisms in CARD8 and NLRP3 are associated with extrapulmonary TB and poor clinical outcome in active TB in Ethiopia
- 2019
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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 9
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Journal article (peer-reviewed)abstract
- Innate immunity is a first line defense against Mycobacterium tuberculosis infection where inflammasome activation and secretion of the pro-inflammatory cytokine IL-1beta, plays a major role. Thus, genetic polymorphisms in innate immunity-related genes such as CARD8 and NLRP3 may contribute to the understanding of why most exposed individuals do not develop infection. Our aim was to investigate the association between polymorphisms in CARD8 and NLRP3 and active tuberculosis (TB) as well as their relationship to treatment outcome in a high-endemic setting for TB. Polymorphisms in CARD8 (C10X) and NLRP3 (Q705K) were analysed in 1190 TB patients and 1990 healthy donors (HD). There was a significant association between homozygotes in the CARD8 polymorphism and extrapulmonary TB (EPTB), which was not the case for pulmonary TB or HDs. Among TB-patients, there was an association between poor treatment outcome and the NLRP3 (Q705K) polymorphism. Our study shows that inflammasome polymorphisms are associated with EPTB and poor clinical outcome in active TB in Ethiopia. The practical implications and determining causal relationships on a mechanistic level needs further study.
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| 19. |
- Abdalla, Hana, et al.
(author)
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Effects of CNI-1493 on human granulocyte functions
- 2006
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In: Immunobiology. - : Elsevier BV. - 0171-2985 .- 1878-3279. ; 211:3, s. 191-197
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Journal article (peer-reviewed)abstract
- During acute bacterial infections such as sepsis and meningitis, activation of inflammatory mediators such as nitric oxide (NO) plays a crucial role in both pathogenesis and host defense. We have previously reported that CNI-1493, a macrophage deactivator, reduced mortality in infant rats infected with Haemophilus influenzae type b (Hib) with associated decrease in the number of granulocytes in the infected tissue. The aim of the present study was to investigate how CNI-1493 affects granulocytes and macrophages in vitro. Murine macrophages (RAW 264.7) pre-incubated with CNI-1493 prior to activation with lipopolysaccharide (LPS)/interferon gamma (IFNγ) had decreased NO production measured as NO2−/NO3− levels and reduction in inducible NO-synthase (iNOS) expression. Reactive oxygen species (ROS) production was increased in formylmethionyl-leucyl-phenylalanine (FMLP)-stimulated granulocytes following CNI-1493 treatment, whereas F-actin content, motility and chemotaxis were decreased under the same conditions. The effects of CNI-1493 on both NO production in LPS/IFNγ-activated macrophages and ROS production, F-actin content, motility and chemotaxis in granulocytes, may contribute to the reduced inflammatory response and increased survival in Hib-infected animals treated with CNI-1493.
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| 20. |
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| 21. |
- Al Abri, Seif, et al.
(author)
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Tools to implement the World Health Organization End TB Strategy: Addressing common challenges in high and low endemic countries
- 2020
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In: International Journal of Infectious Diseases. - : ELSEVIER SCI LTD. - 1201-9712 .- 1878-3511. ; 92, s. S60-S68
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Journal article (peer-reviewed)abstract
- Aim: The purpose of this viewpoint is to summarize the advantages and constraints of the tools and strategies available for reducing the annual incidence of tuberculosis (TB) by implementing the World Health Organization (WHO) End TB Strategy and the linked WHO TB Elimination Framework, with special reference to Oman. Methods: The case-study was built based on the presentations and discussions at an international workshop on TB elimination in low incidence countries organized by the Ministry of Health, Oman, which took place from September 5 to September 7, 2019, and supported by the WHO and European Society of Clinical Microbiology and Infectious Diseases (ESCMID). Results: Existing tools were reviewed, including the screening of migrants for latent TB infection (LTBI) with interferon-gamma release assays, clinical examination for active pulmonary TB (APTB) including chest X-rays, organization of laboratory services, and the existing centres for mandatory health examination of pre-arrival or arriving migrants, including examination for APTB. The need for public-private partnerships to handle the burden of screening arriving migrants for active TB was discussed at length and different models for financing were reviewed. Conclusions: In a country with a high proportion of migrants from high endemic countries, screening for LTBI is of high priority. Molecular typing and the development of public-private partnerships are needed. (C) 2020 Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.
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| 22. |
- Ancuti, Codruta O., et al.
(author)
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NTIRE 2023 HR NonHomogeneous Dehazing Challenge Report
- 2023
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In: 2023 IEEE/CVF Conference on Computer Vision and Pattern Recognition Workshops (CVPRW). - Vancover : Institute of Electrical and Electronics Engineers (IEEE).
-
Conference paper (peer-reviewed)abstract
- This study assesses the outcomes of the NTIRE 2023 Challenge on Non-Homogeneous Dehazing, wherein novel techniques were proposed and evaluated on new image dataset called HD-NH-HAZE. The HD-NH-HAZE dataset contains 50 high resolution pairs of real-life outdoor images featuring nonhomogeneous hazy images and corresponding haze-free images of the same scene. The nonhomogeneous haze was simulated using a professional setup that replicated real-world conditions of hazy scenarios. The competition had 246 participants and 17 teams that competed in the final testing phase, and the proposed solutions demonstrated the cutting-edge in image dehazing technology.
