Topological Speed Limits to Network Synchronization

We study collective synchronization of pulse-coupled oscillators interacting on asymmetric random networks. We demonstrate that random matrix theory can be used to accurately predict the speed of synchronization in such networks in dependence on the dynamical and network parameters. Furthermore, we show that the speed of synchronization is limited by the network connectivity and stays finite, even if the coupling strength becomes infinite. In addition, our results indicate that synchrony is robust under structural perturbations of the network dynamics.Comment: 5 pages, 3 figure

Leibniz Seminorms and Best Approximation from C*-subalgebras

We show that if B is a C*-subalgebra of a C*-algebra A such that B contains a bounded approximate identity for A, and if L is the pull-back to A of the quotient norm on A/B, then L is strongly Leibniz. In connection with this situation we study certain aspects of best approximation of elements of a unital C*-algebra by elements of a unital C*-subalgebra.Comment: 24 pages. Intended for the proceedings of the conference "Operator Algebras and Related Topics". v2: added a corollary to the main theorem, plus several minor improvements v3: much simplified proof of a key lemma, corollary to main theorem added v4: Many minor improvements. Section numbers increased by

Multiple parasite infections and their relationship to self-reported morbidity in a community of rural Côte d'Ivoire

Background Concomitant parasitic infections are common in the developing world, yet most studies focus on a single parasite in a narrow age group. We investigated the extent of polyparasitism and parasite associations, and related these findings to self-reported morbidity. Methods Inhabitants of 75 randomly selected households from a single village in western Côte d'Ivoire provided multiple faecal specimens and a single finger prick blood sample. The Kato-Katz technique and a formol-ether concentration method were employed to screen faecal samples for Schistosoma mansoni, soil-transmitted helminths and intestinal protozoa. Giemsa-stained blood smears were analysed for malaria parasites. A questionnaire was administered for collection of demographic information and self-reported morbidity indicators. Results Complete parasitological data were obtained for 500/561 (89.1%) participants, similarly distributed among sex, with an age range from 5 days to 91 years. The prevalences of Plasmodium falciparum, hookworms, Entamoeba histolytica/E. dispar, and S. mansoni were 76.4%, 45.0%, 42.2%, and 39.8%, respectively. Three-quarters of the population harboured three or more parasites concurrently. Multivariate analysis revealed significant associations between several pairs of parasites. Some parasitic infections and the total number of parasites were significantly associated with self-reported morbidity indicators. Conclusions Our data confirm that polyparasitism is very common in rural Côte d'Ivoire and that people have clear perceptions about the morbidity caused by some of these parasitic infections. Our findings can be used for the design and implementation of sound intervention strategies to mitigate morbidity and co-morbidit

Tissue Microenvironments Define and Get Reinforced by Macrophage Phenotypes in Homeostasis or during Inflammation, Repair and Fibrosis

Current macrophage phenotype classifications are based on distinct in vitro culture conditions that do not adequately mirror complex tissue environments. In vivo monocyte progenitors populate all tissues for immune surveillance which supports the maintenance of homeostasis as well as regaining homeostasis after injury. Here we propose to classify macrophage phenotypes according to prototypical tissue environments, e.g. as they occur during homeostasis as well as during the different phases of (dermal) wound healing. In tissue necrosis and/or infection, damage- and/or pathogen-associated molecular patterns induce proinflammatory macrophages by Toll-like receptors or inflammasomes. Such classically activated macrophages contribute to further tissue inflammation and damage. Apoptotic cells and antiinflammatory cytokines dominate in postinflammatory tissues which induce macrophages to produce more antiinflammatory mediators. Similarly, tumor-associated macrophages also confer immunosuppression in tumor stroma. Insufficient parenchymal healing despite abundant growth factors pushes macrophages to gain a profibrotic phenotype and promote fibrocyte recruitment which both enforce tissue scarring. Ischemic scars are largely devoid of cytokines and growth factors so that fibrolytic macrophages that predominantly secrete proteases digest the excess extracellular matrix. Together, macrophages stabilize their surrounding tissue microenvironments by adapting different phenotypes as feed-forward mechanisms to maintain tissue homeostasis or regain it following injury. Furthermore, macrophage heterogeneity in healthy or injured tissues mirrors spatial and temporal differences in microenvironments during the various stages of tissue injury and repair. Copyright (C) 2012 S. Karger AG, Base

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers

Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 x 10(53)). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 x 10(-20)). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management

A statistical review of light curves and the prevalence of contact binaries in the Kuiper Belt

We investigate what can be learned about a population of distant Kuiper Belt Objects (KBOs) by studying the statistical properties of their light curves. Whereas others have successfully inferred the properties of individual, highly variable KBOs, we show that the fraction of KBOs with low amplitudes also provides fundamental information about a population. Each light curve is primarily the result of two factors: shape and orientation. We consider contact binaries and ellipsoidal shapes, with and without flattening. After developing the mathematical framework, we apply it to the existing body of KBO light curve data. Principal conclusions are as follows. (1) When using absolute magnitude H as a proxy for the sizes of KBOs, it is more accurate to use the maximum of the light curve (minimum H) rather than the mean. (2) Previous investigators have noted that smaller KBOs tend to have higher-amplitude light curves, and have interpreted this as evidence that they are systematically more irregular in shape than larger KBOs; we show that a population of flattened bodies with uniform proportions, independent of size, could also explain this result. (3) Our method of analysis indicates that prior assessments of the fraction of contact binaries in the Kuiper Belt may be artificially low. (4) The pole orientations of some KBOs can be inferred from observed changes in their light curves over time scales of decades; however, we show that these KBOs constitute a biased sample, whose pole orientations are not representative of the population overall. (5) Although surface topography, albedo patterns, limb darkening, and other surface properties can affect individual light curves, they do not have a strong influence on the statistics overall. (6) Photometry from the Outer Solar System Origins Survey (OSSOS) survey is incompatible with previous results and its statistical properties defy easy interpretation. We also discuss the promise of this approach for the analysis of future, much larger data sets such as the one anticipated from the upcoming Vera C. Rubin Observatory