Small world in the real world: Long distance dispersal governs epidemic dynamics in agricultural landscapes

Outbreaks of a plant disease in a landscape can be meaningfully modelled using networks with nodes representing individual crop-fields, and edges representing potential infection pathways between them. Their spatial structure, which resembles that of a regular lattice, makes such networks fairly robust against epidemics. Yet, it is well-known how the addition of a few shortcuts can turn robust regular lattices into vulnerable ‘small world’ networks. Although the relevance of this phenomenon has been shown theoretically for networks with nodes corresponding to individual host plants, its real-world implications at a larger scale (i.e. in networks with nodes representing crop fields or other plantations) remain elusive. Focusing on realistic spatial networks connecting olive orchards in Andalusia (Southern Spain), the world’s leading olive producer, we show how even very small probabilities of long distance dispersal of infectious vectors result in a small-world effect that dramatically exacerbates a hypothetical outbreak of a disease targeting olive trees (loosely modelled on known epidemiological information on the bacterium Xylella fastidiosa, an important emerging threat for European agriculture). More specifically, we found that the probability of long distance vector dispersal has a disproportionately larger effect on epidemic dynamics compared to pathogen’s intrinsic infectivity, increasing total infected area by up to one order of magnitude (in the absence of quarantine). Furthermore, even a very small probability of long distance dispersal increased the effort needed to halt a hypothetical outbreak through quarantine by about 50% in respect to scenarios modelling local/short distance pathogen’s dispersal only. This highlights how identifying (and disrupting) long distance dispersal processes may be more efficacious to contain a plant disease epidemic than surveillance and intervention concentrated on local scale transmission processes.Peer reviewe

Determination of regional coronary flow utilizing microspheres in ex vivo myocardial ischemia/reperfusion (MI/R) injury

MI/R results in marked cardiac contractile dysfunction and cell death. We previously discovered that protein kinase C epsilon peptide inhibitor (PKC ε-) robustly restored post-reperfused cardiac function, and reduced infarct size, oxidative stress, and leukocyte endothelial interactions in coronary, hind limb, renal, and mesenteric vascular inflammation models. The mechanisms of these effects in part are due to attenuating uncoupled endothelial nitric oxide (NO) synthase activity and increase endothelial NO bioavailability. Therefore, we hypothesize that PKC ε- will increase regional flow during reperfusion. We determined regional flow to the right ventricle, left ventricle, and septum at baseline and after 10 and 45 min reperfusion using fluorescent microspheres in isolated rat perfused hearts subjected to global I(30min)/R(45min). A cell permeable PKC ε- (myr-EAVSLKPT, MW=1054 g/mol, 10μM, n=8) was given at beginning of reperfusion for 5 min. We found that final left ventricular developed pressure (LVDP) recovered to 70 ± 7%, maximal rate of left ventricular contraction, +dP/dtmax to 57 ± 7% and maximal rate of left ventricular relaxation, -dP/dtmin to 58 ± 6% of baseline values. These parameters were significantly improved compared to untreated I/R hearts (n=7) that only recovered to 30 ± 5% in LVDP, 21 ± 5% in dP/dtmax and 25 ± 5% in dP/dtmin relative to baseline values (all p \u3c 0.01). Moreover, our preliminary data suggest that PKC ε- treatment increased regional flow by 190 ± 40% in the right ventricle, 140 ± 30% in the left ventricle, and 120 ± 20% in the septum at 10 min. post reperfusion compared to non-treated control MI/R hearts. These values were maintained throughout the remaining 35 min of reperfusion. In summary, the data indicates that PKC ε- improves postreperfused cardiac function in part by restoration of regional flow

Linking parasitism to network centrality and the impact of sampling bias in its interpretation

Group living is beneficial for individuals, but also comes with costs. One such cost is the increased possibility of pathogen transmission because increased numbers or frequencies of social contacts are often associated with increased parasite abundance or diversity. The social structure of a group or population is paramount to patterns of infection and transmission. Yet, for various reasons, studies investigating the links between sociality and parasitism in animals, especially in primates, have only accounted for parts of the group (e.g., only adults), which is likely to impact the interpretation of results. Here, we investigated the relationship between social network centrality and an estimate of gastrointestinal helminth infection intensity in a whole group of Japanese macaques (Macaca fuscata). We then tested the impact of omitting parts of the group on this relationship. We aimed to test: (1) whether social network centrality –in terms of the number of partners (degree), frequency of interactions (strength), and level of social integration (eigenvector) –was linked to parasite infection intensity (estimated by eggs per gram of faeces, EPG); and, (2) to what extent excluding portions of individuals within the group might influence the observed relationship. We conducted social network analysis on data collected from one group of Japanese macaques over three months on Koshima Island, Japan. We then ran a series of knock-out simulations. General linear mixed models showed that, at the whole-group level, network centrality was positively associated with geohelminth infection intensity. However, in partial networks with only adult females, only juveniles, or random subsets of the group, the strength of this relationship - albeit still generally positive - lost statistical significance. Furthermore, knock-out simulations where individuals were removed but network metrics were retained from the original whole-group network showed that these changes are partly a power issue and partly an effect of sampling the incomplete network. Our study indicates that sampling bias can thus hamper our ability to detect real network effects involving social interaction and parasitism. In addition to supporting earlier results linking geohelminth infection to Japanese macaque social networks, this work introduces important methodological considerations for research into the dynamics of social transmission, with implications for infectious disease epidemiology, population management, and health interventions

