An infrastructure mechanism for dynamic ontology-based knowledge infrastructures

Centre for Intelligent Systems and their ApplicationsBoth semantic web applications and individuals are in need of knowledge infrastructures that can be used in dynamic and distributed environments where autonomous entities create knowledge and build their own view of a domain. The prevailing view today is that the process of ontology evolution is difficult to monitor and control, so few efforts have been made to support such a controlled process formally involving several ontologies. The new paradigm we propose is to use an infrastructure mechanism that processes ontology change proposals from autonomous entities while maintaining user-defined consistency between the ontologies of these entities. This makes so called semantic autonomy possible. A core invention of our approach is to formalise consistency constraints as so called spheres of consistency that define 1) knowledge regions within which consistency is maintained and 2) a variable degree of proof-bounded consistency within these regions. Our infrastructure formalism defines a protocol and its computational semantics, as well as a model theory and proof theory for the reasoning layer of the mechanism. The conclusion of this thesis is that this new paradigm is possible and beneficial, assuming that the knowledge representation is kept simple, the ontology evolution operations are kept simple and one proposal is processed at a tim

Reasoning about multi-contextual ontology evolution

In this paper we develop a formalization and algorithms that can manage the evolution of several ontologies from different contexts, using automated reasoning. It is in general difficult to maintain consistency between several ontologies, but we focus on developing computationally efficient ways of achieving this. Our formalization uses both the notions of several local contexts and of a sequence of states. We believe such a system can become a component in for example a distributed knowledge management system or some other knowledge infrastructure that requires semantic autonomy, i.e. lack of centralized semantics, but presence of a type of semantic coherence. In this paper version we summarize our approach. Background and motivation 1 We envision that there will be a need for different kinds of systems that can support several ontologies, their individual evolution and maintain a type of coherence between them. For example, we would like to be able to build systems that will function as organizational knowledge infrastructures. The organizations using these will probably be decentralized and consist of separate divisions that have local autonomy in their knowledgecreating processes. Here we particularly mean semantic autonomy (see the partial definition in figure 1). Such an organization should act as a unified whole, because otherwise entities from outside (e.g. customers) interacting with the organization might be disappointed that it contradicts itself. Creating an organizational knowledge infrastructure is one application area (Zurawski, 2004), but there should exist other applications as well that also requires semantic autonomy. In both cases, this is modeled using several ontologies that can evolve, but where a kind of consistency is maintained between them

Hierarchically Federated Registration and Lookup within the perfSONAR Framework

A widely-distributed network monitoring system requires a scalable discovery mechanism. The “Lookup Service ” component of the perfSONAR framework is able to manage component registration, distill resource data into tractable units, and respond to queries regarding system and performance information. A model of organizing and distributing information is presented to support both dynamic environments where services frequently change as well where different administrative configuration requirements exist. These interactions are accomplished by forming “federated hierarchies ” to share information amongst the various logical overlays.

Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer

BACKGROUND Among patients with resectable early-stage non-small-cell lung cancer (NSCLC), a perioperative approach that includes both neoadjuvant and adjuvant immune checkpoint inhibition may provide benefit beyond either approach alone.METHODS We conducted a randomized, double-blind, phase 3 trial to evaluate perioperative pembrolizumab in patients with early-stage NSCLC. Participants with resectable stage II, IIIA, or IIIB (N2 stage) NSCLC were assigned in a 1:1 ratio to receive neoadjuvant pembrolizumab (200 mg) or placebo once every 3 weeks, each of which was given with cisplatin-based chemotherapy for 4 cycles, followed by surgery and adjuvant pembrolizumab (200 mg) or placebo once every 3 weeks for up to 13 cycles. The dual primary end points were event-free survival (the time from randomization to the first occurrence of local progression that precluded the planned surgery, unresectable tumor, progression or recurrence, or death) and overall survival. Secondary end points included major pathological response, pathological complete response, and safety.RESULTS A total of 397 participants were assigned to the pembrolizumab group, and 400 to the placebo group. At the prespecified first interim analysis, the median follow-up was 25.2 months. Event-free survival at 24 months was 62.4% in the pembrolizumab group and 40.6% in the placebo group (hazard ratio for progression, recurrence, or death, 0.58; 95% confidence interval [CI], 0.46 to 0.72; P<0.001). The estimated 24-month overall survival was 80.9% in the pembrolizumab group and 77.6% in the placebo group (P = 0.02, which did not meet the significance criterion). A major pathological response occurred in 30.2% of the participants in the pembrolizumab group and in 11.0% of those in the placebo group (difference, 19.2 percentage points; 95% CI, 13.9 to 24.7; P<0.0001; threshold, P = 0.0001), and a pathological complete response occurred in 18.1% and 4.0%, respectively (difference, 14.2 percentage points; 95% CI, 10.1 to 18.7; P<0.0001; threshold, P = 0.0001). Across all treatment phases, 44.9% of the participants in the pembrolizumab group and 37.3% of those in the placebo group had treatment-related adverse events of grade 3 or higher, including 1.0% and 0.8%, respectively, who had grade 5 events.CONCLUSIONS Among patients with resectable, early-stage NSCLC, neoadjuvant pembrolizumab plus chemotherapy followed by resection and adjuvant pembrolizumab significantly improved event-free survival, major pathological response, and pathological complete response as compared with neoadjuvant chemotherapy alone followed by surgery. Overall survival did not differ significantly between the groups in this analysis