Perceptually Uniform Construction of Illustrative Textures

Illustrative textures, such as stippling or hatching, were predominantly used as an alternative to conventional Phong rendering. Recently, the potential of encoding information on surfaces or maps using different densities has also been recognized. This has the significant advantage that additional color can be used as another visual channel and the illustrative textures can then be overlaid. Effectively, it is thus possible to display multiple information, such as two different scalar fields on surfaces simultaneously. In previous work, these textures were manually generated and the choice of density was unempirically determined. Here, we first want to determine and understand the perceptual space of illustrative textures. We chose a succession of simplices with increasing dimensions as primitives for our textures: Dots, lines, and triangles. Thus, we explore the texture types of stippling, hatching, and triangles. We create a range of textures by sampling the density space uniformly. Then, we conduct three perceptual studies in which the participants performed pairwise comparisons for each texture type. We use multidimensional scaling (MDS) to analyze the perceptual spaces per category. The perception of stippling and triangles seems relatively similar. Both are adequately described by a 1D manifold in 2D space. The perceptual space of hatching consists of two main clusters: Crosshatched textures, and textures with only one hatching direction. However, the perception of hatching textures with only one hatching direction is similar to the perception of stippling and triangles. Based on our findings, we construct perceptually uniform illustrative textures. Afterwards, we provide concrete application examples for the constructed textures.Comment: 11 pages, 15 figures, to be published in IEEE Transactions on Visualization and Computer Graphic

Characteristics of hepatitis C virus resistance in an international cohort after a decade of direct-acting antivirals

BACKGROUND & AIMS Direct-acting antiviral (DAA) regimens provide a cure in >95% of patients with chronic HCV infection. However, in some patients in whom therapy fails, resistance-associated substitutions (RASs) can develop, limiting retreatment options and risking onward resistant virus transmission. In this study, we evaluated RAS prevalence and distribution, including novel NS5A RASs and clinical factors associated with RAS selection, among patients who experienced DAA treatment failure. METHODS SHARED is an international consortium of clinicians and scientists studying HCV drug resistance. HCV sequence linked metadata from 3,355 patients were collected from 22 countries. NS3, NS5A, and NS5B RASs in virologic failures, including novel NS5A substitutions, were examined. Associations of clinical and demographic characteristics with RAS selection were investigated. RESULTS The frequency of RASs increased from its natural prevalence following DAA exposure: 37% to 60% in NS3, 29% to 80% in NS5A, 15% to 22% in NS5B for sofosbuvir, and 24% to 37% in NS5B for dasabuvir. Among 730 virologic failures, most were treated with first-generation DAAs, 94% had drug resistance in ≥1 DAA class: 31% single-class resistance, 42% dual-class resistance (predominantly against protease and NS5A inhibitors), and 21% triple-class resistance. Distinct patterns containing ≥2 highly resistant RASs were common. New potential NS5A RASs and adaptive changes were identified in genotypes 1a, 3, and 4. Following DAA failure, RAS selection was more frequent in older people with cirrhosis and those infected with genotypes 1b and 4. CONCLUSIONS Drug resistance in HCV is frequent after DAA treatment failure. Previously unrecognized substitutions continue to emerge and remain uncharacterized. LAY SUMMARY Although direct-acting antiviral medications effectively cure hepatitis C in most patients, sometimes treatment selects for resistant viruses, causing antiviral drugs to be either ineffective or only partially effective. Multidrug resistance is common in patients for whom DAA treatment fails. Older patients and patients with advanced liver diseases are more likely to select drug-resistant viruses. Collective efforts from international communities and governments are needed to develop an optimal approach to managing drug resistance and preventing the transmission of resistant viruses

Characteristics of hepatitis C virus resistance in an international cohort after a decade of direct-acting antivirals