The cardioprotective effects of caffeic acid phenethyl ester (CAPE) on myocardial ischemia/reperfusion (I/R) injury

Oxidative stress plays a major role in causing reperfusion injury following prolonged ischemia. CAPE has been shown to have antioxidant, anti-inflammatory, and cardioprotective effects following regional myocardial ischemia/reperfusion injury. The effects and mechanisms of CAPE in global myocardial I/R injury are still unclear. In this study, CAPE was tested in isolated perfused rat hearts following global I (30 min)/R (60 min). We recorded left ventricular developed pressure (LVDP), left ventricular end systolic pressure (LVESP), the peak of the first derivative of left ventricular pressure (dP/dtmax), and infarct size. We found that untreated I/R hearts (n=11) recovered LVDP to 45 ± 8% (p\u3c0.05), LVESP to 106 ± 7% (p\u3c0.05), and dP/dtmax to 33 ± 5% (p\u3c0.05) of baseline values, respectively, at the end of 60 minutes reperfusion. By contrast, CAPE (40 mM, n=6) given at reperfusion for 5 minutes significantly restored LVDP to 75 ± 15%, LVESP to 133 ± 13%, and dP/dtmax to 54 ± 12% of baseline values, respectively (all p\u3c0.05). Moreover, CAPE also significantly reduced infarct size to 19 ± 2% (n=6) compared t

The Effect of Caffeic Acid Phenethyl Ester (CAPE) on H2O2-Induced Oxidative Stress in Cultured H9c2 Cells Compared to Common Antioxidants

Caffeic Acid Phenethyl Ester (CAPE) is a natural compound that has previously exhibited anti-proliferative, anti-inflammation and antioxidant activities. However, CAPE’s effects have not been fully elucidated in myoblasts under oxidative stress. We compared the effects of 24 hour pretreatment of CAPE to several known antioxidants (caffeic acid, vitamin C, and trolox) in H9c2 cells following oxidative injury by hydrogen peroxide (H2O2). H9c2 cells incubated with H2O2 treatment (100-700 μM, n=4) for 24 hours dose-dependently reduced cell viability (assessed by a cell counting assay). Compared to the reduction in viability from H2O2 500 μM treatment (22 ± 4%), H9c2 cell viability was significantly restored by pretreatment of CAPE (at 10 μM (100 ± 25%); 20 μM (112 ± 15%); 40 μM (109 ± 15%) n=5, p\u3c0.001) and Trolox (at 50 μM (83 ± 10%); 100 μM (89 ± 8%) n=4, p\u3c0.001). In contrast, pretreatment of H9c2 cells with caffeic acid (1-80 μM, n=3) and vitamin C (1000-10,000 μM, n=3) did not restore cell viability following H2O2-induced injury. CAPE’s mechanism was further investigated by measuring reactive oxygen species via a dichlorofluorescin diacetate assay and by evaluating heme oxygenase-1 (HO-1) expression via western blot. Increases in ROS caused by H2O2 500 μM (239 ± 30% of control, n=3) were significantly restored to control by pretreatment of CAPE dose-dependently (n=3, p\u3c0.001). Moreover, CAPE dose-dependently increased HO-1 expression (n=3). These results suggest CAPE can mitigate oxidative stress in H9c2 cells which may involve the induction of HO-1

The Effects of Caffeic Acid Phenethyl Ester (Cape) on Oxidative Stress and Hypoxia

Oxidative stress has been implicated in pathogenesis of hypoxia and ischemia/reperfusion (I/R) injury. In previous studies, we have shown that the antioxidant CAPE exerted cardioprotection in an isolated rat heart I (30 min)/R (60 min) injury model. In this study, we further evaluated the effects of CAPE on oxidative stress and hypoxia-induced cell damage. We evaluated the inhibition of absorbance in the phorbol 12-myristate 13-acetate (30 nM) induced superoxide production spectrophotometrically in isolated rat neutrophils via reduction of exogenous cytochrome C. We found that CAPE (0.5 µM- 40 µM; n=4-13) reduced phorbol 12-myristate 13-acetate induced neutrophil superoxide release dose-dependently from 29±3% to 95±2%. In a rat hind limb I (30 min)/R (60 min) model, blood hydrogen peroxide levels serves as an indicator of blood oxidative stress and was measured in real-time via a hydrogen peroxide microsensor (100 μm) inserted into both femoral veins (one served as sham, the other as I/R). We found that in the control group, I/R significantly increased blood hydrogen peroxide levels to 2.1±0.8 μM relative to the sham limb at 60 minutes reperfusion when saline was given at the beginning of reperfusion (n=5). By contrast, CAPE when given at reperfusion (40 µM, n=5) significantly reduced blood hydrogen peroxide levels from 30 min reperfusion and throughout the rest of experiment (p This study was supported by Division of Research and Department of Bio-Medical Sciences at Philadelphia College of Osteopathic Medicine

