495 research outputs found
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Activity of Genes with Functions in Human Williams-Beuren Syndrome Is Impacted by Mobile Element Insertions in the Gray Wolf Genome.
In canines, transposon dynamics have been associated with a hyper-social behavioral syndrome, although the functional mechanism has yet to be described. We investigate the epigenetic and transcriptional consequences of these behavior-associated mobile element insertions (MEIs) in dogs and Yellowstone gray wolves. We posit that the transposons themselves may not be the causative feature; rather, their transcriptional regulation may exert the functional impact. We survey four outlier transposons associated with hyper-sociability, with the expectation that they are targeted for epigenetic silencing. We predict hyper-methylation of MEIs, suggestive that the epigenetic silencing of and not the MEIs themselves may be driving dysregulation of nearby genes. We found that transposon-derived sequences are significantly hyper-methylated, regardless of their copy number or species. Further, we have assessed transcriptome sequence data and found evidence that MEIs impact the expression levels of six genes (WBSCR17, LIMK1, GTF2I, WBSCR27, BAZ1B, and BCL7B), all of which have known roles in human Williams-Beuren syndrome due to changes in copy number, typically hemizygosity. Although further evidence is needed, our results suggest that a few insertions alter local expression at multiple genes, likely through a cis-regulatory mechanism that excludes proximal methylation
Rapid keratitis and perforation after corneal collagen cross-linking
© 2020 Purpose: To describe a case of rapid keratitis and corneal perforation after epithelium off collagen cross-linking. Observations: We report a case of a 17-year-old male who underwent collagen cross-linking with the protocol and device approved by the United States Food and Drug Administration (FDA) that developed a corneal infiltrate 3 days after the procedure. He later developed corneal thinning and perforation on day 5 requiring the use of cyanoacrylate glue and a Kontur lens. Despite initial improvement in the infiltrate with fortified antibiotics he later had leakage of aqueous around the glue and a flat chamber requiring an emergent penetrating keratoplasty on postoperative day 16. Conclusion and importance: While collagen cross-linking has been very effective for treating keratoconus and is being recommended more frequently since FDA approval in the United States, severe complications such as corneal perforation requiring early transplant can still occur
The Missing Indicator Method: From Low to High Dimensions
Missing data is common in applied data science, particularly for tabular data
sets found in healthcare, social sciences, and natural sciences. Most
supervised learning methods only work on complete data, thus requiring
preprocessing such as missing value imputation to work on incomplete data sets.
However, imputation alone does not encode useful information about the missing
values themselves. For data sets with informative missing patterns, the Missing
Indicator Method (MIM), which adds indicator variables to indicate the missing
pattern, can be used in conjunction with imputation to improve model
performance. While commonly used in data science, MIM is surprisingly
understudied from an empirical and especially theoretical perspective. In this
paper, we show empirically and theoretically that MIM improves performance for
informative missing values, and we prove that MIM does not hurt linear models
asymptotically for uninformative missing values. Additionally, we find that for
high-dimensional data sets with many uninformative indicators, MIM can induce
model overfitting and thus test performance. To address this issue, we
introduce Selective MIM (SMIM), a novel MIM extension that adds missing
indicators only for features that have informative missing patterns. We show
empirically that SMIM performs at least as well as MIM in general, and improves
MIM for high-dimensional data. Lastly, to demonstrate the utility of MIM on
real-world data science tasks, we demonstrate the effectiveness of MIM and SMIM
on clinical tasks generated from the MIMIC-III database of electronic health
records
Are chimpanzees really so poor at understanding imperative pointing? Some new data and an alternative view of canine and ape social cognition
There is considerable interest in comparative research on different species’ abilities to respond to human communicative cues such as gaze and pointing. It has been reported that some canines perform significantly better than monkeys and apes on tasks requiring the comprehension of either declarative or imperative pointing and these differences have been attributed to domestication in dogs. Here we tested a sample of chimpanzees on a task requiring comprehension of an imperative request and show that, though there are considerable individual differences, the performance by the apes rival those reported in pet dogs. We suggest that small differences in methodology can have a pronounced influence on performance on these types of tasks. We further suggest that basic differences in subject sampling, subject recruitment and rearing experiences have resulted in a skewed representation of canine abilities compared to those of monkeys and apes
Ontogeny vs. phylogeny in Primate/Canid comparisons: a meta-analysis of the object choice task
The Object Choice Task (OCT) is a widely used paradigm with which researchers measure the ability of a subject to comprehend deictic (directional) cues, such as pointing gestures and eye gaze. There is a widespread belief that nonhuman primates evince only a weak capacity to use deictic cues; in contrast, domestic dogs (Canis familiaris) tend to demonstrate high success rates. This pattern of canid superiority has been taken to support the Domestication Hypothesis, which posits enhancing effects of artificial selection on the sociocognitive abilities of dogs and humans. Here we review nearly two decades of published findings, using variants of the OCT. We find systematic confounds with species classification in task-relevant preparation of the subjects, in the imposition of a barrier between reward and subject, and in the specific deictic cues used to indicate the location of hidden objects. Thus, the widespread belief that dogs outperform primates on OCTs is undermined by the systematic procedural differences in the assessments of these skills, differences that are confounded with taxonomic classification
Prasugrel Versus Clopidogrel in Patients With ST-Segment Elevation Myocardial Infarction According to Timing of Percutaneous Coronary Intervention A TRITON–TIMI 38 Subgroup Analysis (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel–Thrombolysis In Myocardial Infarction 38)
