Unifying dimensions in coherence relations: How various annotation frameworks are related

In this paper, we show how three often used and seemingly different discourse annotation frameworks – Penn Discourse Treebank (PDTB), Rhetorical Structure Theory (RST), and Segmented Discourse Representation Theory – can be related by using a set of unifying dimensions. These dimensions are taken from the Cognitive approach to Coherence Relations and combined with more fine-grained additional features from the frameworks themselves to yield a posited set of dimensions that can successfully map three frameworks. The resulting interface will allow researchers to find identical or at least closely related relations within sets of annotated corpora, even if they are annotated within different frameworks. Furthermore, we tested our unified dimension (UniDim) approach by comparing PDTB and RST annotations of identical news- paper texts and converting their original end label annotations of relations into the accompanying values per dimension. Subsequently, rates of overlap in the attributed values per dimension were analyzed. Results indicate that the pro- posed dimensions indeed create an interface that makes existing annotation systems “talk to each other.

Class I histone deacetylases 1, 2 and 3 are highly expressed in renal cell cancer

Background Enhanced activity of histone deacetylases (HDAC) is associated with more aggressive tumour behaviour and tumour progression in various solid tumours. The over-expression of these proteins and their known functions in malignant neoplasms has led to the development of HDAC inhibitors (HDI) as new anti-neoplastic drugs. However, little is known about HDAC expression in renal cell cancer. Methods We investigated the expression of HDAC 1, 2 and 3 in 106 renal cell carcinomas and corresponding normal renal tissue by immunohistochemistry on tissue micro arrays and correlated expression data with clinico-pathological parameters including patient survival. Results Almost 60% of renal cell carcinomas expressed the HDAC isoforms 1 and 2. In contrast, HDAC 3 was only detected in 13% of all renal tumours, with particular low expression rates in the clear cell subtype. HDAC 3 was significantly higher expressed in pT1/2 tumours in comparison to pT3/4 tumours. Expression of class I HDAC isoforms correlated with each other and with the proliferative activity of the tumours. We found no prognostic value of the expression of any of the HDAC isoforms in this tumour entity. Conclusion Class I HDAC isoforms 1 and 2 are highly expressed in renal cell cancer, while HDAC 3 shows low, histology dependent expression rates. These unexpected differences in the expression patterns suggests alternative regulatory mechanisms of class I HDACs in renal cell cancer and should be taken into account when trials with isoform selective HDI are being planned. Whether HDAC expression in renal cancers is predictive of responsiveness for HDI will have to be tested in further studies

Clients’ psychosocial communication and midwives’ verbal and nonverbal communication during prenatal counseling for anomaly screening

Objectives: This study focuses on facilitation of clients’ psychosocial communication during prenatal counseling for fetal anomaly screening. We assessed how psychosocial communication by clients is related to midwives’ psychosocial and affective communication, client-directed gaze and counseling duration. Methods: During 184 videotaped prenatal counseling consultations with 20 Dutch midwives, verbal psychosocial and affective behavior was measured by the Roter Interaction Analysis System (RIAS). We rated the duration of client-directed gaze. We performed multilevel analyses to assess the relation between clients’ psychosocial communication and midwives’ psychosocial and affective communication, client-directed gaze and counseling duration. Results: Clients’ psychosocial communication was higher if midwives’ asked more psychosocial questions and showed more affective behavior (b = 0.90; CI: 0.45–1.35; p < 0.00 and b = 1.32; CI: 0.18–2.47; p = 0.025, respectively). Clients “psychosocial communication was not related to midwives” clientdirected gaze. Additionally, psychosocial communication by clients was directly, positively related to the counseling duration (b = 0.59; CI: 0.20–099; p = 0.004). Conclusions: In contrast with our expectations, midwives’ client-directed gaze was not related with psychosocial communication of clients. Practice implications: In addition to asking psychosocial questions, our study shows that midwives’ affective behavior and counseling duration is likely to encourage client’s psychosocial communication, known to be especially important for facilitating decision-making

Recombinant Interleukin-1 Receptor antagonist is an effective first-line treatment strategy in new-onset systemic Juvenile Idiopathic Arthritis, irrespective of HLA-DRB1 background and IL1RN variants