Toxicity and Surgical Complication Rates of Neoadjuvant Atezolizumab in Patients with Muscle-invasive Bladder Cancer Undergoing Radical Cystectomy: Updated Safety Results from the ABACUS Trial

[Background] There are limited data on toxicity and surgical safety associated with neoadjuvant programmed death ligand 1 (PD-L1) inhibitors prior to radical cystectomy (RC) in patients with muscle-invasive bladder cancer (MIBC).[Objective] To present a comprehensive safety analysis of the largest neoadjuvant series, with focus on timing and severity of toxicity and surgical complications occurring after neoadjuvant atezolizumab in patients with MIBC enrolled in the ABACUS trial.[Design, setting, and participants] ABACUS (NCT02662309) is an open-label, multicenter, phase II trial for patients with histologically confirmed (T2-T4aN0M0) MIBC, awaiting RC. Patients either were ineligible or refused cisplatin-based neoadjuvant chemotherapy.[Intervention] Two cycles of neoadjuvant atezolizumab (1200 mg, every 3 wk) followed by RC.[Outcome measurements and statistical analysis] Description of atezolizumab toxicity profile in the neoadjuvant setting, impact on surgery, and delayed immune-mediated adverse events (AEs) were assessed.[Results and limitations] Ninety-five patients received treatment. Of them, 44% (42/95) had atezolizumab-related AEs during the neoadjuvant period (fatigue [20%], decreased appetite [6%], and transaminases increased [6%]). Treatment-related grade 3–5 AEs occurred in 11% (10/95) of patients during the study. Of the patients, 21% (20/95) received only one cycle of atezolizumab due to AEs; 92% (87/95) underwent RC. No surgery was delayed due to atezolizumab-related toxicities. Surgical complications occurred in 62% (54/87) of patients. Of these patients, 43% (37/87) and 20% (17/87) had minor (grade 1–2) and major (grade 3–5) complications, respectively. Thirteen of 87 (15%) patients had post-RC atezolizumab-related AEs, including adrenal insufficiency and transaminases increased. Three deaths occurred during the period of study-related interventions (one non–treatment-related aspiration pneumonia, one immune-related myocardial infarction, and one cardiogenic shock after RC). Not all surgical safety parameters were available.[Conclusions] Two cycles of neoadjuvant atezolizumab are well tolerated and do not seem to impact surgical complication rates. Owing to the long half-life, AEs may occur in the postoperative period, including endocrine abnormalities requiring attention and intervention.[Patient summary] Here, we report a comprehensive dataset of patients receiving neoadjuvant immune checkpoint inhibitors before radical cystectomy. Treatment with neoadjuvant atezolizumab is safe and does not seem to complicate surgery significantly.Queen Mary University of London was the Sponsor of the study. Roche granted QMUL funding for the study. J. Bull and M. Jacobson also provided financial support for aspects of the biomarker analysis. We acknowledge Cancer Research UK, the UK Experimental Cancer Medicine Network, and La Roche-Hoffmann for funding.Peer reviewe

A Search for the Transit of HD 168443b: Improved Orbital Parameters and Photometry

The discovery of transiting planets around bright stars holds the potential to greatly enhance our understanding of planetary atmospheres. In this work we present the search for transits of HD 168443b, a massive planet orbiting the bright star HD 168443 V=6.92 with a period of 58.11 days. The high eccentricity of the planetary orbit e=0.53 significantly enhances the a-priori transit probability beyond that expected for a circular orbit, making HD 168443 a candidate for our ongoing Transit Ephemeris Refinement and Monitoring Survey (TERMS). Using additional radial velocities from Keck-HIRES, we refined the orbital parameters of this multi-planet system and derived a new transit ephemeris for HD 168443b. The reduced uncertainties in the transit window make a photometric transit search practicable. Photometric observations acquired during predicted transit windows were obtained on three nights. CTIO 1.0 m photometry acquired on 2010 September 7 had the required precision to detect a transit but fell just outside of our final transit window. Nightly photometry from the T8 0.8 m Automated Photometric Telescope (APT) at Fairborn Observatory, acquired over a span of 109 nights, demonstrates that HD 168443 is constant on a time scale of weeks. Higher-cadence photometry on 2011 April 28 and June 25 shows no evidence of a transit. We are able to rule out a non-grazing transit of HD 168443b.Comment: Accepted in ApJ. 25 pages. 8 Figure

Multi-spectral terahertz sensing: proposal for a coupled-cavity quantum cascade laser based optical feedback interferometer

We propose a laser feedback interferometer operating at multiple terahertz (THz) frequency bands by using a pulsed coupled-cavity THz quantum cascade laser (QCL) under optical feedback. A theoretical model that contains multi-mode reduced rate equations and thermal equations is presented, which captures the interplay between electro-optical, thermal, and feedback effects. By using the self-heating effect in both active and passive cavities, self-mixing signal responses at three different THz frequency bands are predicted. A multi-spectral laser feedback interferometry system based on such a coupled-cavity THz QCL will permit ultra-high-speed sensing and spectroscopic applications including material identification