ObjectivesThis study sought to evaluate the efficacy of prasugrel versus clopidogrel in ST-segment elevation myocardial infarction (STEMI) by the timing of percutaneous coronary intervention (PCI).BackgroundTreatment strategies and outcomes for patients with STEMI may differ when treated with primary compared with secondary PCI.MethodsSTEMI patients in the TRITON–TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel–Thrombolysis In Myocardial Infarction 38) were randomized to prasugrel or clopidogrel on presentation if primary PCI was intended or later during secondary PCI. Primary PCI was defined as within 12 h of symptom onset. The primary endpoint was cardiovascular death, myocardial infarction (MI), or stroke. Because periprocedural MI is difficult to assess in the setting of STEMI, we performed analyses excluding these events.ResultsReductions in the primary endpoint with prasugrel versus clopidogrel (hazard ratio [HR]: 0.79; 95% confidence interval [CI]: 0.65 to 0.97; p = 0.022) were consistent between primary and secondary PCI patients at 15 months (HR: 0.89; 95% CI: 0.69 to 1.13 vs. HR: 0.65; 95% CI: 0.46 to 0.93; p interaction = 0.15). However, a tendency toward a difference in treatment effect at 30 days (HR: 0.68; 95% CI: 0.54 to 0.87; p = 0.002) was observed between primary and secondary PCI patients (HR: 0.81; 95% CI: 0.60 to 1.09 vs. HR: 0.51; 95% CI: 0.34 to 0.76; p interaction = 0.06). When periprocedural MI was excluded, the efficacy of prasugrel remained consistent among primary and secondary PCI patients at 30 days (HR: 0.53; 95% CI: 0.34 to 0.81 vs. HR: 0.44; 95% CI: 0.22 to 0.88; p interaction = 0.68) and 15 months (HR: 0.76; 95% CI: 0.56 to 1.03 vs. HR: 0.75; 95% CI: 0.46 to 1.21; p interaction = 0.96).ConclusionsThe efficacy of prasugrel versus clopidogrel was consistent irrespective of the timing of PCI, particularly in preventing nonprocedural events. (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction 38; NCT00097591
The plight of the sense-making ape
This is a selective review of the published literature on object-choice tasks, where participants use directional cues to find hidden objects. This literature comprises the efforts of researchers to make sense of the sense-making capacities of our nearest living relatives. This chapter is written to highlight some nonsensical conclusions that frequently emerge from this research. The data suggest that when apes are given approximately the same sense-making opportunities as we provide our children, then they will easily make sense of our social signals. The ubiquity of nonsensical contemporary scientific claims to the effect that humans are essentially--or inherently--more capable than other great apes in the understanding of simple directional cues is, itself, a testament to the power of preconceived ideas on human perception
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Interspecific communication from people to horses (Equus ferus caballus) is influenced by different horsemanship training styles
The ability of many domesticated animals to follow human pointing gestures to locate hidden food has led to scientific debate on the relative importance of domestication and individual experience on the origins and development of this capacity. To further explore this question we examined the influence of different prior training histories/methods on the ability of horses (Equus ferus caballus) to follow a momentary distal point. Ten horses previously trained using one of two methods (Parelli Natural Horsemanship or traditional horse training) were tested using a standard object choice task. The results show that neither group of horses was able to follow the momentary distal point initially. However, after more experience with the point, horses previously trained using Parelli’s Natural Horsemanship method learned to follow momentary distal points significantly faster than those previously trained with traditional methods. The poor initial performance of horses on distal pointing tasks, coupled with the finding that prior training history and experimental experience can lead to success on this task, fails to support the predictions of the Domestication Hypothesis, and instead lends support to the Two-Stage Hypothesis.This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by the American Psychological Association and can be found at: http://www.apa.org/pubs/journals/com/ This article may not exactly replicate the final version published in the APA journal. It is not the copy of record.Keywords: Momentary distal point, Object-choice task, Parelli Natural Horsemanship, Social cognition, Traditional horse training, Learning, Equus ferus caballu
Prevalence of diabetic and impact on cardiovascular events and mortality in patients with chronic coronary syndromes, across multiple geographical regions and ethnicities
Background: In contrast with the setting of acute myocardial infarction, there are limited data regarding the impact of diabetes mellitus on clinical outcomes in contemporary cohorts of patients with chronic coronary syndromes. We aimed to investigate the prevalence and prognostic impact of diabetes according to geographical regions and ethnicity. Methods: CLARIFY is an observational registry of patients with chronic coronary syndromes, enrolled across 45 countries in Europe, Asia, America, Middle East, Australia and Africa in 2009-2010, and followed-up yearly for 5 years. Chronic coronary syndromes were defined by ≥1 of the following criteria: prior myocardial infarction, evidence of coronary stenosis >50%, proven symptomatic myocardial ischemia, or prior revascularisation procedure. Results: Among 32,694patients, 9502 (29%) had diabetes, with a regional prevalence ranging from below 20% in Northern Europe to approximately 60% in the Gulf countries. In a multivariable-adjusted Cox proportional hazards model, diabetes was associated with increased risks for the primary outcome(cardiovascular death, myocardial infarction or stroke)with an adjusted hazard ratio of1.28(95% CI 1.18-1.39) and for all secondary outcomes (all-cause and cardiovascular mortality, myocardial infarction, stroke, heart failure and coronary revascularization). Differences on outcomes according to geography and ethnicity were modest. Conclusion: In patients with chronic coronary syndromes, diabetes is independently associated with mortality and cardiovascular events, including heart failure, which is not accounted by demographics, prior medical history, left ventricular ejection fraction, or use of secondary prevention medication. This is observed across multiple geographic regions and ethnicities, despite marked disparities in the prevalence of diabetes
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