Logic-Based Conflict Analysis and Resolution

<p>The aim of this thesis is to explore the extent to which formal logic can be applied to the topic of conflict analysis and conflict resolution. It is motivated by the idea that conflicts can be understood as inconsistent sets of goals, beliefs, norms, emotions, or the like. To achieve this aim, two formal frameworks are presented. Conflict Modelling Logic (CML) is a logical system, based on branching-time temporal logic, which can be used to describe and interpret conflicts. Conflict Resolution Logic (CRL) is a set of five algorithms, inspired by the AGM model of belief revision, which can be used to generate possible solutions to conflicts. Furthermore, two numerical measures for the 'potential conflict power' of propositional formulae and the 'degree of inconsisteny' of sets of propositional formulae are introduced. The two measures allow one to assess the role of particular elements within a conflict and the depth of a conflict. The formal framework is illustrated with the example conflict of the Second Congo War.</p>

Logic-Based Conflict Analysis and Resolution

<p>The aim of this thesis is to explore the extent to which formal logic can be applied to the topic of conflict analysis and conflict resolution. It is motivated by the idea that conflicts can be understood as inconsistent sets of goals, beliefs, norms, emotions, or the like. To achieve this aim, two formal frameworks are presented. Conflict Modelling Logic (CML) is a logical system, based on branching-time temporal logic, which can be used to describe and interpret conflicts. Conflict Resolution Logic (CRL) is a set of five algorithms, inspired by the AGM model of belief revision, which can be used to generate possible solutions to conflicts. Furthermore, two numerical measures for the 'potential conflict power' of propositional formulae and the 'degree of inconsisteny' of sets of propositional formulae are introduced. The two measures allow one to assess the role of particular elements within a conflict and the depth of a conflict. The formal framework is illustrated with the example conflict of the Second Congo War.</p>

An Orally Available Cathepsin L Inhibitor Protects Lungs Against SARS-CoV-2-Induced Diffuse Alveolar Damage in African Green Monkeys

The COVID-19 pandemic resulted from global infection by the SARS-CoV-2 coronavirus and rapidly emerged as an urgent health issue requiring effective treatments. To initiate infection, the Spike protein of SARS-CoV-2 requires proteolytic processing mediated by host proteases. Among the host proteases proposed to carry out this activation is the cysteine protease cathepsin L. Inhibiting cathepsin L has been proposed as a therapeutic strategy for treating COVID-19. SLV213 (K777) is an orally administered small molecule protease inhibitor that exhibits in vitro activity against a range of viruses, including SARS-CoV-2. To confirm efficacy in vivo, K777 was evaluated in an African green monkey (AGM) model of COVID-19. A pilot experiment was designed to test K777 in a prophylactic setting, animals were pre-treated with 100mg/kg K777 (N=4) or vehicle (N=2) before inoculation with SARS-CoV-2. Initial data demonstrated that K777 treatment reduced pulmonary pathology compared to vehicle-treated animals. A second study was designed to test activity in a therapeutic setting, with K777 treatment (33 mg/kg or 100 mg/kg) initiated 8 hours after exposure to the virus. In both experiments, animals received K777 daily via oral gavage for 7 days. Vehicle-treated animals exhibited higher lung weights, pleuritis, and diffuse alveolar damage. In contrast, lung pathology was reduced in K777-treated monkeys, and histopathological analyses confirmed the lack of diffuse alveolar damage. Antiviral effects were further demonstrated by quantitative reductions in viral load of samples collected from upper and lower airways. These preclinical data support the potential for early SLV213 treatment in COVID-19 patients to prevent severe lung pathology and disease progression.

Credibility-limited Base Revision: New Classes and Their Characterizations

In this paper we study a kind of operator —known as credibility-limited base revisions— which addresses two of the main issues that have been pointed out to the AGM model of belief change. Indeed, on the one hand, these operators are defined on belief bases (rather than belief sets) and, on the other hand, they are constructed with the underlying idea that not all new information is accepted. We propose twenty different classes of credibility-limited base revision operators and obtain axiomatic characterizations for each of them. Additionally we thoroughly investigate the interrelations (in the sense of inclusion) among all those classes. More precisely, we analyse whether each one of those classes is or is not (strictly) contained in each of the remaining ones.