Virologic failure; Hepatitis CFracaso virológico; Hepatitis CFracàs virològic; Hepatitis CBackground & Aims Direct-acting antiviral (DAA) regimens provide a cure in >95% of patients with chronic HCV infection. However, in some patients in whom therapy fails, resistance-associated substitutions (RASs) can develop, limiting retreatment options and risking onward resistant virus transmission. In this study, we evaluated RAS prevalence and distribution, including novel NS5A RASs and clinical factors associated with RAS selection, among patients who experienced DAA treatment failure. Methods SHARED is an international consortium of clinicians and scientists studying HCV drug resistance. HCV sequence linked metadata from 3,355 patients were collected from 22 countries. NS3, NS5A, and NS5B RASs in virologic failures, including novel NS5A substitutions, were examined. Associations of clinical and demographic characteristics with RAS selection were investigated. Results The frequency of RASs increased from its natural prevalence following DAA exposure: 37% to 60% in NS3, 29% to 80% in NS5A, 15% to 22% in NS5B for sofosbuvir, and 24% to 37% in NS5B for dasabuvir. Among 730 virologic failures, most were treated with first-generation DAAs, 94% had drug resistance in ≥1 DAA class: 31% single-class resistance, 42% dual-class resistance (predominantly against protease and NS5A inhibitors), and 21% triple-class resistance. Distinct patterns containing ≥2 highly resistant RASs were common. New potential NS5A RASs and adaptive changes were identified in genotypes 1a, 3, and 4. Following DAA failure, RAS selection was more frequent in older people with cirrhosis and those infected with genotypes 1b and 4. Conclusions Drug resistance in HCV is frequent after DAA treatment failure. Previously unrecognized substitutions continue to emerge and remain uncharacterized.The initial SHARED development was funded in part by Merck and a User Partnership Program grant from Genome British Columbia to P.R.H and A.Y.M.H (UPP029). The Kirby Institute is funded by the Australian Government Department of Health and Ageing. The views expressed in this publication do not necessarily represent the position of the Australian (or any other) Government. C.R. and J.G. are supported by an NHMRC Investigator Grant (nos. 1173666, 1176131). An NHMRC Program Grant supported RAS testing and data collection by M.W.D. (1053206) and small grants from the Australian Centre for HIV and Hepatitis Virology Research, The University of Sydney, Western Sydney Local Health District Research Education Network, and the Robert W. Storr bequest to the Sydney Medical Foundation (University of Sydney). S.P. received personal fees from Gilead Sciences. Regarding the Italian data, the work was supported in part by the Italian Ministry of Instruction, University and Research (MIUR) (Bandiera InterOmics Protocollo PB05 1°), by the Italian Ministry of Health (RF-2016-02362422), and by Aviralia and Vironet C Foundations

Selective nitrogen adsorption via backbonding in a metal-organic framework with exposed vanadium sites.

Industrial processes prominently feature π-acidic gases, and an adsorbent capable of selectively interacting with these molecules could enable important chemical separations1-4. Biological systems use accessible, reducing metal centres to bind and activate weakly π-acidic species, such as N2, through backbonding interactions5-7, and incorporating analogous moieties into a porous material should give rise to a similar adsorption mechanism for these gaseous substrates8. Here, we report a metal-organic framework featuring exposed vanadium(II) centres capable of back-donating electron density to weak π acids to successfully target π acidity for separation applications. This adsorption mechanism, together with a high concentration of available adsorption sites, results in record N2 capacities and selectivities for the removal of N2 from mixtures with CH4, while further enabling olefin/paraffin separations at elevated temperatures. Ultimately, incorporating such π-basic metal centres into porous materials offers a handle for capturing and activating key molecular species within next-generation adsorbents

Opioid Receptor Probes Derived from Cycloaddition of the Hallucinogen Natural Product Salvinorin A

As part of our continuing efforts toward more fully understanding the structure−activity relationships of the neoclerodane diterpene salvinorin A, we report the synthesis and biological characterization of unique cycloadducts through [4+2] Diels−Alder cycloaddition. Microwave-assisted methods were developed and successfully employed, aiding in functionalizing the chemically sensitive salvinorin A scaffold. This demonstrates the first reported results for both cycloaddition of the furan ring and functionalization via microwave-assisted methodology of the salvinorin A skeleton. The cycloadducts yielded herein introduce electron-withdrawing substituents and bulky aromatic groups into the C-12 position. Kappa opioid (KOP) receptor space was explored through aromatization of the bent oxanorbornadiene system possessed by the cycloadducts to a planar phenyl ring system. Although dimethyl- and diethylcarboxylate analogues 5 and 6 retain some affinity and selectivity for KOP receptors and are full agonists, their aromatized counterparts 13 and 14 have reduced affinity for KOP receptors. The methods developed herein signify a novel approach toward rapidly probing the structure−activity relationships of furan-containing natural products

Meeting the challenges of myocarditis: New opportunities for prevention, detection, and intervention-a report from the 2021 National Heart, Lung, and Blood Institute workshop

The National Heart, Lung, and Blood Institute (NHLBI) convened a workshop of international experts to discuss new research opportunities for the prevention, detection, and intervention of myocarditis in May 2021. These experts reviewed the current state of science and identified key gaps and opportunities in basic, diagnostic, translational, and therapeutic frontiers to guide future research in myocarditis. In addition to addressing community-acquired myocarditis, the workshop also focused on emerging causes of myocarditis including immune checkpoint inhibitors and SARS-CoV-2 related myocardial injuries and considered the use of systems biology and artificial intelligence methodologies to define workflows to identify novel mechanisms of disease and new therapeutic targets. A new priority is the investigation of the relationship between social determinants of health (SDoH), including race and economic status, and inflammatory response and outcomes in myocarditis. The result is a proposal for the reclassification of myocarditis that integrates the latest knowledge of immunological pathogenesis to refine estimates of prognosis and target pathway-specific treatments