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| 23. |
- Andersson, Blanka, et al.
(author)
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A novel mycobacterial growth inhibition assay employing live-cell imaging of virulent M. tuberculosis and monitoring of host cell viability
- 2020
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In: Tuberculosis. - : CHURCHILL LIVINGSTONE. - 1472-9792 .- 1873-281X. ; 124
-
Journal article (peer-reviewed)abstract
- Our aim was to develop a Mycobacterium tuberculosis (Mtb) growth inhibition assay (MGIA) as a summary estimate of host immune control of virulent Mtb. Mycobacterial growth inhibition (MGI) using previously frozen human PBMCs infected with H37Rv was assessed by live-cell imaging (Incucyte (c)) complemented by imaging flow cytometry analysis of phagocytosis. MGI measured as relative fluorescence units (RFU) was calibrated to time to positive culture (TTP) in BACTEC 960 MGIT. At a MOI (multiplicity of infection) of 5, there was a wide range of MGI of blood donors (1.1*10(6)-2.7*10(6) RFU, n = 14). Intra- and inter-assay variability were at most 17.5 and 20.7 CV%. Cell viability at day 5 was 57 and 62% monitored by the LDH and Draq7 assays respectively. There was a strong correlation between a readout for Mtb growth using CFU counts or TTP compared to RFU (r2 >= 0.96). Our MGIA enabling live-cell imaging and monitoring of cell viability was able to detect a wide range of Mtb growth inhibition by PBMCs and was calibrated to several readout options for bacterial growth. This MGIA may be valuable as a surrogate marker of host immunity in a personalized medicine approach.
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| 24. |
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| 25. |
- Andersson, Carl, et al.
(author)
-
Deep convolutional networks in system identification
- 2019
-
In: Proc. 58th IEEE Conference on Decision and Control. - : IEEE. - 9781728113982 ; , s. 3670-3676
-
Conference paper (peer-reviewed)abstract
- Recent developments within deep learning are relevant for nonlinear system identification problems. In this paper, we establish connections between the deep learning and the system identification communities. It has recently been shown that convolutional architectures are at least as capable as recurrent architectures when it comes to sequence modeling tasks. Inspired by these results we explore the explicit relationships between the recently proposed temporal convolutional network (TCN) and two classic system identification model structures; Volterra series and block-oriented models. We end the paper with an experimental study where we provide results on two real-world problems, the well-known Silverbox dataset and a newer dataset originating from ground vibration experiments on an F-16 fighter aircraft.
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| 26. |
- Andersson, Carl
(author)
-
Deep learning applied to system identification : A probabilistic approach
- 2019
-
Licentiate thesis (other academic/artistic)abstract
- Machine learning has been applied to sequential data for a long time in the field of system identification. As deep learning grew under the late 00's machine learning was again applied to sequential data but from a new angle, not utilizing much of the knowledge from system identification. Likewise, the field of system identification has yet to adopt many of the recent advancements in deep learning. This thesis is a response to that. It introduces the field of deep learning in a probabilistic machine learning setting for problems known from system identification.Our goal for sequential modeling within the scope of this thesis is to obtain a model with good predictive and/or generative capabilities. The motivation behind this is that such a model can then be used in other areas, such as control or reinforcement learning. The model could also be used as a stepping stone for machine learning problems or for pure recreational purposes.Paper I and Paper II focus on how to apply deep learning to common system identification problems. Paper I introduces a novel way of regularizing the impulse response estimator for a system. In contrast to previous methods using Gaussian processes for this regularization we propose to parameterize the regularization with a neural network and train this using a large dataset. Paper II introduces deep learning and many of its core concepts for a system identification audience. In the paper we also evaluate several contemporary deep learning models on standard system identification benchmarks. Paper III is the odd fish in the collection in that it focuses on the mathematical formulation and evaluation of calibration in classification especially for deep neural network. The paper proposes a new formalized notation for calibration and some novel ideas for evaluation of calibration. It also provides some experimental results on calibration evaluation.
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| 27. |
- Andersson, Carl
(author)
-
Deep probabilistic models for sequential and hierarchical data
- 2022
-
Doctoral thesis (other academic/artistic)abstract
- Consider the problem where we want a computer program capable of recognizing a pedestrian on the road. This could be employed in a car to automatically apply the brakes to avoid an accident. Writing such a program is immensely difficult but what if we could instead use examples and let the program learn what characterizes a pedestrian from the examples. Machine learning can be described as the process of teaching a model (computer program) to predict something (the presence of a pedestrian) with help of data (examples) instead of through explicit programming.This thesis focuses on a specific method in machine learning, called deep learning. This method can arguably be seen as sole responsible for the recent upswing of machine learning in academia as well as in society at large. However, deep learning requires, in human standards, a huge amount of data to perform well which can be a limiting factor. In this thesis we describe different approaches to reduce the amount of data that is needed by encoding some of our prior knowledge about the problem into the model. To this end we focus on sequential and hierarchical data, such as speech and written language.Representing sequential output is in general difficult due to the complexity of the output space. Here, we make use of a probabilistic approach focusing on sequential models in combination with a deep learning structure called the variational autoencoder. This is applied to a range of different problem settings, from system identification to speech modeling.The results come in three parts. The first contribution focus on applications of deep learning to typical system identification problems, the intersection between the two areas and how they can benefit from each other. The second contribution is on hierarchical data where we promote a multiscale variational autoencoder inspired by image modeling. The final contribution is on verification of probabilistic models, in particular how to evaluate the validity of a probabilistic output, also known as calibration.
