| 1. |
- Pearce, Neil E, et al.
(författare)
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IARC Monographs : 40 Years of Evaluating Carcinogenic Hazards to Humans
- 2015
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 123:6, s. 507-514
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recently the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also the approach used to perform these evaluations. Some critics have claimed that IARC Working Groups' failures to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans.OBJECTIVES: The authors of this paper are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We have examined here criticisms of the IARC classification process to determine the validity of these concerns. We review the history of IARC evaluations and describe how the IARC evaluations are performed.DISCUSSION: We conclude that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various discipline and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed.CONCLUSIONS: The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public's health.
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| 2. |
- Sjöberg, Mats, 1965-, et al.
(författare)
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Infliximab or cyclosporine as rescue therapy in hospitalized patients with steroid-refractory ulcerative colitis : a retrospective observational study
- 2012
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Ingår i: Inflammatory Bowel Diseases. - : John Wiley & Sons. - 1078-0998 .- 1536-4844. ; 18:2, s. 212-218
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cyclosporine (CsA) or infliximab (IFX) are used as rescue therapies in steroid-refractory, severe attacks of ulcerative colitis (UC). There are no data comparing the efficacy of these two alternatives. Methods: Outcome of rescue therapy was retrospectively studied in two cohorts of patients hospitalized due to steroid-refractory moderate to severe UC: 1) a Swedish-Danish cohort (n 49) treated with a single infusion of IFX; 2) an Austrian cohort (n 43) treated with intravenous CsA. After successful rescue therapy, maintenance immunomodulator treatment was given to 27/33 (82%) of IFX patients and to 31/40 (78%) of CsA patients. Endpoints were colectomy-free survival at 3 and 12 months. Kaplan-Meier and Cox regression models were used to evaluate the association between treatment groups and colectomy. Results: At 15 days, colectomy-free survival in the IFX cohort was 36/49 (73%) versus 41/43 (95%) in the CsA cohort (P = 0.005), at 3 months 33/49 (67%) versus 40/43 (93%) (P = 0.002), and at 12 months 28/49 (57%) versus 33/43 (77%) (P = 0.034). After adjusting for potential confounding factors, Cox regression analysis yielded adjusted hazard ratios for risk of colectomy in IFX-treated patients of 11.2 (95% confidence interval [CI] 2.4-53.1, P = 0.002) at 3 months and of 3.0 (95% CI 1.1-8.2, P = 0.030) at 12 months in comparison with CsA-treated patients. There were no opportunistic infections or mortality. Conclusions: Colectomy frequencies were significantly lower after rescue therapy with CsA than with a single infusion of IFX both at 3 and 12 months' follow-up. The superiority of CsA was seen principally during the first 15 days.
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| 3. |
- Amorim, Joni A., et al.
(författare)
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Augmented Reality and Mixed Reality Technologies : Enhancing Training and Mission Preparation with Simulations
- 2013
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Konferensbidrag (refereegranskat)abstract
- The Instruction Centre for Operations on Law and Order Assurance (CIOpGLO) is a Brazilian Army facility created in March 2005 in Campinas, Brazil. The mission of this centre involves the offering of training in different perspectives, which includes the preparation of soldiers to enter in slums areas in Rio de Janeiro and other cities to arrest criminals, whenever a federal intervention is required. This centre is involved in training to guarantee law and order and, at the same time, prepare officers and soldiers for interventions even in urban areas. To allow such training, this facility counts with physical built sites to allow soldiers to train how to get inside houses, how to shoot at short ranges (from 0 to 30 meters), how to move and shelter while going up in a hill with many houses and corridors on the way, and so on. The Brazilian Army, in the last few years, started operating in slums like the ones of the "Alemão" and the "Penha" complex in Rio de Janeiro. The Army is also participating in operations out of Brazil in countries like Haiti. In situations like this, the armed forces take over the coordination of public security temporarily to recover the control of certain areas. Since the armed forces were not originally created to act in situations like this, there is a need to train all military stakeholders involved so that the operations are successful. Additionally, major events like the Confederations Cup, the World Cup in 2014 and the Olympics in 2016, generate additional demands for the armed forces, which are likely to be called to act at specific times. Moreover, it is noteworthy that there is a growing trend in which conflicts around the world occur, more than ever, inside the cities, where civilians take great risk and suffer many casualties, something called as “collateral damage” of the urban warfare. Recent examples include Afghanistan and Iraq. In this work, the preparation of soldiers at CIOpGLO is discussed while the possibility of using new approaches based on augmented reality and mixed reality technologies are considered. As a way to enhance training and mission preparation with simulations, this research focus on augmented reality (AR) supported by head-mounted displays (HMDs). HDMs may have many shapes, which include pairs of glasses with lenses that present AR with superposed images, enabling its wearer a total immersion in the simulation. The method used in this work involves a literature review on AR and HMDs, assessment of training needs at the Brazilian Army and an evaluation of emerging technologies from the ICT sector. The technologies to be considered are the HDMs, in this specific case the available programming languages, software and hardware from suppliers of commercial off-the-shelf (COTS) and military off-the-shelf (MOTS). The main contribution of this work is the comparative study of the main solutions for HDM. This study represents an essential step for concept development and for the experimentation to exploit and evaluate the use of simulations. The research presented suggests that the approach is effective and that future work should be on both development of new applications and its evaluation in real training sets in Brazil.
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| 4. |
- Blais, Curtis, et al.
(författare)
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Design and Development of an Architecture for Demonstrating the Interplay of Emerging SISO Standards
- 2007
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Ingår i: Simulation Interoperability Standards Organization - Spring Simulation Interoperability Workshop 2007, 07 Spring SIW. - 9781604239232 ; , s. 302-309
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Konferensbidrag (refereegranskat)abstract
- The Simulation Interoperability Standards Organization (SISO) focuses on facilitating simulation interoperability across government and non-government applications worldwide. A number of standards are emerging that will individually have great impact on the development and operation of simulation systems, as well as interoperation across simulation systems and command and control systems. Taken together, however, the emerging standards represent a set of capabilities and technologies which can revolutionize the simulation industry, radically improving the way we develop and deliver interoperable systems.In the Fall 2006 Simulation Interoperability Workshop, an architecture for demonstrating the interplay of several current and emerging SISO standards was presented. The following standards were selected for development of an initial demonstration system: (1) the Coalition Battle Management Language (C-BML) for unambiguous expression of plans and orders for live, constructive, and robotic forces; (2) the Military Scenario Definition Language (MSDL) for describing a scenarios that can be shared across multiple systems; (3) Base Object Models (BOMs) for specifying building blocks for composing larger model sets; (4) the Simulation Reference Markup Language (SRML) for platform-independent representation of executable behavior models; and (5) the Distributed Interactive Simulation Extensible Markup Language (DIS-XML) initiative for representing DIS Protocol Data Units in XML to enhance interchange of dynamic entity state and entity interactions across diverse systems in web-based network centric architectures.This paper discusses how the framework can be used by the SISO community as a means for educating the community on emerging standards and as a platform for demonstration of new concepts and capabilities as a precursor to a new standardization effort. It describes work performed to design and develop an initial test case demonstrating the integration of these standards, including problems encountered, problem resolutions, lessons learned, and future work.
