Optimal solutions to matrix-valued Nehari problems and related limit theorems

In a 1990 paper Helton and Young showed that under certain conditions the optimal solution of the Nehari problem corresponding to a finite rank Hankel operator with scalar entries can be efficiently approximated by certain functions defined in terms of finite dimensional restrictions of the Hankel operator. In this paper it is shown that these approximants appear as optimal solutions to restricted Nehari problems. The latter problems can be solved using relaxed commutant lifting theory. This observation is used to extent the Helton and Young approximation result to a matrix-valued setting. As in the Helton and Young paper the rate of convergence depends on the choice of the initial space in the approximation scheme.Comment: 22 page

Joint Entity Recognition and Linking in Technical Domains Using Undirected Probabilistic Graphical Models

ter Horst H, Hartung M, Cimiano P. Joint Entity Recognition and Linking in Technical Domains Using Undirected Probabilistic Graphical Models. In: Gracia J, Bond F, McCrae JP, Buitelaar P, Chiarcos C, Hellmann S, eds. Language, Data, and Knowledge (Proceedings of the 1st International LDK Conference). Lecture Notes in Artificial Intelligence. Vol 10318. Springer; 2017: 166-180.The problems of recognizing mentions of entities in texts and linking them to unique knowledge base identifiers have received considerable attention in recent years. In this paper we present a probabilistic system based on undirected graphical models that jointly addresses both the entity recognition and the linking task. Our framework considers the span of mentions of entities as well as the corresponding knowledge base identifier as random variables and models the joint assignment using a factorized distribution. We show that our approach can be easily applied to different technical domains by merely exchanging the underlying ontology. On the task of recognizing and linking disease names, we show that our approach outperforms the state-of-the-art systems DNorm and TaggerOne, as well as two strong lexicon-based baselines. On the task of recognizing and linking chemical names, our system achieves comparable performance to the state-of-the-art

Visceral Leishmaniasis Relapse in Southern Sudan (1999–2007): A Retrospective Study of Risk Factors and Trends

Visceral leishmaniasis (kala-azar) caused by Leishmania donovani is spread from person to person by Phlebotomus sandflies. Major epidemics of visceral leishmaniasis have occurred in Southern Sudan during the 20th century. The worst of these killed 100,000 people in the western Upper Nile area of Southern Sudan from 1984–1994, a loss of one-third of the population. Médecins Sans Frontières has treated 40,000 kala-azar patients in Southern Sudan since the late 1980's. In this study we used routinely collected clinical data to investigate why some patients relapse after treatment. We found that patients with severely enlarged spleens (splenomegaly) are more likely to relapse. Patients treated for 17 days with a combination of two drugs (sodium stibogluconate and paromomycin) were more likely to relapse (but less likely to die) than patients treated for 30 days with a single drug (sodium stibogluconate). However, the transition from sodium stibogluconate to the sodium stibogluconate/paromomycin combination as standard treatment between 2001–2003 has not led to a significant increase in visceral leishmaniasis relapse

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Implications of COVID-19 Regulations for People With Visual and Intellectual Disabilities: Lessons to Learn From Visiting Restrictions

Background: Due to the COVID-19 pandemic, governments of many countries announced regulations to prevent the virus from spreading. For people with a disability living in a sheltered care facility in the Netherlands, this meant that they were not able to receive any visitors for almost 3 months. Aim: This study examines how people with an intellectual and visual disability and their families experienced the period in which it was mandated not to have any physical contact. The aim is to examine the experiences of this target group and gain insight in the way measures were taken in order to be able to advise care organizations about adequate care with respect to possible restrictive measures in the future. Methods: In-depth interviews were conducted with two groups of people: (1) fourteen people with an intellectual and visual disability, living in sheltered care facilities and (2) twelve people being relatives of residents of these same sheltered care facilities. In the interviews, the participants were questioned about their experiences with respect to the adjusted visiting regulations and with respect to the relation with their family during this period. A thematic analysis was performed first separately and then combined. Results and Discussion: A number of themes resulted from the analysis that were related to (1) the instructed regulations of the sheltered care facilities and the government; (2) the relation with family and friends; and (3) the consequences of COVID-19 and the regulations. Both relatives and residents were understanding of the difficult situation, but also expressed criticism about the chosen regulations, the communication thereof, and the practical implementation. Both groups have experienced the interruption of close contact as emotional and difficult. However, also positive consequences of the restrictions due to COVID-19 were mentioned. The results provide a list of recommendations for sheltered care facilities