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| 28. |
- Andersson, Carl R., et al.
(author)
-
Learning deep autoregressive models for hierarchical data
- 2021
-
In: IFAC PapersOnLine. - : Elsevier. - 2405-8963. ; , s. 529-534
-
Conference paper (peer-reviewed)abstract
- We propose a model for hierarchical structured data as an extension to the stochastic temporal convolutional network. The proposed model combines an autoregressive model with a hierarchical variational autoencoder and downsampling to achieve superior computational complexity. We evaluate the proposed model on two different types of sequential data: speech and handwritten text. The results are promising with the proposed model achieving state-of-the-art performance.
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| 29. |
- Andersson Naesseth, Christian, et al.
(author)
-
Capacity estimation of two-dimensional channels using Sequential Monte Carlo
- 2014
-
In: 2014 IEEE Information Theory Workshop. ; , s. 431-435
-
Conference paper (peer-reviewed)abstract
- We derive a new Sequential-Monte-Carlo-based algorithm to estimate the capacity of two-dimensional channel models. The focus is on computing the noiseless capacity of the 2-D (1, ∞) run-length limited constrained channel, but the underlying idea is generally applicable. The proposed algorithm is profiled against a state-of-the-art method, yielding more than an order of magnitude improvement in estimation accuracy for a given computation time.
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| 30. |
- Andersson Naesseth, Christian, et al.
(author)
-
High-Dimensional Filtering Using Nested Sequential Monte Carlo
- 2019
-
In: IEEE Transactions on Signal Processing. - : IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. - 1053-587X .- 1941-0476. ; 67:16, s. 4177-4188
-
Journal article (peer-reviewed)abstract
- Sequential Monte Carlo (SMC) methods comprise one of the most successful approaches to approximate Bayesian filtering. However, SMC without a good proposal distribution can perform poorly, in particular in high dimensions. We propose nested sequential Monte Carlo, a methodology that generalizes the SMC framework by requiring only approximate, properly weighted, samples from the SMC proposal distribution, while still resulting in a correctSMCalgorithm. This way, we can compute an "exact approximation" of, e. g., the locally optimal proposal, and extend the class of models forwhichwe can perform efficient inference using SMC. We showimproved accuracy over other state-of-the-art methods on several spatio-temporal state-space models.
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| 31. |
- Andersson Naesseth, Christian, 1986-
(author)
-
Machine learning using approximate inference : Variational and sequential Monte Carlo methods
- 2018
-
Doctoral thesis (other academic/artistic)abstract
- Automatic decision making and pattern recognition under uncertainty are difficult tasks that are ubiquitous in our everyday life. The systems we design, and technology we develop, requires us to coherently represent and work with uncertainty in data. Probabilistic models and probabilistic inference gives us a powerful framework for solving this problem. Using this framework, while enticing, results in difficult-to-compute integrals and probabilities when conditioning on the observed data. This means we have a need for approximate inference, methods that solves the problem approximately using a systematic approach. In this thesis we develop new methods for efficient approximate inference in probabilistic models.There are generally two approaches to approximate inference, variational methods and Monte Carlo methods. In Monte Carlo methods we use a large number of random samples to approximate the integral of interest. With variational methods, on the other hand, we turn the integration problem into that of an optimization problem. We develop algorithms of both types and bridge the gap between them.First, we present a self-contained tutorial to the popular sequential Monte Carlo (SMC) class of methods. Next, we propose new algorithms and applications based on SMC for approximate inference in probabilistic graphical models. We derive nested sequential Monte Carlo, a new algorithm particularly well suited for inference in a large class of high-dimensional probabilistic models. Then, inspired by similar ideas we derive interacting particle Markov chain Monte Carlo to make use of parallelization to speed up approximate inference for universal probabilistic programming languages. After that, we show how we can make use of the rejection sampling process when generating gamma distributed random variables to speed up variational inference. Finally, we bridge the gap between SMC and variational methods by developing variational sequential Monte Carlo, a new flexible family of variational approximations.
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| 32. |
- Andersson Naesseth, Christian, et al.