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| 5. |
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| 6. |
- Gustavsson, Anders, et al.
(författare)
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Clinical trial : colectomy after rescue therapy in ulcerative colitis-3-year follow-up of the Swedish-Danish controlled infliximab study
- 2010
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 32:8, s. 984-989
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Tidskriftsartikel (refereegranskat)abstract
- Background The long-term efficacy of infliximab as rescue therapy in steroid-refractory ulcerative colitis is not well described. Aim To examine the long-term efficacy of infliximab as a rescue therapy through a 3-year follow-up of a previous placebo-controlled trial of infliximab in acute steroid-refractory ulcerative colitis. Method In the original study, 45 patients were randomized to a single infusion of infliximab 5 mg/kg or placebo, and at 3 months, 7/24 patients given infliximab were operated vs. 14/21 patients given placebo. Three years or later, patients were asked to participate in a clinical follow-up. Results Another seven patients underwent colectomy during follow-up: five in the infliximab group and two in the placebo group. After 3 years, a total of 12/24 (50%) patients given infliximab and 16/21 (76%) given placebo (P = 0.012) had a colectomy. None of eight patients in endoscopic remission at 3 months later had a colectomy compared with 7/14 (50%) patients who were not in remission (P = 0.02). There was no mortality. Conclusion The benefit of rescue therapy with infliximab in steroid-refractory acute ulcerative colitis remained after 3 years. The main advantage of infliximab treatment occurred during the first 3 months, whereas subsequent colectomy rates were similar in the two groups. Mucosal healing at 3 months influenced later risk of colectomy.
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| 7. |
- Niklasson, Mia, et al.
(författare)
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Membrane-Depolarizing Channel Blockers Induce Selective Glioma Cell Death by Impairing Nutrient Transport and Unfolded Protein/Amino Acid Responses
- 2017
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Ingår i: Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 77:7, s. 1741-1752
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Tidskriftsartikel (refereegranskat)abstract
- Glioma-initiating cells (GIC) are considered the underlying cause of recurrences of aggressive glioblastomas, replenishing the tumor population and undermining the efficacy of conventional chemotherapy. Here we report the discovery that inhibiting T-type voltage-gated Ca2+ and KCa channels can effectively induce selective cell death of GIC and increase host survival in an orthotopic mouse model of human glioma. At present, the precise cellular pathways affected by the drugs affecting these channels are unknown. However, using cell-based assays and integrated proteomics, phosphoproteomics, and transcriptomics analyses, we identified the downstreamsignaling events these drugs affect. Changes in plasma membrane depolarization and elevated intracellular Na+, which compromised Na+-dependent nutrient transport, were documented. Deficits in nutrient deficit acted in turn to trigger the unfolded protein response and the amino acid response, leading ultimately to nutrient starvation and GIC cell death. Our results suggest new therapeutic targets to attack aggressive gliomas.
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| 8. |
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| 9. |
- Ahlin, Gustav, et al.
(författare)
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Structural requirements for drug inhibition of the liver specific human organic cation transport protein 1
- 2008
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 51:19, s. 5932-5942
-
Tidskriftsartikel (refereegranskat)abstract
- The liver-specific organic cation transport protein (OCT1; SLC22A1) transports several cationic drugs including the antidiabetic drug metformin and the anticancer agents oxaliplatin and imatinib. In this study, we explored the chemical space of registered oral drugs with the aim of studying the inhibition pattern of OCT1 and of developing predictive computational models of OCT1 inhibition. In total, 191 structurally diverse compounds were examined in HEK293-OCT1 cells. The assay identified 47 novel inhibitors and confirmed 15 previously known inhibitors. The enrichment of OCT1 inhibitors was seen in several drug classes including antidepressants. High lipophilicity and a positive net charge were found to be the key physicochemical properties for OCT1 inhibition, whereas a high molecular dipole moment and many hydrogen bonds were negatively correlated to OCT1 inhibition. The data were used to generate OPLS-DA models for OCT1 inhibitors; the final model correctly predicted 82% of the inhibitors and 88% of the noninhibitors of the test set.
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| 10. |
- Alhamdow, Ayman, et al.
(författare)
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DNA-methylation of the cancer-related genes F2RL3 and AHRR is associated with occupational exposure to polycyclic aromatic hydrocarbons
- 2018
-
Ingår i: Carcinogenesis. - : Oxford University Press. - 0143-3334 .- 1460-2180. ; 39:7, s. 869-878
-
Tidskriftsartikel (refereegranskat)abstract
- Some polycyclic aromatic hydrocarbons (PAH) are known carcinogens and workplace PAH exposure may increase the risk of cancer. Monitoring early cancer-related changes can indicate whether the exposure is carcinogenic. Here, we enrolled 151 chimney sweeps, 152 controls, and 19 creosote-exposed male workers from Sweden. We measured urinary PAH metabolites using LC/MS/MS, the cancer-related markers telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) using qPCR, and DNA methylation of lung cancer-related genes F2RL3 and AHRR using pyrosequencing. The median 1-hydroxypyrene (PAH metabolite) concentrations were highest in creosote-exposed workers (8.0 μg/g creatinine) followed by chimney sweeps (0.34 μg/g creatinine) and controls (0.05 μg/g creatinine). TL and mtDNAcn did not differ between study groups. Chimney sweeps and creosote-exposed workers had significantly lower methylation of AHRR CpG site cg05575921 (88.1% and 84.9%, respectively) than controls (90%). Creosote-exposed workers (73.3%), but not chimney sweeps (76.6%) had lower methylation of F2RL3 cg03636183 than controls (76.7%). Linear regression analyses showed that chimney sweeps had lower AHRR cg05575921 methylation (B=-2.04; P<0.057, adjusted for smoking and age) and lower average AHRR methylation (B=-2.05; P<0.035), and non-smoking chimney sweeps had lower average F2RL3 methylation (B=-0.81; P<0.042, adjusted for age) compared with controls. These cancer-related markers were not associated with urinary concentrations of PAH metabolites. In conclusion, although we found no associations with PAH metabolites in urine (short-term exposure), our results suggest dose-response relationship between PAH exposure and DNA hypomethylation of lung cancer-related loci. These findings indicate that further protective measures should be taken to reduce PAH exposure.