Objective: Human leukocyte antigen (HLA)-DRB1*15:01 has been recently associated with interstitial lung disease (LD), eosinophilia, and drug reactions in systemic juvenile idiopathic arthritis (sJIA). Additionally, genetic variants in IL1RN have been linked to poor response to anakinra. We sought to reproduce these findings in a prospective cohort study of patients with new-onset sJIA treated with anakinra as first-line therapy. Methods: HLA and IL1RN risk alleles were identified via whole-genome sequencing. Treatment responses and complications were compared between carriers versus noncarriers. Results: Seventeen of 65 patients (26%) carried HLA-DRB1*15:01, comparable with the general population, and there was enrichment for HLA-DRB1*11:01, a known risk locus for sJIA. The rates of clinical inactive disease (CID) at 6 months, 1 year, and 2 years were generally high, irrespective of HLA-DRB1 or IL1RN variants, but significantly lower in carriers of an HLA-DRB1*11:01 allele. One patient, an HLA-DRB1*15:01 carrier, developed sJIA-LD. Of the three patients with severe drug reactions to biologics, one carried HLA-DRB1*15:01. The prevalence of eosinophilia did not significantly differ between HLA-DRB1*15:01 carriers and noncarriers at disease onset (6.2% vs 14.9%, P = 0.67) nor after the start of anakinra (35.3% vs 37.5% in the first 2 years of disease). Conclusion: We observed high rates of CID using anakinra as first-line treatment irrespective of HLA-DRB1 or IL1RN variants. Only one of the 17 HLA-DRB1*15:01 carriers developed sJIA-LD, and of the three patients with drug reactions to biologics, only one carried HLA-DRB1*15:01. Although thorough monitoring for the development of drug hypersensitivity and refractory disease courses in sJIA, including sJIA-LD, remains important, our data support the early start of biologic therapy in patients with new-onset sJIA irrespective of HLA-DRB1 background or IL1RN variants. (Figure presented.)

Obtaining smoothly navigable approximation sets in bi-objective multi-modal optimization

Even if a Multi-modal Multi-Objective Evolutionary Algorithm (MMOEA) is designed to find solutions well spread over all locally optimal approximation sets of a Multi-modal Multi-objective Optimization Problem (MMOP), there is a risk that the found set of solutions is not smoothly navigable because the solutions belong to various niches, reducing the insight for decision makers. To tackle this issue, a new MMOEAs is proposed: the Multi-Modal Bézier Evolutionary Algorithm (MM-BezEA), which produces approximation sets that cover individual niches and exhibit inherent decision-space smoothness as they are parameterized by Bézier curves. MM-BezEA combines the concepts behind the recently introduced BezEA and MO-HillVallEA to find all locally optimal approximation sets. When benchmarked against the MMOEAs MO_Ring_PSO_SCD and MO-HillVallEA on MMOPs with linear Pareto sets, MM-BezEA was found to perform best in terms of best hypervolume

From Genome-Wide Association Studies to Cardiac Electrophysiology: Through the Maze of Biological Complexity: Through the Maze of Biological Complexity

Genome Wide Association Studies (GWAS) have provided an enormous amount of data on genomic loci associated with cardiac electrophysiology and arrhythmias. Clinical relevance, however, remains unclear since GWAS do not provide a mechanistic explanation for this association. Determining the electrophysiological relevance of variants for arrhythmias would aid development of risk stratification models for patients with arrhythmias. In this review, we give an overview of genetic variants related to ECG intervals and arrhythmogenic pathologies and discuss how these variants may influence cardiac electrophysiology and the occurrence of arrhythmias

Keeping your best options open with AI-based treatment planning in prostate and cervix brachytherapy

PURPOSE: Without a clear definition of an optimal treatment plan, no optimization model can be perfect. Therefore, instead of automatically finding a single “optimal” plan, finding multiple, yet different near-optimal plans, can be an insightful approach to support radiation oncologists in finding the plan they are looking for. METHODS AND MATERIALS: BRIGHT is a flexible AI-based optimization method for brachytherapy treatment planning that has already been shown capable of finding high-quality plans that trade-off target volume coverage and healthy tissue sparing. We leverage the flexibility of BRIGHT to find plans with similar dose-volume criteria, yet different dose distributions. We further describe extensions that facilitate fast plan adaptation should planning aims need to be adjusted, and straightforwardly allow incorporating hospital-specific aims besides standard protocols. RESULTS: Results are obtained for prostate (n=12) and cervix brachytherapy (n=36). We demonstrate the possible differences in dose distribution for optimized plans with equal dosevolume criteria. We furthermore demonstrate that adding hospital-specific aims enables adhering to hospital-specific practice while still being able to automatically create cervix plans that more often satisfy the EMBRACE-II protocol than clinical practice. Finally, we illustrate the feasibility of fast plan adaptation. CONCLUSIONS: Methods such as BRIGHT enable new ways to construct high-quality treatment plans for brachytherapy while offering new insights by making explicit the options one has. In particular, it becomes possible to present to radiation oncologists a manageable set of alternative plans that, from an optimization perspective are equally good, yet differ in terms of coverage-sparing trade-offs and shape of the dose distribution</p