(author)
-
Nested Sequential Monte Carlo Methods
- 2015
-
In: Proceedings of The 32nd International Conference on Machine Learning. - : Journal of Machine Learning Research (Online). - 9781510810587 ; , s. 1292-1301
-
Conference paper (peer-reviewed)abstract
- We propose nested sequential Monte Carlo (NSMC), a methodology to sample from sequences of probability distributions, even where the random variables are high-dimensional. NSMC generalises the SMC framework by requiring only approximate, properly weighted, samples from the SMC proposal distribution, while still resulting in a correct SMC algorithm. Furthermore, NSMC can in itself be used to produce such properly weighted samples. Consequently, one NSMC sampler can be used to construct an efficient high-dimensional proposal distribution for another NSMC sampler, and this nesting of the algorithm can be done to an arbitrary degree. This allows us to consider complex and high-dimensional models using SMC. We show results that motivate the efficacy of our approach on several filtering problems with dimensions in the order of 100 to 1 000.
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| 33. |
- Andersson Naesseth, Christian, et al.
(author)
-
Sequential Monte Carlo for Graphical Models
- 2014
-
In: Advances in Neural Information Processing Systems. ; , s. 1862-1870
-
Conference paper (peer-reviewed)abstract
- We propose a new framework for how to use sequential Monte Carlo (SMC) algorithms for inference in probabilistic graphical models (PGM). Via a sequential decomposition of the PGM we find a sequence of auxiliary distributions defined on a monotonically increasing sequence of probability spaces. By targeting these auxiliary distributions using SMC we are able to approximate the full joint distribution defined by the PGM. One of the key merits of the SMC sampler is that it provides an unbiased estimate of the partition function of the model. We also show how it can be used within a particle Markov chain Monte Carlo framework in order to construct high-dimensional block-sampling algorithms for general PGMs.
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| 34. |
- Andersson, Viktoria, et al.
(author)
-
The In vitro Activity of Carbapenems Alone and in Combination with β-lactamase Inhibitors against Difficult-to-treat Mycobacteria; Mycobacterium tuberculosis, Mycobacterium abscessus, and Mycobacterium avium Complex: A Systematic Review
- 2023
-
In: INTERNATIONAL JOURNAL OF MYCOBACTERIOLOGY. - : WOLTERS KLUWER MEDKNOW PUBLICATIONS. - 2212-5531 .- 2212-554X. ; 12:3, s. 211-225
-
Research review (peer-reviewed)abstract
- Difficult-to-treat mycobacterial infections are increasing globally. There is an urgent need of new treatment alternatives for multidrug-resistant Mycobacterium tuberculosis (MTB), as well as nontuberculous mycobacteria such as the Mycobacterium abscessus complex (MABC) and Mycobacterium avium complex (MAC). Recently, new carbapenems and combinations of carbapenems with beta-lactamase inhibitors have become available, but activity data in vitro against mycobacteria are so far scarce. Therefore, we performed a systematic review collating the minimum inhibitory concentrations (MICs) of carbapenems, with or without a beta-lactamase inhibitors for MTB, MABC, and MAC. The databases PubMed and Web of Science were searched for the relevant articles in English up until September 21, 2022. Screening of studies was performed by two independent reviewers. MIC data by recommended methods with at least five individual MICs were included. Data were reported as MIC range, MIC50, modal MIC, and/or histograms when individual MICs were available. The study protocol was registered at PROSPERO (CRD42021258537). After screening, a total of 75 studies with MIC data for carbapenems with or without beta-lactamase inhibitors were included in the review. For MTB, the oral carbapenem tebipenem combined with the beta-lactamase inhibitor clavulanic acid resulted in the most significant reduction of MICs. For MABC, the addition of avibactam to tebipenem resulted in a 64-fold reduction of modal MIC. Data were insufficient for the analysis of MAC. Carbapenems, and in particular the novel oral compound tebipenem, in combination with clavulanic acid for MTB and avibactam for MABC may be an untapped potential for difficult-to-treat mycobacterial infections.
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| 35. |
- Ardeshiri, Tohid, et al.
(author)
-
Bicycle Tracking Using Ellipse Extraction
- 2011
-
In: Proceedings of the 14thInternational Conference on Information Fusion, 2011. - : IEEE. - 9781457702679 ; , s. 1-8
-
Conference paper (peer-reviewed)abstract
- A new approach to track bicycles from imagery sensor data is proposed. It is based on detecting ellipsoids in the images, and treat these pair-wise using a dynamic bicycle model. One important application area is in automotive collision avoidance systems, where no dedicated systems for bicyclists yet exist and where very few theoretical studies have been published. Possible conflicts can be predicted from the position and velocity state in the model, but also from the steering wheel articulation and roll angle that indicate yaw changes before the velocity vector changes. An algorithm is proposed which consists of an ellipsoid detection and estimation algorithm and a particle filter. A simulation study of three critical single target scenarios is presented, and the algorithm is shown to produce excellent state estimates. An experiment using a stationary camera and the particle filter for state estimation is performed and has shown encouraging results.
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| 36. |
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| 37. |
- Axholt, Magnus, et al.