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| 11. |
- Amorim, Joni A., et al.
(författare)
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Awareness and training : Identification of relevant security skills and competencies
- 2014
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Ingår i: Engineering Education in a Technology-Dependent World. - Guimarães : INTERTECH. - 9788565992282 - 9788566680287 ; , s. 37-
-
Konferensbidrag (refereegranskat)abstract
- In order to identify needed skills and competencies for privacy and security, we propose a systematic process that maps privacy and security threats to related controls that are required to prevent, detect or remove such threats. This work suggests how to apply the process, while discussing how games and simulations can be used both to develop the desired behavior and to monitor the current competency level.
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| 12. |
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| 13. |
- Amorim, Joni A., et al.
(författare)
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Cyber Security Training Perspectives
- 2013
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Konferensbidrag (refereegranskat)abstract
- Building comprehensive cyber security strategies to protect people, infrastructure and assets demands research on methods and practices to reduce risks. Once the methods and practices are identified, there is a need to develop training for the manystakeholders involved, from security experts to the end user. In thispaper, we discuss new approaches for training, which includes the development of serious games for training on cyber security. The identification of the theoretical framework to be used for situation and threat assessment receives special consideration.
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| 14. |
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| 15. |
- Amorim, Joni A., et al.
(författare)
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Privacy and Security in Cyberspace : Training Perspectives on the Personal Data Ecosystem
- 2013
-
Ingår i: European Intelligence and Security Informatics Conference (EISIC), Proceedings CD. - : IEEE conference proceedings. - 9780769550626 ; , s. 139-142
-
Konferensbidrag (refereegranskat)abstract
- There is a growing understanding that privacy is an essential component of security. In order to decrease the probability of having data breaches, the design of information systems, processes and architectures should incorporate considerations related to both privacy and security. This incorporation may benefit from the offering of appropriate training. In this way, this paper intends to discuss how to better offer training while considering new developments that involve both multimedia production and the “gamification” of training. The paper suggests the use in conjunction of two frameworks: the EduPMO Framework, useful for the management of large scale projects that may involve a consortium of organizations developing multimedia for the offering of training, and the Game Development Framework, useful for the identification of the main components of the serious game for training on privacy by design to be developed as part of the training offering.
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| 16. |
- Andler, Sten F., et al.
(författare)
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SMARTracIn : a concept for spoof resistant tracking of vessels and detection of adverse intentions
- 2009
-
Ingår i: Sensors, and Command, Control, Communications, and Intelligence (C3I) Technologies for Homeland Security and Homeland Defense VIII. - : SPIE - International Society for Optical Engineering. - 9780819475718 ; , s. 73050G-1-73050G-9
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Konferensbidrag (refereegranskat)abstract
- The aim of maritime surveillance systems is to detect threats earlyenough to take appropriate actions. We present the results ofa study on maritime domain awareness performed during the fallof 2008. We analyze an identified capability gap of worldwidesurveillance in the maritime domain, and report from a userworkshop addressing the identified gap. We describe a SMARTracIn conceptsystem that integrates information from surveillance systems with background knowledgeon normal conditions to help users detect and visualize anomaliesin vessel traffic. Land-based systems that cover the coastal watersas well as airborne, space-borne and ships covering open seaare considered. Sensor data are combined with intelligence information fromship reporting systems and databases. We describe how information fusion,anomaly detection and semantic technology can be used to helpusers achieve more detailed maritime domain awareness. Human operators area vital part of this system and should be activecomponents in the fusion process. We focus on the problemof detecting anomalous behavior in ocean-going traffic, and a roomand door segmentation concept to achieve this. This requires theability to identify vessels that enter into areas covered bysensors as well as the use of information management systemsthat allow us to quickly find all relevant information.
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| 17. |
- Atif, Yacine, 1967-, et al.
(författare)
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Cyber-Threat Intelligence Architecture for Smart-Grid Critical Infrastructures Protection
- 2017
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Konferensbidrag (refereegranskat)abstract
- Critical infrastructures (CIs) are becoming increasingly sophisticated with embedded cyber-physical systems (CPSs) that provide managerial automation and autonomic controls. Yet these advances expose CI components to new cyber-threats, leading to a chain of dysfunctionalities with catastrophic socio-economical implications. We propose a comprehensive architectural model to support the development of incident management tools that provide situation-awareness and cyber-threats intelligence for CI protection, with a special focus on smart-grid CI. The goal is to unleash forensic data from CPS-based CIs to perform some predictive analytics. In doing so, we use some AI (Artificial Intelligence) paradigms for both data collection, threat detection, and cascade-effects prediction.
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| 18. |
- Blais, Curtis, et al.
