1052-2 Expert System Aid in Differentiating Among Paroxysmal Supraventricular Tachycardias

The differentiation between atrioventricular reciprocating tachycardia via an accessory pathway (AVRT) AV nodal reentrant tachycardia (AVNRT) and atrial tachycardia (AT) in paroxysmal supraventricular tachycardia may be helpful in guiding pharmacologic therapy and in identifying patients for radiofrequency catheter ablation. To help in this differentiation, an expert system was developed using a commercially-available expert system shell (EXSY'S). A simplified version of this system was designed to run on a palm-top computer. Both programs use the MS-DOS operating system. The expert system is rule-based and assigns probability values to the goal states through the process of backward chaining. The goal states for this expert system were AVRT, AVNRT, and AT. The user is queried for the presence of various abnormalities on the presenting EKG (P wave location, ORS alternans, pseudo r wave in lead V1, pseudo S wave in the inferior leads), comparison with previous EKG's (presence of pre-excitation) and the effect of vagal manueuvers or adenosine infusion on the tachycardia. From published data, each abnormality is assigned a probability based on the positive predictive value of the abnormality for AVRT, AVNRT and AT. By combining the positive predictive values, the expert system assigns a final probability for AVRT, AVNRT and AT.This expert system may be useful as a diagnostic tool and a teaching aid in the differentiation between AVRT, AVNRT and AT in paroxysmal supraventricular tachycardia

The utility of image descriptions in the initial stages of vision: a case study of printed text

Vision research has made very substantial progress towards understanding how we see. It is one area of psychology where the three-way thrust of behavioural measurements (psychophysics), brain imaging, and computational studies have been combined quite routinely for some years. The purpose of this paper is to demonstrate a relatively unusual form of computational modelling which we characterise as involving image descriptions. Image descriptions are statements about structures in images and relationships between structures. Most modelling in vision is either conceived in fairly abstract terms, or is done at the level of images. Neither is entirely satisfactory, and image descriptions are a simple formulation of age-old ideas about a vocabulary of image features that are detected and parameterized from actual digital images. For our example, we use the domain of the visual perception of printed text. This is an area that has been characterized by thorough, robust psychophysical experiments. The fundamental requirements of visual processing in this domain are: grouping of some parts if the image into words; at the same time segmenting words from each other. We show how these are readily understood in terms of our model of image descriptions, and show quantitatively that typographical practice, refined over centuries, is about optimum for the visual system at least as represented by our model. In addition, we show that the same notion of image descriptions could, in principle, support word recognition in certain circumstances

Identifying colorectal cancer caused by biallelic MUTYH pathogenic variants using tumor mutational signatures

Carriers of germline biallelic pathogenic variants in the MUTYH gene have a high risk of colorectal cancer. We test 5649 colorectal cancers to evaluate the discriminatory potential of a tumor mutational signature specific to MUTYH for identifying biallelic carriers and classifying variants of uncertain clinical significance (VUS). Using a tumor and matched germline targeted multi-gene panel approach, our classifier identifies all biallelic MUTYH carriers and all known non-carriers in an independent test set of 3019 colorectal cancers (accuracy = 100% (95% confidence interval 99.87-100%)). All monoallelic MUTYH carriers are classified with the non-MUTYH carriers. The classifier provides evidence for a pathogenic classification for two VUS and a benign classification for five VUS. Somatic hotspot mutations KRAS p.G12C and PIK3CA p.Q546K are associated with colorectal cancers from biallelic MUTYH carriers compared with non-carriers (p = 2 x 10(-23) and p = 6 x 10(-11), respectively). Here, we demonstrate the potential application of mutational signatures to tumor sequencing workflows to improve the identification of biallelic MUTYH carriers. Germline biallelic pathogenic MUTYH variants predispose patients to colorectal cancer (CRC); however, approaches to identify MUTYH variant carriers are lacking. Here, the authors evaluated mutational signatures that could distinguish MUTYH carriers in large CRC cohorts, and found MUTYH-associated somatic mutations

Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival

Colorectal cancer (CRC) is a biologically heterogeneous disease. To characterize its mutational profile, we conduct targeted sequencing of 205 genes for 2,105 CRC cases with survival data. Our data shows several findings in addition to enhancing the existing knowledge of CRC. We identify PRKCI, SPZ1, MUTYH, MAP2K4, FETUB, and TGFBR2 as additional genes significantly mutated in CRC. We find that among hypermutated tumors, an increased mutation burden is associated with improved CRC-specific survival (HR=0.42, 95% CI: 0.21-0.82). Mutations in TP53 are associated with poorer CRC-specific survival, which is most pronounced in cases carrying TP53 mutations with predicted 0% transcriptional activity (HR=1.53, 95% CI: 1.21-1.94). Furthermore, we observe differences in mutational frequency of several genes and pathways by tumor location, stage, and sex. Overall, this large study provides deep insights into somatic mutations in CRC, and their potential relationships with survival and tumor features. Large scale sequencing study is of paramount importance to unravel the heterogeneity of colorectal cancer. Here, the authors sequenced 205 cancer genes in more than 2000 tumours and identified additional mutated driver genes, determined that mutational burden and specific mutations in TP53 are associated with survival odds

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Momenta Biennale : Quand la nature ressent = Sensing Nature

" Sensing Nature, the title for the 17th edition of MOMENTA, can be read in multiple ways. On the one hand, it assumes a human who is sensing nature, perhaps holding a blueberry picked in a forest, exposed to various modes of perception: sight, smell, taste, hearing, and touch. None of us sense in the same way, and our diverse and differently abled bodies perceive and feel differently. On the other hand, the title assumes nature sensing back. Our doings register like sunlight bleaching the colour of driftwood over time or imprinting itself on the retina of an exposed eye. In acknowledging this reciprocity, the biennale works toward decentring the often- foregrounded European-Enlightenment human creator of knowl- edge concerning the natural world. It makes room for stories that dwell in the blurred boundaries between culture and nature, weaving in both human and nonhuman modes of knowing. Sensing Nature recognizes that we are in relation with nature, that we are of nature. " -- Publisher's website