(author)
-
Optical See-Through Head Mounted Display : Direct Linear Transformation Calibration Robustness in the Presence of User Alignment Noise
- 2010
-
In: Proceedings of the 54th Annual Meeting of the Human Factors and Ergonomics Society. - Linköping : Linköping University Electronic Press. - 9780945289371
-
Conference paper (peer-reviewed)abstract
- The correct spatial registration between virtual and real objects in optical see-through augmented reality implies accurate estimates of the user’s eyepoint relative to the location and orientation of the display surface. A common approach is to estimate the display parameters through a calibration procedure involving a subjective alignment exercise. Human postural sway and targeting precision contribute to imprecise alignments, which in turn adversely affect the display parameter estimation resulting in registration errors between virtual and real objects. The technique commonly used has its origin incomputer vision, and calibrates stationary cameras using hundreds of correspondence points collected instantaneously in one video frame where precision is limited only by pixel quantization and image blur. Subsequently the input noise level is several order of magnitudes greater when a human operator manually collects correspondence points one by one. This paper investigates the effect of human alignment noise on view parameter estimation in an optical see-through head mounted display to determine how well astandard camera calibration method performs at greater noise levels than documented in computer vision literature. Through Monte-Carlo simulations we show that it is particularly difficult to estimate the user’s eyepoint in depth, but that a greater distribution of correspondence points in depth help mitigate the effects of human alignment noise.
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| 38. |
- Balcha, Taye, et al.
(author)
-
Detection of lipoarabinomannan in urine for identification of active tuberculosis among HIV-positive adults in Ethiopian health centres
- 2014
-
In: Tropical medicine & international health. - : Wiley. - 1360-2276 .- 1365-3156. ; 19:6, s. 734-742
-
Journal article (peer-reviewed)abstract
- ObjectiveTo assess the diagnostic performance of urine lipoarabinomannan (LAM) detection for TB screening in HIV-positive adults in Ethiopia. MethodsTesting for LAM was performed using the Determine TB-LAM lateral flow assay on urine samples from participants in a prospective cohort with baseline bacteriological categorisation for active TB in sputum. Characteristics of TB patients with regard to LAM status were determined. Participants were followed for 6months to evaluate survival, retention in care and incident TB. ResultsPositive LAM results were found in 78/757 participants. Among 128 subjects with definite (confirmed by culture and/or Xpert MTB/RIF) TB, 33 were LAM-positive (25.8%); the respective figure for clinically diagnosed cases was 2/20 (10%). Five of the remaining 43 LAM-positive individuals had died during the 6-month follow-up period, whereas 38 remained in care without clinical signs of TB. The overall sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 25.8%, 92.9%, 42.3% and 86.0%, respectively. Among TB patients, LAM positivity was associated with higher WHO clinical stage, lower body mass index (BMI), CD4 cell and haemoglobin levels, and with increased mortality. A combination algorithm of urine LAM testing and sputum smear microscopy detected 49 (38.2%) of definite TB cases; among those with CD4 count 100cells/mm(3), this proportion was 66.7%. ConclusionsThe performance of urine LAM testing for TB detection was poor in this population. However, this was improved among subjects with CD4 count 100cells/mm(3). In combination with sputum microscopy urine, LAM could be considered for targeted TB screening in this subgroup.
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| 39. |
- Balcha, Taye, et al.
(author)
-
Intensified Tuberculosis Case-Finding in HIV-Positive Adults Managed at Ethiopian Health Centers: Diagnostic Yield of Xpert MTB/RIF Compared with Smear Microscopy and Liquid Culture
- 2014
-
In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 9:1, s. 85478-
-
Journal article (peer-reviewed)abstract
- Background: Detection of active tuberculosis (TB) before antiretroviral therapy (ART) initiation is important, but optimal diagnostic methods for use in resource-limited settings are lacking. We assessed the prevalence of TB, evaluated the diagnostic yield of Xpert MTB/RIF in comparison with smear microscopy and culture, and the impact of Xpert results on clinical management in HIV-positive adults eligible for ART at health centers in a region of Ethiopia. Methods: Participants were prospectively recruited and followed up at 5 health centers. Trained nurses collected data on socio-demographic characteristics, medical history and symptoms, and performed physical examination. Two paired morning sputum samples were obtained, and lymph node aspirates in case of lymphadenopathy. Diagnostic yield of Xpert MTB/RIF in sputum was compared with smear microscopy and liquid culture. Results: TB was diagnosed in 145/812 participants (17.9%), with bacteriological confirmation in 137 (16.9%). Among bacteriologically confirmed cases, 31 were smear-positive (22.6%), 96 were Xpert-positive (70.1%), and 123 were culture-positive (89.8%). Xpert MTB/RIF increased the TB detection rate by 64 cases (47.4%) compared with smear microscopy. The overall sensitivity of Xpert MTB/RIF was 66.4%, and was not significantly lower when testing one compared with two samples. While Xpert MTB/RIF was 46.7% sensitive among patients with CD4 cell counts greater than200 cells/mm(3), this increased to 82.9% in those with CD4 cell counts less than= 100 cells/mm(3). Compared with Xpert-positive TB patients, Xpert-negative cases had less advanced HIV and TB disease characteristics. Conclusions: Previously undiagnosed TB is common among HIV-positive individuals managed in Ethiopian health centers. Xpert MTB/RIF increased TB case detection, especially in patients with advanced immunosuppression. An algorithm based on the use of a single morning sputum sample for individuals with negative sputum smear microscopy could be considered for intensified case finding in patients eligible for ART. However, technical and cost-effectiveness issues relevant for low-income countries warrant further study.