(författare)
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An Architecture for Demonstrating the Interplay of Emerging SISO standards
- 2006
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Ingår i: Fall Simulation Interoperability Workshop (FallSIW). - 1930638450 - 9781622761425 ; , s. 441-451
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The Simulation Interoperability Standards Organization (SISO) focuses on facilitating simulation interoperability across government and non-government applications worldwide. A number of standards are emerging that will individually have great impact on the development and operation of simulation systems, as well as interoperation across simulation systems and command and control systems. More importantly, when these standards are applied together, they represent a set of capabilities and technologies which can revolutionize the simulation industry, radically improving the way we develop and deliver interoperable systems.Each of the following standards addresses specific needs that have been shortcomings in M&S interoperability in the past: (1) the Coalition Battle Management Language (C-BML) provides a way to represent the coalition battle management doctrine within a Command and Control environment to enable unambiguous expression of plans and orders for live, constructive, and robotic forces; (2) the Military Scenario Definition Language (MSDL) provides a common way to describe a scenario, including initialization information, that can be shared across multiple systems; (3) the Base Object Model (BOM) standard provides a way to identify piece parts of a simulation or model that can be used as building blocks for composing larger model sets; (4) the Simulation Reference Markup Language (SRML) provides a platform-independent way to represent behavior models which can be rendered quickly and easily (at runtime) by a simulation; and (5) the Distributed Interactive Simulation Extensible Markup Language (DIS-XML) initiative provides a way to represent DIS Protocol Data Units using XML to enhance interchange of dynamic entity state and entity interactions across diverse systems.This paper gives a brief overview of these key standardization efforts, and explores how each standard can interplay with other standards. The paper lays out an abstract architecture for demonstration of the composition of prototype versions of these products to show the community how they will be employed in the future and what benefits will accrue. The paper proposes a plan of action to implement the architecture for demonstration and discussion at the Spring 2007 Simulation Interoperability Workshop.
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| 19. |
- Carling, Tobias, et al.
(författare)
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Familial hypercalcemia and hypercalciuria caused by a novel mutation in the cytoplasmic tail of the calcium receptor
- 2000
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - 0021-972X .- 1945-7197. ; 85:5, s. 2042-7
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Tidskriftsartikel (refereegranskat)abstract
- Familial hyperparathyroidism (HPT), characterized by hypercalcemia and hypercalciuria, and familial benign hypocalciuric hypercalcemia (FHH) are the most common causes of hereditary hypercalcemia. The calcium-sensing receptor (CaR) regulates PTH secretion and renal calcium excretion. Heterozygous inactivating mutations of the gene cause FHH, whereas CaR gene mutations have not been demonstrated in HPT. In a kindred with 20 affected individuals, the hypercalcemic disorder segregated with inappropriately higher serum PTH and magnesium levels and urinary calcium levels than in unaffected members. Subtotal parathyroidectomy revealed parathyroid gland hyperplasia/adenoma and corrected the biochemical signs of the disorder in seven of nine individuals. Linkage analysis mapped the condition to markers flanking the CaR gene on chromosome 3q. Sequence analysis revealed a mutation changing phenylalanine to leucine at codon 881 of the CaR gene, representing the first identified point mutation located within the cytoplasmic tail of the CaR. A construct of the mutant receptor (F881L) was expressed in human embryonic kidney cells (HEK 293), and demonstrated a right-shifted dose-response relationship between the extracellular and intracellular calcium concentrations. The hypercalcemic disorder of the present family is caused by an inactivating point mutation in the cytoplasmic tail of the CaR and displays clinical characteristics atypical of FHH and primary HPT.
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| 20. |
- Devarakonda, Sravani, et al.
(författare)
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Low-grade intestinal inflammation two decades after pelvic radiotherapy.
- 2023
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Ingår i: EBioMedicine. - 2352-3964. ; 94
-
Tidskriftsartikel (refereegranskat)abstract
- Radiotherapy is effective in the treatment of cancer but also causes damage to non-cancerous tissue. Pelvic radiotherapy may produce chronic and debilitating bowel symptoms, yet the underlying pathophysiology is still undefined. Most notably, although pelvic radiotherapy causes an acute intestinal inflammation there is no consensus on whether the late-phase pathophysiology contains an inflammatory component or not. To address this knowledge gap, we examined the potential presence of a chronic inflammation in mucosal biopsies from irradiated pelvic cancer survivors.We biopsied 24 cancer survivors two to 20 years after pelvic radiotherapy, and four non-irradiated controls. Using tandem mass tag (TMT) mass spectrometry and mRNA sequencing (mRNA-seq), we charted proteomic and transcriptomic profiles of the mucosal tissue previously exposed to a high or a low/no dose of radiation. Changes in the immune cell populations were determined with flow cytometry. The integrity of the protective mucus layers were determined by permeability analysis and 16S rRNA bacterial detection.942 proteins were differentially expressed in mucosa previously exposed to a high radiation dose compared to a low radiation dose. The data suggested a chronic low-grade inflammation with neutrophil activity, which was confirmed by mRNA-seq and flow cytometry and further supported by findings of a weakened mucus barrier with bacterial infiltration.Our results challenge the idea that pelvic radiotherapy causes an acute intestinal inflammation that either heals or turns fibrotic without progression to chronic inflammation. This provides a rationale for exploring novel strategies to mitigate chronic bowel symptoms in pelvic cancer survivors.This study was supported by the King Gustav V Jubilee Clinic Cancer Foundation (CB), The Adlerbertska Research Foundation (CB), The Swedish Cancer Society (GS), The Swedish State under the ALF agreement (GS and CB), Mary von Sydow's foundation (MA and VP).
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| 21. |
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| 22. |
- Gad, Helge, et al.
(författare)
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MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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| 23. |
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| 24. |
- Gustavsson, Per M., 1965-, et al.
(författare)
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Expanding the management language smorgasbord towards standardization of Coalition - Crisis Management Language (C-CML)
- 2006
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Ingår i: Spring SIW 2006. - : SISO - Simulation Interoperability Standards Organization. - 9781615671731 ; , s. 1-12, s. 1-14
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Just as the present revolution in military affairs has formed the thoughts of joint and coalition forces between national and international militaries, a future revolution is also facing civilian authorities and agencies. Exchanging commander intent and collecting, fusing, and sharing a common operational picture between commanders and grassroots from various civilian authorities/agencies is not easily done. Laws prohibit information exchange, systems are not intended to share information and there is no or little formal training between authorities/agencies.For both simulated and real world operations, an unambiguous language to describe a commander's intent in Crisis Management is needed. The resemblance with the ongoing standardization of the Coalition Battle Management Language (C-BML) is striking. In this paper the idea to form a CML aligned with C-BML is presented. The ongoing standardization effort of a Societal Security1 standard within the frame of ISO/TC-223 and the Emergency Data Exchange Language (EDXL) is introduced. The authors identifies some potential research topics and propose that the work in defining a Crisis Management Language, which is aligned with and benefits from the accomplishments of the ongoing C-BML standardization, is performed under the embracement of SISO.
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| 25. |
- Gustavsson, Per M., 1965-, et al.