Demographic and indication-specific characteristics have limited association with social network engagement: evidence from 24,954 members of four health care support groups

Background: Digital health social networks (DHSNs) are widespread, and the consensus is that they contribute to wellness by offering social support and knowledge sharing. The success of a DHSN is based on the number of participants and their consistent creation of externalities through the generation of new content. To promote network growth, it would be helpful to identify characteristics of superusers or actors who create value by generating positive network externalities. Objective: The aim of the study was to investigate the feasibility of developing predictive models that identify potential superusers in real time. This study examined associations between posting behavior, 4 demographic variables, and 20 indication-specific variables. Methods: Data were extracted from the custom structured query language (SQL) databases of 4 digital health behavior change interventions with DHSNs. Of these, 2 were designed to assist in the treatment of addictions (problem drinking and smoking cessation), and 2 for mental health (depressive disorder, panic disorder). To analyze posting behavior, 10 models were developed, and negative binomial regressions were conducted to examine associations between number of posts, and demographic and indication-specific variables. Results: The DHSNs varied in number of days active (3658-5210), number of registrants (5049-52,396), number of actors (1085-8452), and number of posts (16,231-521,997). In the sample, all 10 models had low R2 values (.013-.086) with limited statistically significant demographic and indication-specific variables. Conclusions: Very few variables were associated with social network engagement. Although some variables were statistically significant, they did not appear to be practically significant. Based on the large number of study participants, variation in DHSN theme, and extensive time-period, we did not find strong evidence that demographic characteristics or indication severity sufficiently explain the variability in number of posts per actor. Researchers should investigate alternative models that identify superusers or other individuals who create social network externalities

ABCB1 (MDR1) polymorphisms and ovarian cancer progression and survival: A comprehensive analysis from the Ovarian Cancer Association Consortium and The Cancer Genome Atlas

<b>Objective</b> <i>ABCB1</i> encodes the multi-drug efflux pump P-glycoprotein (P-gp) and has been implicated in multi-drug resistance. We comprehensively evaluated this gene and flanking regions for an association with clinical outcome in epithelial ovarian cancer (EOC).<p></p> <b>Methods</b> The best candidates from fine-mapping analysis of 21 <i>ABCB1</i> SNPs tagging C1236T (rs1128503), G2677T/A (rs2032582), and C3435T (rs1045642) were analysed in 4616 European invasive EOC patients from thirteen Ovarian Cancer Association Consortium (OCAC) studies and The Cancer Genome Atlas (TCGA). Additionally we analysed 1,562 imputed SNPs around ABCB1 in patients receiving cytoreductive surgery and either ‘standard’ first-line paclitaxel–carboplatin chemotherapy (n = 1158) or any first-line chemotherapy regimen (n = 2867). We also evaluated ABCB1 expression in primary tumours from 143 EOC patients.<p></p> <b>Result</b> Fine-mapping revealed that rs1128503, rs2032582, and rs1045642 were the best candidates in optimally debulked patients. However, we observed no significant association between any SNP and either progression-free survival or overall survival in analysis of data from 14 studies. There was a marginal association between rs1128503 and overall survival in patients with nil residual disease (HR 0.88, 95% CI 0.77–1.01; p = 0.07). In contrast, <i>ABCB1</i> expression in the primary tumour may confer worse prognosis in patients with sub-optimally debulked tumours.<p></p> <b>Conclusion</b> Our study represents the largest analysis of <i>ABCB1</i> SNPs and EOC progression and survival to date, but has not identified additional signals, or validated reported associations with progression-free survival for rs1128503, rs2032582, and rs1045642. However, we cannot rule out the possibility of a subtle effect of rs1128503, or other SNPs linked to it, on overall survival.<p></p&gt

The necessities and luxuries of mate preferences: Testing the tradeoffs

Social exchange and evolutionary models of mate selection incorporate economic assumptions but have not considered a key distinction between necessities and luxuries. This distinction can clarify an apparent paradox: Status and attractiveness, though emphasized by many researchers, are not typically rated highly by research participants. Three studies supported the hypothesis that women and men first ensure sufficient levels of necessities in potential mates before considering many other characteristics rated as more important in prior surveys. In Studies 1 and 2, participants designed ideal long-term mates, purchasing various characteristics with 3 different budgets. Study 3 used a mate-screening paradigm and showed that people inquire 1st about hypothesized necessities. Physical attractiveness was a necessity to men, status and resources were necessities to women, and kindness and intelligence were necessities to both. Relationship researchers adopting social exchange and evolutionary perspectives have used economic principles (e.g., Hatfield, Utne, & Traupmann, 1979; Kenrick, Groth, Trost, & Sadalla, 1993). However, a key distinction from economics has been omitted—necessities versus luxuries (e.g., Varian, 1984). Though peopl