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| 40. |
- Baumann, Dominik, et al.
(author)
-
On the trade-off between event-based and periodic state estimation under bandwidth constraints
- 2023
-
In: IFAC-PapersOnLine. - : Elsevier. - 2405-8963. ; 56:2, s. 5275-5280
-
Journal article (peer-reviewed)abstract
- Event-based methods carefully select when to transmit information to enable high-performance control and estimation over resource-constrained communication networks. However, they come at a cost. For instance, event-based communication induces a higher computational load and increases the complexity of the scheduling problem. Thus, in some cases, allocating available slots to agents periodically in circular order may be superior. In this article, we discuss, for a specific example, when the additional complexity of event-based methods is beneficial. We evaluate our analysis in a synthetical example and on 20 simulated cart-pole systems.
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| 41. |
- Baumann, Dominik, Ph.D. 1991-, et al.
(author)
-
Safe Reinforcement Learning in Uncertain Contexts
- 2024
-
In: IEEE Transactions on robotics. - : IEEE. - 1552-3098 .- 1941-0468. ; 40, s. 1828-1841
-
Journal article (peer-reviewed)abstract
- When deploying machine learning algorithms in the real world, guaranteeing safety is an essential asset. Existing safe learning approaches typically consider continuous variables, i.e., regression tasks. However, in practice, robotic systems are also subject to discrete, external environmental changes, e.g., having to carry objects of certain weights or operating on frozen, wet, or dry surfaces. Such influences can be modeled as discrete context variables. In the existing literature, such contexts are, if considered, mostly assumed to be known. In this work, we drop this assumption and show how we can perform safe learning when we cannot directly measure the context variables. To achieve this, we derive frequentist guarantees for multiclass classification, allowing us to estimate the current context from measurements. Furthermore, we propose an approach for identifying contexts through experiments. We discuss under which conditions we can retain theoretical guarantees and demonstrate the applicability of our algorithm on a Furuta pendulum with camera measurements of different weights that serve as contexts.
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| 42. |
- Bewket, Gezahegn, et al.
(author)
-
Helminth species dependent effects on Th1 and Th17 cytokines in active tuberculosis patients and healthy community controls
- 2022
-
In: PLoS Neglected Tropical Diseases. - : PUBLIC LIBRARY SCIENCE. - 1935-2727 .- 1935-2735. ; 16:8
-
Journal article (peer-reviewed)abstract
- Despite that the impact of different helminth species is not well explored, the current dogma states that helminths affect the Th1/Th2 balance which in turn affects the risk of tuberculosis (TB) reactivation and severity of disease. We investigated the influence of helminth species on cytokine profiles including IL-17A in TB patients and healthy community controls (CCs). In total, 104 newly diagnosed pulmonary TB patients and 70 HIV negative and Quanti-FERON negative CCs in Gondar, Ethiopia were included following helminth screening by stool microscopy. Plasma samples and ex vivo stimulation of peripheral blood mononuclear cells (PBMCs) with purified protein derivative (PPD) and Staphylococcus enterotoxin B (SEB) was used to determine cytokine profiles by cytometric bead array. In CCs, Ascaris lumbricoides or Schistosoma mansoni infections were associated with an impaired Th1-type response (IFN-gamma, IL-6 and TNF-alpha) in PBMCs mainly with SEB stimulations, whereas in TB patients only hookworm infection showed a similar pattern. Among CCs, the IL-17A response in PBMCs stimulated with SEB was higher only for S. mansoni, whereas in TB patients, the elevated systemic IL-17A plasma level was significantly suppressed in hookworm infected TB patients compared to patients without helminth coinfection. Following treatment of TB and helminth infection there was a general decrease in ex vivio IL-10 and TNF-alpha production in unstimulated, PPD or SEB stimulated PBMCs that was the most pronounced and significant in TB patients infected with S. mansoni, whereas the follow-up levels of IFN-gamma and IL-17A was significantly increased only in TB patients without helminth coinfection from PBMCs stimulated mainly with SEB. In summary, in addition to confirming helminth specific effects on the Th1/Th2 response before and after TB treatment, our novel finding is that IL-17A was impaired in helminth infected TB patients especially for hookworm, indicating a helminth species-specific immunoregulatory effect on IL-17A which needs to be further investigated.
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| 43. |
- Bewket, Gezahegn, et al.