(författare)
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Formalizing operations intent and effects for network-centric applications
- 2009
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Ingår i: Proceedings of the 42nd Annual Hawaii International Conference on System Sciences, HICSS. - : IEEE Computer Society. - 9780769534503
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Konferensbidrag (refereegranskat)abstract
- A Network-Centric approach enables systems to be interconnected in a dynamic and flexible architecture to support multi-lateral, civilian and military missions. Constantly changing environments require commanders to plan for more flexible missions that allow organizations from various nations and agencies to join or separate from the teams performing the missions, depending on the situation. The uncertainty inherent in an actual mission, and the variety of potential organizations that support the mission after it is underway, makes Command Intent (CI) a critical concept for the mission team. Both humans and computerized decision support services need to have the ability to communicate and interpret a shared CI. This paper presents the Operations Intent and Effects Model (OIEM) - a model that relates CI to Effects, and supports both traditional military planning and Effects Based Operation. In the provided example the suggested Command and Control Language is used to express Operations Intent and Effects. © 2009 IEEE.
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| 26. |
- Gustavsson, Per M., et al.
(författare)
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Learning Priorities and the Role of Computer-Based Training and Simulation on Military Supply Chain Logistics
- 2013
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Konferensbidrag (refereegranskat)abstract
- Military training involves activities that range from combat operations to strategic decisions on how to locate and transport personal and supplies, such as food, ammunition, fuel and medical equipment. Despite of the fact that most military training is difficult to acquire from real situations, the skills required for learning from combat training technology are different from those required for training on military logistics. This research work aims to analyse learning priorities and the role of Computer-Based Training and Simulation (CBTS) on Military Supply Chain Logistics. Military logistics is a complex task that requires expertise for decisions on such factors as: (i) the mission to accomplish; (ii) the place to locate troops and all military facilities at the Area of Operations (AOO); the (iii) combat readiness level that will be expected to equip all the military operations; and the (iv) use of transportation resources and paths to follow in the AOO. In this work, each one of these factors is represented by a number of variables that must be considered as whole to outline the best decisions on supply chain logistics for each military operation. To identify training priorities for considering the implications of all variables that respond for these four factors, this work carried out a qualitative research with in depth interviews with military personal with expertise on making decisions about military logistics. Results from this research shows the skills that are most important to follow for developing expertise on military supply chain logistics and the technology that should best be applied to enhance the training experience. Conclusions from this work shows that training on military logistics involve decisions that are mostly unique, though the current computer-based technology has an important role for training and simulating field situations, thus enhancing the required expertise for making decisions on real military supply chain operations.
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| 27. |
- Gustavsson, Per M., 1965-, et al.
(författare)
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Machine Interpretable Representation of Commander's Intent
- 2008
-
Ingår i: Proceedings of the 13th International Command and Control Research and Technology Symposium (13th ICCRTS).
-
Konferensbidrag (refereegranskat)abstract
- The Network-Centric approach envisioned in the Global Information Grid enables the interconnection of systems in a dynamic and flexible architecture to support multi-lateral, civilian and military missions. Constantly changing environments require commanders to plan for missions that allow organizations from various nations and agencies to join or separate from the teams performing the missions, depending on the situation, as missions unfold. The uncertainty within an actual mission, and the variety of potential organizations that support the mission after it is underway, makes Command Intent (CI) a critical concept for the mission team. With new and innovative information technologies, CI can now be made available to the team of organizations in a coalition environment. Using a flexible and linguistically based approach for representing CI allows Intent to be interpreted and processed by all participants – both humans and machines. CI representations need to be able to express mission team’s purpose, the anticipated End-State of the mission and desired key tasks. In this work, the expression of CI is developed to enable the structure and dynamics of collaboration support.
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| 28. |
- Gustavsson, Per M.
(författare)
-
Modelling, Formalising, and Implementing Intent in Command and Control Systems
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Intent is a fundamental element in military Command and Control (C2) systems. The ability for a commander to communicate Intent is vital to lead subordinates so that the overall mission is completed in the best possible way. However, the expressiveness of Intent is limited in current C2 systems. The current data exchange models are not capable of representing Intent in a machine interpretable format.An essential problem to overcome before Intent can be inserted into C2 systems, is to define it to a sufficient level of detail, since different definitions of Intent exist. If this problem can be overcome, the next problem is to represent Intent in such a way that it fits with existing C2 formalisms. The final problem is to what degree the proposed representation of Intent can be inserted into existing and future C2 systems.This thesis presents how to model and formalise Intent to such a degree that it can be communicated and automatically processed in military C2 systems. The contributions are: a literature review over Intent in C2; a model that captures and relates Intent to key information elements and processes in C2; a formalisation of Intent into a computational tractable representation covering the information elements defined in the developed model; an implementation of the model and formalism into an architectural design for Intent in C2 systems; and a series of demonstrations of the implementation in current C2 systems and simulators that show that the suggested model, formalism and implementation is suitable to represent Intent to such degree that Intent can be represented, exchanged, visualised and executed within current and forthcoming C2 systems.
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| 29. |
- Gustavsson, Per M., 1965-, et al.
(författare)
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Operations Intent and Effects Model
- 2011
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Ingår i: The Journal of Defence Modeling and Simulation. - : Sage Publications. - 1548-5129 .- 1557-380X. ; 8:1, s. 37-59
-
Tidskriftsartikel (refereegranskat)abstract
- Military missions in the 21st century are characterized by combinations of traditional symmetric conventional warfare, irregular warfare, and operations other than war. The inherent uncertainty in an actual mission and the variety of potential organizations (e.g. multi-agency, non-governmental, private volunteer, international, international corporations) from several countries that support the mission makes collaboration and co-ordination a key capability for command and control. The ability to communicate and automatically process intent and effects is vital in order for a commander to cooperate with other organizations and agencies and lead subordinates in such a way that the overall mission is completed in the best possible way, including exploitation of fleeting opportunities, i.e. enable for self-synchronization amongst teams and allow for subordinate initiatives. However, intent and effects are often absent in the current and forthcoming digitalized information models, and if intent and effects are present it is likely to be found that the representations are made as free-text fields based on natural language. However, such messages are very difficult to disambiguate, particularly for automated machine systems. The overall objective for the Operations Intent and Effects Model is to support operational and simulated systems by a conceptual intent and effects model and a formalism that is human and machine interpretable.
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| 30. |
- Gustavsson, Per M., et al.
