Shading Beats Binocular Disparity in Depth from Luminance Gradients: Evidence against a Maximum Likelihood Principle for Cue Combination

Perceived depth is conveyed by multiple cues, including binocular disparity and luminance shading. Depth perception from luminance shading information depends on the perceptual assumption for the incident light, which has been shown to default to a diffuse illumination assumption. We focus on the case of sinusoidally corrugated surfaces to ask how shading and disparity cues combine defined by the joint luminance gradients and intrinsic disparity modulation that would occur in viewing the physical corrugation of a uniform surface under diffuse illumination. Such surfaces were simulated with a sinusoidal luminance modulation (0.26 or 1.8 cy/deg, contrast 20%-80%) modulated either in-phase or in opposite phase with a sinusoidal disparity of the same corrugation frequency, with disparity amplitudes ranging from 0’-20’. The observers’ task was to adjust the binocular disparity of a comparison random-dot stereogram surface to match the perceived depth of the joint luminance/disparitymodulated corrugation target. Regardless of target spatial frequency, the perceived target depth increased with the luminance contrast and depended on luminance phase but was largely unaffected by the luminance disparity modulation. These results validate the idea that human observers can use the diffuse illumination assumption to perceive depth from luminance gradients alone without making an assumption of light direction. For depth judgments with combined cues, the observers gave much greater weighting to the luminance shading than to the disparity modulation of the targets. The results were not well-fit by a Bayesian cue-combination model weighted in proportion to the variance of the measurements for each cue in isolation. Instead, they suggest that the visual system uses disjunctive mechanisms to process these two types of information rather than combining them according to their likelihood ratios

Homoplastic microinversions and the avian tree of life

Background: Microinversions are cytologically undetectable inversions of DNA sequences that accumulate slowly in genomes. Like many other rare genomic changes (RGCs), microinversions are thought to be virtually homoplasyfree evolutionary characters, suggesting that they may be very useful for difficult phylogenetic problems such as the avian tree of life. However, few detailed surveys of these genomic rearrangements have been conducted, making it difficult to assess this hypothesis or understand the impact of microinversions upon genome evolution. Results: We surveyed non-coding sequence data from a recent avian phylogenetic study and found substantially more microinversions than expected based upon prior information about vertebrate inversion rates, although this is likely due to underestimation of these rates in previous studies. Most microinversions were lineage-specific or united well-accepted groups. However, some homoplastic microinversions were evident among the informative characters. Hemiplasy, which reflects differences between gene trees and the species tree, did not explain the observed homoplasy. Two specific loci were microinversion hotspots, with high numbers of inversions that included both the homoplastic as well as some overlapping microinversions. Neither stem-loop structures nor detectable sequence motifs were associated with microinversions in the hotspots. Conclusions: Microinversions can provide valuable phylogenetic information, although power analysis indicate

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Acute systemic and coronary hemodynamic and serologic responses to cigarette smoking in long-term smokers with atherosclerotic coronary artery disease

Previous studies suggested that cigarette smoking 1) inhibits an increase in coronary blood flow that should occur with increased myocardial oxygen demands, and 2) alters thromboxane and prostacyclin production, causing vasoconstriction and platelet aggregation. In 38 smokers (26 men and 12 women, aged 50 ± 8 years [mean ± standard deviation]) with coronary artery disease, systemic and coronary hemodynamic and serologic variables were measured before and after smoking two cigarettes (in 8 to 10 minutes) (21 patients) or 8 to 10 minutes without smoking (17 patients; control group). No variable changed in the control group. Smoking increased (p < 0.05) heart rate-systolic pressure product, cardiac output and maximal first derivative of left ventricular pressure (dP/dt) without significantly changing the coronary sinus concentrations of thromboxane B2 or 6-keto-prostaglandin F1α (the stable metabolites of thromboxane A2 and prostacyclin, respectively). Smoking did not increase coronary flow in 6 of 11 patients with greater than 70% stenosis of the proximal left anterior descending or circumflex coronary artery, or both,whereas it caused an increase in coronary flow in all 10 patients without proximal stenoses (p = 0.006). To determine if smoking altered the response of coronary flow to increased myocardial oxygen demands, 10 smokers (5 men and 5 women, aged 48 ± 9 years) underwent atrial pacing for 5 minutes followed 15 minutes later by atrial pacing for 5 minutes during smoking. In the five patients without proximal left coronary artery stenoses, coronary flow increased 26 ± 29 ml/min with pacing and 45 ± 21 ml/min with pacing/smoking (p = 0.018). In contrast, in the five patients with proximal stenoses, coronary flow increased 39 ± 24 ml/min with pacing, but only 36 ± 16 ml/min with pacing/smoking (p = NS). Thus, in smokers with coronary artery disease, smoking increases myocardial oxygen demands. However, in some individuals with severe proximal stenoses of the left coronary artery, it may induce no change or cause a decrease in coronary blood flow. The net effect of smoking on coronary blood flow appears to be influenced by the location and severity of atherosclerotic coronary artery disease