(author)
-
Helminth species specific expansion and increased TNF-alpha production of non-classical monocytes during active tuberculosis
- 2021
-
In: PLoS Neglected Tropical Diseases. - : Public Library of Science. - 1935-2727 .- 1935-2735. ; 15:3
-
Journal article (peer-reviewed)abstract
- Author summary Monocytes are important cells for the early innate immune response and play an integral part during inflammation and infection. Classical monocytes, the dominant monocyte subset during homeostasis and health, have been linked to efficient TB protection. Intermediate or non-classical monocytes have instead been associated with uncontrolled inflammation (TNF-alpha), cell death, and poor protection against Mycobacterium tuberculosis. In areas endemic for intestinal helminths, the immunoregulatory effects of monocytes may affect development or progression of TB disease. The role of monocyte subsets during helminth/TB coinfection have not been studied. In Gondar, Ethiopia, we show that in patients with helminth infection, a helminth species dependent expansion of non-classical monocytes is triggered, where Ascaris and hookworm had the strongest effect in coinfected pulmonary TB-patients. The increase in non-classical monocytes was mainly detected in coinfected patients with a low-to-intermediate disease severity. Only coinfection with helminths and TB induced an increased TNF-alpha response in monocytes. Thus, we found a helminth species-specific dysregulation of monocyte subset distribution and functionality in coinfected TB-patients which could affect TB pathogenesis. Both Mycobacterium tuberculosis infection and helminths may affect innate immune mechanisms such as differential effects on monocytes towards the non-classical and intermediate subsets that favor bacterial persistence. Our aim, was to investigate helminth species specific effects on the frequency and functional activity of monocyte subsets in patients with active tuberculosis and healthy subjects. HIV-negative patients with active pulmonary tuberculosis (PTB) and community controls (CCs) in Gondar, Ethiopia were screened for helminth infection by stool microscopy. Flow cytometric analysis of peripheral blood mononuclear cells (PBMCs) and ex vivo stimulation with purified protein derivative (PPD) and helminth antigens were used to characterize the distribution of monocyte subsets and their function. A total of 74 PTB patients and 57 CCs with and without helminth infection were included. Non-classical monocytes were increased in PTB patients with Ascaris and hookworm infection but not in Schistosoma-infected patients. Ascaris had the strongest effect in increasing the frequency of non-classical monocytes in both PTB patients and CCs, whereas PTB without helminth infection did not affect the frequency of monocyte subsets. There was a helminth specific increase in the frequency of TNF-alpha producing non-classical monocytes in hookworm infected PTB patients, both with and without PPD-stimulation. Low-to-intermediate TB disease severity associated with increased frequency of non-classical monocytes only for helminth-positive PTB patients, and the frequency of TNF-alpha producing monocytes were significantly higher in intermediate and non-classical monocytes of helminth positive PTB patients with an intermediate disease score. Helminth infection affected the frequency of monocyte subsets and function both in TB patients and controls which was helminth species dependent in TB patients. The clinical role of this potential immunomodulatory effect needs further study and may affect the response and protection to tuberculosis in areas where helminth infections are endemic.
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| 44. |
- Bijl, Hildo, et al.
(author)
-
Mean and variance of the LQG cost function
- 2016
-
In: Automatica. - : Elsevier BV. - 0005-1098 .- 1873-2836. ; 67, s. 216-223
-
Journal article (peer-reviewed)abstract
- Linear Quadratic Gaussian (LQG) systems are well-understood and methods to minimize the expected cost are readily available. Less is known about the statistical properties of the resulting cost function. The contribution of this paper is a set of analytic expressions for the mean and variance of the LQG cost function. These expressions are derived using two different methods, one using solutions to Lyapunov equations and the other using only matrix exponentials. Both the discounted and the non-discounted cost function are considered, as well as the finite-time and the infinite-time cost function. The derived expressions are successfully applied to an example system to reduce the probability of the cost exceeding a given threshold.
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| 45. |
- Bijl, Hildo, et al.
(author)
-
Optimal controller/observer gains of discounted-cost LQG systems
- 2019
-
In: Automatica. - : Elsevier. - 0005-1098 .- 1873-2836. ; 101, s. 471-474
-
Journal article (peer-reviewed)abstract
- The linear-quadratic-Gaussian (LQG) control paradigm is well-known in literature. The strategy of minimizing the cost function is available, both for the case where the state is known and where it is estimated through an observer. The situation is different when the cost function has an exponential discount factor, also known as a prescribed degree of stability. In this case, the optimal control strategy is only available when the state is known. This paper builds onward from that result, deriving an optimal control strategy when working with an estimated state. Expressions for the resulting optimal expected cost are also given.
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| 46. |
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| 47. |
- Broman, David, 1977-
(author)
-
Meta-Languages and Semantics for Equation-Based Modeling and Simulation
- 2010
-
Doctoral thesis (other academic/artistic)abstract
- Performing computational experiments on mathematical models instead of building and testing physical prototypes can drastically reduce the develop cost for complex systems such as automobiles, aircraft, and powerplants. In the past three decades, a new category of equation-based modeling languages has appeared that is based on acausal and object-oriented modeling principles, enabling good reuse of models. However, the modeling languages within this category have grown to be large and complex, where the specifications of the language's semantics are informally defined, typically described in natural languages. The lack of a formal semantics makes these languages hard to interpret unambiguously and to reason about. This thesis concerns the problem of designing the semantics of such equation-based modeling languages in a way that allows formal reasoning and increased correctness. The work is presented in two parts.In the first part we study the state-of-the-art modeling language Modelica. We analyze the concepts of types in Modelica and conclude that there are two kinds of type concepts: class types and object types. Moreover, a concept called structural constraint delta is proposed, which is used for isolating the faults of an over- or under-determined model.In the second part, we introduce a new research language called the Modeling Kernel Language (MKL). By introducing the concept of higher-order acausal models (HOAMs), we show that it is possible to create expressive modeling libraries in a manner analogous to Modelica, but using a small and simple language concept. In contrast to the current state-of-the-art modeling languages, the semantics of how to use the models, including meta operations on models, are also specified in MKL libraries. This enables extensible formal executable specifications where important language features are expressed through libraries rather than by adding completely new language constructs. MKL is a statically typed language based on a typed lambda calculus. We define the core of the language formally using operational semantics and prove type safety. An MKL interpreter is implemented and verified in comparison with a Modelica environment.