(författare)
-
Service Oriented Simulations Concept
- 2005
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Ingår i: Proceedings of the 10th Simulation conference and exhibition. ; , s. 533-538
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- In the effort to provide simulation support to the future Network Based Defence (NBD) that are currently being applied by the Swedish Armed Forces (SwAF), and the similair work within US and NATO, the authors opinion is that simulation should be treated as any other services, existing in the operational systems. Meaning that architecture should be conformant between the operational and simulated systems, for a start use the same infrastructure. The choice so far for simulation is the High Level Architecture (HLA). During the author’s participation in ongoing work supporting NBD, questions have gradually been raised if HLA is the simulation path to walk. In the Core Enterprise Services (CES) and Swedish Armed Force Enterprise Architecture (FMA) Services IT-Kernel, core services are specified and HLA do address a lot of non-simulation specific services giving unwanted redundancy. However, the services already defined may with some enhancements deliver the same services addressed within FMA Services ITKernel. The Next Generation HLA could be more than just a simulation standard if it utilizes the FMA ideas. In this paper the authors present the ongoing work, as it stands today, with Service Oriented Simulations, that is an outlook for simulation using the architectural structuring, services, components and infrastructures concepts evolving in FMA and Global Information Grid (GIG). The focus of the work is to enable interoperable simulation support for the whole system lifecycle – Acquisition, Development, Training, Planning, In-the-Field decision support, System removal – within NBD, entailing that the architecture for simulation is uniform regardless of its application and giving end-users the capability to focus on what to simulate instead of how to simulate.
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| 31. |
- Gustavsson, Per M., 1965-, et al.
(författare)
-
Towards Service Oriented Simulations
- 2004
-
Ingår i: Fall Simulation Interoperability Workshop 2004. ; , s. 219-229
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- In the effort to provide simulation support to the future Network Based Defence (NBD)1 that are currently being applied by the Swedish Armed Forces (SwAF), the authors opinion is that simulation should be treated as any other services and use the same architectural requirements addressed in the SwAF Enterprise Architecture (FMA)2 and in subsidiary documents.The choice so far for simulation is the High Level Architecture (HLA). During the author’s participation in ongoing work supporting NBD, questions have gradually been raised if HLA is the simulation path to walk. In the Core Enterprise Services (CES) and FMA Services IT-Kernel, core services are specified and HLA do address a lot of non-simulation specific services giving unwanted redundancy. However, the services already defined may with some enhancements deliver the same services addressed within CES and FMA Services IT-Kernel. Furthermore, HLA also comes with the Federation Development and Execution Process (FEDEP) that introduce process methodology to build HLA federations. Basically FEDEP is a software development process for distributed systems. The Next Generation HLA could be more than just a simulation standard if it utilizes the FMA ideas and avoids the green HLA elephant3.In this paper the authors present the ongoing work, as it stands today, with Service Oriented Simulations, that is an outlook for simulation using the architectural structuring, services, components and infrastructures concepts evolving in FMA and with the Global Information Grid (GIG) Enterprise Services (GES) in mind. The focus is to identify simulation services that encapsulate the core features of simulation. Thereby reducing redundancy in methodology and service as well as enabling interoperable simulation support for the whole system lifecycle – Acquisition, Development, Training, Planning, In-the-Field decision support, System removal – within NBD, entailing that the architecture for simulation is uniform regardless of its application and giving end-users the capability to focus on what to simulate instead of how to simulate.
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| 32. |
- Kalkner, Karl Mikael, et al.
(författare)
-
Octreotide scintigraphy and Chromogranin A do not predict clinical response in patients with octreotide acetate-treated hormone-refractory prostate cancer
- 2006
-
Ingår i: Prostate Cancer and Prostatic Diseases. - : Springer Science and Business Media LLC. - 1476-5608 .- 1365-7852. ; 9:1, s. 92-98
-
Tidskriftsartikel (refereegranskat)abstract
- In this pilot study, the predictive value of Octreotide scintigraphy (Octreoscan) and/or Chromogranin-A (CgA) was investigated in patients with hormone-refractory prostate cancer treated with Octreotide acetate. In total, 20 patients with progressive disease and bone metastases entered the trial. At baseline Octreoscan, CgA, PSA, alkaline phosphates (ALP) and two self-administered questionnaires (EORTC QLQ C-30 (v3) and brief pain index) were performed and a diary of the pharmaceutical was started. The treatment consisted of Octreotide (Sandostatin LAR) acetate 30 mg intramuscular injection every month. The blood samples and questionnaires were repeated every month until 3 months. Clinical responder was defined as a patient with increased global health score more than 10 units and stable or decreased pain score without an increase in analgesic. In all, 17 patients were treated per protocol, and four were assessed as clinical responders. Six patients developed a reduction in ALP (median -26%, range -5 to -78%). All patients increased in PSA. At baseline, three patients had a negative Octreoscan and the patients with positive lesions, demonstrated uptake of low intensity. At baseline the CgA was elevated above the normal range in 15 of the patients, and during treatment five patients decreased their CgA to the normal range. Neither baseline Octreoscan nor CgA could identify the clinical reponders. A minority of patients improves their health-related quality of life. The decrease and normalization of CgA levels in five patients during therapy indicates therapeutic activity but Octreoscan and CgA could not identify clinical responders.
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| 33. |
- Lagervik, Charlie, et al.
(författare)
-
A System Theoretical Approach to Situation Awareness : A Holistic View of Purposeful Elements
- 2006
-
Ingår i: 9th International Conference on Information Fusion. - : IEEE. - 9781424409532 ; , s. 1-7
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- This paper executes a comparison of the theories by Ackoff and Bedny & Meister for situation awareness (SA). The comparison gives a conceptual design for the common part of SA, a design that involves concepts like conscious and unconscious processes, gnostic activity, active and passive memory and dynamic processes. The design captures the ideas presented by Ackoff for adoption and learning, and is intended to work with social systems as described by Ackoff. The aim of the paper is to fill the need of conceptual general designs for SA systems. As result a definition of SA is presented, the result of the comparison of theories is presented, discussed and summarized in a conceptual design
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| 34. |
- Lagervik, Charlie, et al.