Exploring Pandora's Box: potential and pitfalls of low coverage genome surveys for evolutionary biology

High throughput sequencing technologies are revolutionizing genetic research. With this ‘‘rise of the machines’’, genomic sequences can be obtained even for unknown genomes within a short time and for reasonable costs. This has enabled evolutionary biologists studying genetically unexplored species to identify molecular markers or genomic regions of interest (e.g. micro- and minisatellites, mitochondrial and nuclear genes) by sequencing only a fraction of the genome. However, when using such datasets from non-model species, it is possible that DNA from non-target contaminant species such as bacteria, viruses, fungi, or other eukaryotic organisms may complicate the interpretation of the results. In this study we analysed 14 genomic pyrosequencing libraries of aquatic non-model taxa from four major evolutionary lineages. We quantified the amount of suitable micro- and minisatellites, mitochondrial genomes, known nuclear genes and transposable elements and searched for contamination from various sources using bioinformatic approaches. Our results show that in all sequence libraries with estimated coverage of about 0.02–25%, many appropriate micro- and minisatellites, mitochondrial gene sequences and nuclear genes from different KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways could be identified and characterized. These can serve as markers for phylogenetic and population genetic analyses. A central finding of our study is that several genomic libraries suffered from different biases owing to non-target DNA or mobile elements. In particular, viruses, bacteria or eukaryote endosymbionts contributed significantly (up to 10%) to some of the libraries analysed. If not identified as such, genetic markers developed from high-throughput sequencing data for non-model organisms may bias evolutionary studies or fail completely in experimental tests. In conclusion, our study demonstrates the enormous potential of low-coverage genome survey sequences and suggests bioinformatic analysis workflows. The results also advise a more sophisticated filtering for problematic sequences and non-target genome sequences prior to developing markers

The use of tissue-type plasminogen activator for acute myocardial infarction in the elderly: Results from thrombolysis in myocardial infarction phase I, open label studies and the thrombolysis in myocardial infarction phase II pilot study

AbstractThe impact of age on hospital mortality, incidence of major hemorrhagic events and transfusion requirements was examined in 756 patients with acute myocardial infarction enrolled in the Thrombolysis in Myocardial Infarction (TIMI) Phase I, open label studies and the TIMI Phase II pilot study. The mortality rate significantly increased with age and was 3.5%, 11.5% and 12% in patients <65, 65 to 69 and 70 to 76 years of age, respectively (p < 0.001). Logistic regression analyses selected female gender, diabetes mellitus, extensive coronary artery disease, history of congestive heart failure, continuing chest pain immediately after recombinant tissue-type plasminogen activator (rt-PA) administration, low systolic blood pressure at the time of admission and advanced age as variables predictive of in-hospital death.The incidence of major hemorrhagic events among patients not undergoing cardiac surgery during hospitalization was 8.7%, 14.5% and 24.7% in patients aged <65, 65 to 69 and ⩾ 70 years, respectively (p < 0.001). The majority of hemorrhages were secondary to cardiac catheterization or puncture wounds. Variables related to a major hemorrhagic event included protocol, age, rt-PA dose/kg body weight and elevated diastolic blood pressure on admission. Of five intracranial bleeding events, three occurred in patients >65 years. Transfusion requirements significantly increased with age (p < 0.001). Reperfusion status at 90 min in the TIMI Phase I and open label studies A to C was similar in the three age groups studied and ranged from 60% to 71%a.Thus, a strategy of early cardiac catheterization in older patients with acute myocardial infarction treated with thrombolytic therapy is associated with an increased hospital mortality rate and incidence of bleeding compared with findings in younger patients. A randomized placebocontrolled trial appears to be needed to determine safety and efficacy of rt-PA therapy in patients >76 years