Intranasal exposure of African green monkeys to SARS-CoV-2 results in acute phase pneumonia with shedding and lung injury still present in the early convalescence phase

We recently reported the development of the first African green monkey (AGM) model for COVID-19 based on a combined liquid intranasal (i.n.) and intratracheal (i.t.) exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we followed up on this work by assessing an i.n. particle only route of exposure using the LMA mucosal atomization device (MAD). Six AGMs were infected with SARS-CoV-2; three animals were euthanized near the peak stage of virus replication (day 5) and three animals were euthanized during the early convalescence period (day 34). All six AGMs supported robust SARS-CoV-2 replication and developed respiratory disease. Evidence of coagulation dysfunction as noted by a transient increases in aPTT and circulating levels of fibrinogen was observed in all AGMs. The level of SARS-CoV-2 replication and lung pathology was not quite as pronounced as previously reported with AGMs exposed by the combined i.n. and i.t. routes; however, SARS-CoV-2 RNA was detected in nasal swabs of some animals as late as day 15 and rectal swabs as late as day 28 after virus challenge. Of particular importance to this study, all three AGMs that were followed until the early convalescence stage of COVID-19 showed substantial lung pathology at necropsy as evidenced by multifocal chronic interstitial pneumonia and increased collagen deposition in alveolar walls despite the absence of detectable SARS-CoV-2 in any of the lungs of these animals. These findings are consistent with human COVID-19 further demonstrating that the AGM faithfully reproduces the human condition.

Intranasal Exposure of African Green Monkeys to SARS-CoV-2 Results in Acute Phase Pneumonia With Shedding and Lung Injury Still Present in the Early Convalescence Phase

We recently reported the development of the first African green monkey (AGM) model for COVID-19 based on a combined liquid intranasal (i.n.) and intratracheal (i.t.) exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we followed up on this work by assessing an i.n. particle only route of exposure using the LMA mucosal atomization device (MAD). Six AGMs were infected with SARS-CoV-2; three animals were euthanized near the peak stage of virus replication (day 5) and three animals were euthanized during the early convalescence period (day 34). All six AGMs supported robust SARS-CoV-2 replication and developed respiratory disease. Evidence of coagulation dysfunction as noted by a transient increases in aPTT and circulating levels of fibrinogen was observed in all AGMs. The level of SARS-CoV-2 replication and lung pathology was not quite as pronounced as previously reported with AGMs exposed by the combined i.n. and i.t. routes; however, SARS-CoV-2 RNA was detected in nasal swabs of some animals as late as day 15 and rectal swabs as late as day 28 after virus challenge. Of particular importance to this study, all three AGMs that were followed until the early convalescence stage of COVID-19 showed substantial lung pathology at necropsy as evidenced by multifocal chronic interstitial pneumonia and increased collagen deposition in alveolar walls despite the absence of detectable SARS-CoV-2 in any of the lungs of these animals. These findings are consistent with human COVID-19 further demonstrating that the AGM faithfully reproduces the human condition.

Effect of Delaying Treatment on Efficacy of Ciprofloxacin and Levofloxacin in the African Green Monkey Model of Pneumonic Plague

Background Ciprofloxacin and levofloxacin, 2 fluoroquinolone antimicrobials, are ≥90% effective for the treatment of inhalational plague when administered within 2–6 hours of fever onset in African green monkeys (AGM). Based on data in the AGM model, these antimicrobials were approved under the Food and Drug Administration’s Animal Efficacy Rule. However, that data did not address the issue of how long treatment with these antimicrobials would remain effective after fever onset. Methods The AGM model of pneumonic plague was used to explore the effect of delaying treatment with ciprofloxacin and levofloxacin on efficacy. In 2 studies, AGMs were challenged with inhaled lethal doses of Yersinia pestis. Treatment with ciprofloxacin and levofloxacin was initiated from 0 to up to 30 hours after fever onset. Results Challenged animals all developed fever within 78 hours and were treated with ciprofloxacin (n = 27) or levofloxacin (n = 29) at various predetermined time points postfever. When administered 10 hours after fever onset, 10 days of ciprofloxacin and levofloxacin treatment remained very effective (90 or 100%, respectively). The efficacy of both antimicrobials declined as treatment initiation was further delayed. Statistical analyses estimated the treatment delay times at which half of the AGMs were no longer expected to survive as 19.7 hours for ciprofloxacin and 26.5 hours for levofloxacin. Conclusions This study demonstrates that there is a narrow window following fever onset during which ciprofloxacin and levofloxacin are fully effective treatment options for pneumonic plague in AGMs. Since the timing of disease is similar in humans and AGMs, these AGM data are reasonably likely to predict response times for treatment in humans.

The Belief Model

Chapter 5 is an introduction to the AGM model of belief revision. It begins with an explanation of belief and how sets of sentences are used to model psychological states of an agent. The model’s norms are shown to flow directly from Jamesian ideas that inquiry targets truth and the avoidance of error. Suspended judgement and disbelief are discussed, and the model’s treatment of them is used to spell out its transition rules. Slowly and carefully the main technical idea in the model’s transition theory—known as ‘partial meet contraction’—is explained for the beginner. The model’s postulates are then listed, its revision theorem is explained, and its approach to conditional belief is spelled out. The chapter closes by describing a notionally possible agent, Bella, whose psychology matches the Belief Model.