(författare)
-
A System Theoretical Approach to Situation Awareness and Architecture
- 2006
-
Ingår i: International Command and Control Research and Technical symposium. ; , s. 16 s.-
-
Konferensbidrag (refereegranskat)abstract
- This paper executes a comparison of the theories by Ackoff and Bedny & Meister for situation awareness (SA). The comparison gives a conceptual design for the common part of SA. An example of an architecture that uses the concepts is presented. The conceptual design involves concepts like conscious and unconscious processes, gnostic activity, active and passive memory and dynamic processes. The design captures the ideas presented by Ackoff for adoption and learning, and is intended to work with social systems as described by Ackoff. The aim of the paper is to fill the hole of conceptual general designs for SA systems. This paper presents a conceptual definition of SA and the comparison result between the two theories. The conceptual design is then used in the development of an Agent Architecture for Multi-Hypothesis Intention Simulation. Suggested future research is presented.
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| 35. |
- Lund, Line Naomi, et al.
(författare)
-
Novel peptide ligand with high binding capacity for antibody purification
- 2012
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Ingår i: Journal of Chromatography A. - : Elsevier BV. - 0021-9673. ; 1225, s. 158-167
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Tidskriftsartikel (refereegranskat)abstract
- Small synthetic ligands for protein purification have become increasingly interesting with the growing need for cheap chromatographic materials for protein purification and especially for the purification of monoclonal antibodies (mAbs). Today, Protein A-based chromatographic resins are the most commonly used capture step in mAb down stream processing; however, the use of Protein A chromatography is less attractive due to toxic ligand leakage as well as high cost. Whether used as an alternative to the Protein A chromatographic media or as a subsequent polishing step, small synthetic peptide ligands have an advantage over biological ligands; they are cheaper to produce, ligand leakage by enzymatic degradation is either eliminated or significantly reduced, and they can in general better withstand cleaning in place (CIP) conditions such as 0.1 M NaOH. Here, we present a novel synthetic peptide ligand for purification of human IgG. Immobilized on WorkBeads, an agarose-based base matrix from Bio-Works, the ligand has a dynamic binding capacity of up to 48 mg/mL and purifies IgG from harvest cell culture fluid with purities and recovery of >93%. The binding affinity is similar to 10(5) M-1 and the interaction is favorable and entropy-driven with an enthalpy penalty. Our results show that the binding of the Fc fragment of IgG is mediated by hydrophobic interactions and that elution at low pH is most likely due to electrostatic repulsion. Furthermore, we have separated aggregated IgG from non-aggregated IgG, indicating that the ligand could be used both as a primary purification step of IgG as well as a subsequent polishing step. (C) 2012 Elsevier B.V. All rights reserved.
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| 36. |
- Mellin, Jonas, et al.
(författare)
-
Using Imprecise Computation for Virtual and Constructive Simulations
- 2014
-
Ingår i: Proceedings of the 2014 Winter Simulation Conference. - : IEEE Press. - 9781479974863 ; , s. 4043-4044
-
Konferensbidrag (refereegranskat)abstract
- In this work, we raise three critical questions that must be investigated to ameliorate composability ofvirtual simulation models and to enable adoption of systematic and stringent real-time techniques toenable more scalable simulation models for virtual and constructive simulation. The real-time techniquesin question enable us to separate between policies and mechanisms and, thus, the simulation engine candecide dynamically how to run the simulation given the existing resources (e.g., processor) and the goalsof the simulation (e.g., sufficient fidelity in terms of timing and accuracy). The three critical questionsare: (i) how to design efficient and effective algorithms for making dynamic simulation model designdecisions during simulation; (ii) how to map simulation entities (e.g., agents) into (real-time) tasks; and(iii) how to enable a divide and conquer approach to validating simulation models.
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| 37. |
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| 38. |
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| 39. |
- Niklasson, Lars, et al.
(författare)
-
Extending the scope of Situation Analysis
- 2008
-
Ingår i: Proceedings of the 11th International Conference on Information Fusion (FUSION 2008)<em></em>, Cologne, Germany, June 30–July 3, 2008. - : IEEE Press. - 9783000248832 ; , s. 454-461
-
Konferensbidrag (refereegranskat)abstract
- The use of technology to assist human decision making has been around for quite some time now. In the literature, models of both technological and human aspects of this support can be identified. However, we argue that there is a need for a unified model which synthesizes and extends existing models. In this paper, we give two perspectives on situation analysis: a technological perspective and a human perspective. These two perspectives are merged into a unified situation analysis model for semi-automatic, automatic and manual decision support (SAM)2. The unified model can be applied to decision support systems with any degree of automation. Moreover, an extension of the proposed model is developed which can be used for discussing important concepts such as common operational picture and common situation awareness.
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| 40. |
- Pietra, Stefano, 1980-, et al.
(författare)
-
Arabidopsis SABRE and CLASP interact to stabilize cell division plane orientation and planar polarity
- 2013
-
Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 4, s. 2779-
-
Tidskriftsartikel (refereegranskat)abstract
- The orientation of cell division and the coordination of cell polarity within the plane of the tissue layer (planar polarity) contribute to shape diverse multicellular organisms. The root of Arabidopsis thaliana displays regularly oriented cell divisions, cell elongation and planar polarity providing a plant model system to study these processes. Here we report that the SABRE protein, which shares similarity with proteins of unknown function throughout eukaryotes, has important roles in orienting cell division and planar polarity. SABRE localizes at the plasma membrane, endomembranes, mitotic spindle and cell plate. SABRE stabilizes the orientation of CLASP-labelled preprophase band microtubules predicting the cell division plane, and of cortical microtubules driving cell elongation. During planar polarity establishment, sabre is epistatic to clasp at directing polar membrane domains of Rho-of-plant GTPases. Our findings mechanistically link SABRE to CLASP-dependent microtubule organization, shedding new light on the function of SABRE-related proteins in eukaryotes.
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| 41. |
- Pozzer, Cesar, et al.
(författare)
-
Imprecise Computation as an Enabler for Complex and Time Critical HLA Simulation Networks
- 2014
-
Ingår i: Proceedings of Simulation Interoperability Workshop. - 9781634393898 ; , s. 171-179
-
Konferensbidrag (refereegranskat)abstract
- A trend over the past years is that simulation systems for training are being connected in simulation networks, allowing the interaction of teams spread in distributed sites. By combining interconnected simulation systems the simulation complexity increases and may affect time-critical simulation tasks in a negative way. As a consequence, the training simulation objectives may not be met. The same problem may occur when performing, for example, mission rehearsal on site, since available computation resources are usually very limited in this scenario, or for a joint fires scenario, where the large and complex functional chain (including intelligence, C2, forward observer, pilots, etc.) may overload existing resources. In this work, the technique of imprecise computation in real-time systems (ICRS) to preserve time-critical simulation tasks is presented. The ICRS technique allows time-critical tasks to produce quicker solutions for approximate results and saves computational resources. This paper discusses the main advantages of theICRS technique by a review of the commonly used optimization concepts built upon imprecise computation field. Thepaper ends with presenting a work-in-progress: an architectural solution for aligning ICRS with the High Level Architecture (HLA), standardized as the IEEE 1516-series.