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| 48. |
- Bånkestad, Maria, et al.
(author)
-
Variational Elliptical Processes
- 2023
-
In: Transactions on Machine Learning Research. - 2835-8856.
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Journal article (peer-reviewed)abstract
- We present elliptical processes—a family of non-parametric probabilistic models that subsumes Gaussian processes and Student's t processes. This generalization includes a range of new heavy-tailed behaviors while retaining computational tractability. Elliptical processes are based on a representation of elliptical distributions as a continuous mixture of Gaussian distributions. We parameterize this mixture distribution as a spline normalizing flow, which we train using variational inference. The proposed form of the variational posterior enables a sparse variational elliptical process applicable to large-scale problems. We highlight advantages compared to Gaussian processes through regression and classification experiments. Elliptical processes can supersede Gaussian processes in several settings, including cases where the likelihood is non-Gaussian or when accurate tail modeling is essential.
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| 49. |
- Carlsson, Håkan, et al.
(author)
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Quantifying the Uncertainty of the Relative Geometry in Inertial Sensors Arrays
- 2021
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In: IEEE Sensors Journal. - : Institute of Electrical and Electronics Engineers (IEEE). - 1530-437X .- 1558-1748. ; 21:17, s. 19362-19373
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Journal article (peer-reviewed)abstract
- We present an algorithm to estimate and quantify the uncertainty of the accelerometers' relative geometry in an inertial sensor array. We formulate the calibration problem as a Bayesian estimation problem and propose an algorithm that samples the accelerometer positions' posterior distribution using Markov chain Monte Carlo. By identifying linear substructures of the measurement model, the unknown linear motion parameters are analytically marginalized, and the remaining non-linear motion parameters are numerically marginalized. The numerical marginalization occurs in a low dimensional space where the gyroscopes give information about the motion. This combination of information from gyroscopes and analytical marginalization allows the user to make no assumptions of the motion before the calibration. It thus enables the user to estimate the accelerometer positions' relative geometry by simply exposing the array to arbitrary twisting motion. We show that the calibration algorithm gives good results on both simulated and experimental data, despite sampling a high dimensional space.
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| 50. |
- Carney, Rebecca
(author)
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Instrumentation for silicon tracking at the HL-LHC
- 2017
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Licentiate thesis (other academic/artistic)abstract
- In 2027 the Large Hadron Collider (LHC) at CERN will enter a high luminosity phase, deliver- ing 3000 fb 1 over the course of ten years. The High Luminosity LHC (HL-LHC) will increase the instantaneous luminosity delivered by a factor of 5 compared to the current operation pe- riod. This will impose significant technical challenges on all aspects of the ATLAS detector but particularly the Inner Detector, trigger, and data acquisition systems. In addition, many of the components of the Inner Detector are reaching the end of their designed lifetime and will need to be exchanged. As such, the Inner Detector will be entirely replaced by an all silicon tracker, known as the Inner Tracker (ITk).The layout of the Pixel and strip detectors will be optimised for the upgrade and will extend their forward coverage. To reduce the per-pixel hit rate and explore novel techniques for deal- ing with the conditions in HL-LHC, an inter-experiment collaboration called RD53 has been formed. RD53 is tasked with producing a front-end readout chip to be used as part of hybrid Pixel detectors that can deal with the high multiplicity environment in the HL-LHC.A silicon sensor, which makes up the other half of the hybrid Pixel detector, must also be designed to cope with the high fluences in HL-LHC. Significant damage will be caused by non- ionising energy loss in the sensor over its lifetime. This damage must be incorporated into the detector simulation both to predict the detector performance at specific conditions and to understand the e↵ects of radiation damage on data taking. The implementation of radiation damage in the ATLAS simulation framework is discussed in this thesis.Collisions produced by the HL-LHC also presents a challenge for the current track reconstruc- tion software. High luminosity is obtained, in part, by increasing the number of interactions per bunch crossing, which in turn increases the time taken for track reconstruction. Various ap- proaches to circumvent the strain on projected resources are being explored, including porting existing algorithms to parallel architectures. A popular algorithm used in track reconstruction, the Kalman filter, has been implemented in a neuromorphic architecture: IBM’s TrueNorth. The limits of using such an architecture for tracking, as well as how its performance compares to a non-spiking Kalman filter implementation, are explored in this thesis.
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