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| 42. |
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| 43. |
- Rasmusson, J.R., et al.
(författare)
-
Bistatic VHF and UHF SAR for urban environments
- 2007
-
Ingår i: Proceedings of SPIE -- Volume 6547, Radar Sensor Technology XI, James L. Kurtz, Robert J. Tan, Editors, 654705, May 2, 2007. ; 6547
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 44. |
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| 45. |
- Riveiro, Maria, 1978-, et al.
(författare)
-
Enhanced Training through Interactive Visualization of Training Objectives and Models
- 2016
-
Ingår i: Proceedings of the STO-MP-MSG-143, Ready for the Predictable, Prepared for the Unexpected. - : NATO Science & Technology Organization (STO). - 9789283720607
-
Konferensbidrag (refereegranskat)abstract
- Military forces operate in complex and dynamic environments [1] where bad decisions might have fatal consequences. A key ability of the commander, team and individual warfighter is to quickly adapt to novel situations. Live, Virtual and Constructive training environments all provide elements of best practices for this type of training. However, many of the virtual training are designed without thorough consideration of the effectiveness and efficiency of embedded instructional strategies [2], and without considering the cognitive capabilities and limitations of trainees. As highlighted recently by Stacy and Freeman [3], large military training exercises require a significant commitment of resources, and to net a return on that investment, training scenarios for these events should systematically address well-specified training objectives, even if they often, do not.In order to overcome these shortcomings with both Live and Virtual training systems and following our previous work [4,5,6], this paper presents a design solution for a proof-of-concept prototype that visualizes and manages training objectives and performance measures, at individual and collective levels. To illustrate its functionality we use real-world data from Live training exercises. Finally, this paper discusses how to learn from previous training experiences using data mining methods in order to build training models to provide instructional personalized feedback to trainees.
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| 46. |
- Rubio, Carlos A., et al.
(författare)
-
Assessing the Size of Polyp Phantoms in Tandem Colonoscopies
- 2009
-
Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 29:5, s. 1539-1545
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The size of colorectal neoplastic polyps is important for their clinical management. Materials and Methods: The size of 12 polyp phantoms was assessed in tandem colonoscopies carried out by 7 endoscopists differing in years of clinical endoscopical experience. The endoscopists measured, with (n=5) or without (n=2) the aid of open forceps, the largest diameter of 12 polyp phantoms. Measurements in two independent trials were compared with the gold standard-size assessed at The Department Of Production Engineering, The Royal Institute of Technology. Results: In tandem trials, 99.4% (167/168) of the measurements underscored the gold standard size. In the 1st trial, the size in all 84 measurements was underestimated by -40% (range -34% to -45%) and in the 2nd trial the size in 83 of the 84 measurements was underestimated by -34% (range -24% to -42%). Neither the age of the participant, nor the years of experience with clinical endoscopy improved the results obtained. The participants significantly underestimated larger devices (>= 20 mm) whereas the smallest "polyps" were also underestimated, but with a lower degree of inaccuracy. The absolute difference between the golden standard size and the mean of all measurements performed on each polyp in 167 out of 168 measurements followed a regular downward trend. The volume of the devices was one of the confounding factors in size assessment. When compared to the gold standard size, the larger the "polyp" size, the higher the degree of underestimation. This may be crucial considering that the risk for colorectal adenomas to shelter an invasive growth is 46%, for adenomas measuring >= 2 cm, a limit accepted as a guideline worldwide for the management of patients with large colorectal polyps. Conclusion: Considering the clinical implications of the results obtained, the possibility of developing a method that would allow the assessment of the true size of polyps in clinical colonoscopy, is being explored.
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| 47. |
- Sivertsson, Åsa, et al.
(författare)
-
Enhanced Validation of Antibodies Enables the Discovery of Missing Proteins
- 2020
-
Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 19:12, s. 4766-4781
-
Tidskriftsartikel (refereegranskat)abstract
- The localization of proteins at a tissue- or cell-type-specific level is tightly linked to the protein function. To better understand each protein's role in cellular systems, spatial information constitutes an important complement to quantitative data. The standard methods for determining the spatial distribution of proteins in single cells of complex tissue samples make use of antibodies. For a stringent analysis of the human proteome, we used orthogonal methods and independent antibodies to validate 5981 antibodies that show the expression of 3775 human proteins across all major human tissues. This enhanced validation uncovered 56 proteins corresponding to the group of "missing proteins" and 171 proteins of unknown function. The presented strategy will facilitate further discussions around criteria for evidence of protein existence based on immunohistochemistry and serves as a useful guide to identify candidate proteins for integrative studies with quantitative proteomics methods.
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| 48. |
- Tiberg, Jesper, et al.
(författare)
-
Towards Hypothesis Evaluation in Command and Control Systems
- 2006
-
Ingår i: Proceedings of SAIS 2006. - Umeå : Swedish Artificial Intelligence Society - SAIS. ; , s. 97-102
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- This work focus on situation prediction in data fusion systems. A hypothesis evaluation algorithm based on artificial neural networks is introduced. It is evaluated and compared to an algorithm based on Bayesian networks which is commonly used. It is also compared to a simple "dummy" algorithm. For the tests, a computer based model of the environment, including protected objects and enemy objects, is implemented. The model handles the navigation of the enemy objects and situational data is extracted from the environment and provided for the hypothesis evaluation algorithms. It was the belief of the author that ANNs would be suitable for hypothesis evaluation if a suitable data representation of the environment were used. The representation requirements include pre processing of the situational data to eliminate the need for variable input size to the algorithm. This because ANNs poorly handles this; the whole network have to be retrained each time the amount of input data changes. The results show that ANNs performed best of the three and hence seems to be suitable for hypothesis evaluation.
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| 49. |
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| 50. |
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