Tissue biomarkers of breast cancer and their association with conventional pathologic features

Background:Tissue protein expression profiling has the potential to detect new biomarkers to improve breast cancer (BC) diagnosis, staging, and prognostication. This study aimed to identify tissue proteins that differentiate breast cancer tissue from healthy breast tissue using protein chip mass spectrometry and to examine associations with conventional pathological features.Methods:To develop a training model, 82 BC and 82 adjacent unaffected tissue (AT) samples were analysed on cation-exchange protein chips by time-of-flight mass spectrometry. For validation, 89 independent BC and AT sample pairs were analysed.Results:From the protein peaks that were differentially expressed between BC and AT by univariate analysis, binary logistic regression yielded two peaks that together classified BC and AT with a ROC area under the curve of 0.92. Two proteins, ubiquitin and S100P (in a novel truncated form), were identified by liquid chromatography/tandem mass spectrometry and validated by immunoblotting and reactive-surface protein chip immunocapture. The combined marker panel was positively associated with high histologic grade, larger tumour size, lymphovascular invasion, ER and PR positivity, and HER2 overexpression, suggesting that it may be associated with a HER2-enriched molecular subtype of breast cancer.Conclusion:This independently validated protein panel may be valuable in the classification and prognostication of breast cancer patients. © 2013 Cancer Research UK. All rights reserved

The Routing of Complex Contagion in Kleinberg's Small-World Networks

In Kleinberg's small-world network model, strong ties are modeled as deterministic edges in the underlying base grid and weak ties are modeled as random edges connecting remote nodes. The probability of connecting a node $u$ with node $v$ through a weak tie is proportional to $1/|uv|^\alpha$, where $|uv|$ is the grid distance between $u$ and $v$ and $\alpha\ge 0$ is the parameter of the model. Complex contagion refers to the propagation mechanism in a network where each node is activated only after $k \ge 2$ neighbors of the node are activated. In this paper, we propose the concept of routing of complex contagion (or complex routing), where we can activate one node at one time step with the goal of activating the targeted node in the end. We consider decentralized routing scheme where only the weak ties from the activated nodes are revealed. We study the routing time of complex contagion and compare the result with simple routing and complex diffusion (the diffusion of complex contagion, where all nodes that could be activated are activated immediately in the same step with the goal of activating all nodes in the end). We show that for decentralized complex routing, the routing time is lower bounded by a polynomial in $n$ (the number of nodes in the network) for all range of $\alpha$ both in expectation and with high probability (in particular, $\Omega(n^{\frac{1}{\alpha+2}})$ for $\alpha \le 2$ and $\Omega(n^{\frac{\alpha}{2(\alpha+2)}})$ for $\alpha > 2$ in expectation), while the routing time of simple contagion has polylogarithmic upper bound when $\alpha = 2$. Our results indicate that complex routing is harder than complex diffusion and the routing time of complex contagion differs exponentially compared to simple contagion at sweetspot.Comment: Conference version will appear in COCOON 201

Measurement of charge and light yields for Xe 127 L -shell electron captures in liquid xenon

Dark matter searches using dual-phase xenon time-projection chambers (LXe-TPCs) rely on their ability to reject background electron recoils (ERs) while searching for signal-like nuclear recoils (NRs). ER response is typically calibrated using β-decay sources, such as tritium, but these calibrations do not characterize events accompanied by an atomic vacancy, as in solar neutrino scatters off inner-shell electrons. Such events lead to emission of x rays and Auger electrons, resulting in higher electron-ion recombination and thus a more NR-like response than inferred from β-decay calibration. We present a cross-calibration of tritium β-decays and Xe127 electron-capture decays (which produce inner-shell vacancies) in a small-scale LXe-TPC and give the most precise measurements to date of light and charge yields for the Xe127 L-shell electron-capture in liquid xenon. We observe a 6.9σ (9.2σ) discrepancy in the L-shell capture response relative to tritium β decays, measured at a drift field of 363±14 V/cm (258±13 V/cm), when compared to simulations tuned to reproduce the correct β-decay response. In dark matter searches, use of a background model that neglects this effect leads to overcoverage (higher limits) for background-only multi-kiloton-year exposures, but at a level much less than the 1-σ experiment-to-experiment variation of the 90% C.L. upper limit on the interaction rate of a 50 GeV/c2 dark matter particle

Plantar fasciitis and calcaneal spur formation are associated with abductor digiti minimi atrophy on MRI of the foot

Objective To determine the association of atrophy of the abductor digiti minimi muscle (ADMA), an MRI manifestation of chronic compression of the inferior calcaneal nerve suggesting the clinical diagnosis of Baxter’s neuropathy, with MRI markers of potential etiologies, including calcaneal spur formation, plantar fasciitis, calcaneal edema, Achilles tendinosis and posterior tibial tendon dysfunction (PTTD). Materials and methods Prevalence of calcaneal spur formation, plantar fasciitis, calcaneal edema, Achilles tendinosis and PTTD was assessed retrospectively on 100 MRI studies with ADMA and 100 MRI studies without ADMA. Patients ranged in age from 10–92 years. Pearson chi-square analyses and Fisher’s exact test were used to compare prevalence of the above findings in patients with and without ADMA. Logistic regression was used to determine which variables were significantly associated with ADMA. Results Among patients with ADMA, there was significantly greater age (57.2 years vs 40.8 years, p \u3c 0.001), presence of Achilles tendinosis (22.0% vs 3.0%, P \u3c 0.001), calcaneal edema (15.0% vs 3.0%, P = 0.005), calcaneal spur (48.0% vs 7.0%, P \u3c 0.001), plantar fasciitis (52.5% vs 11.0%, P \u3c 0.001), and PTTD (32.0% vs 11.0%, P \u3c 0.001). After multivariate logistic regression analysis, only age [odds ratio (OR) 1.06, 95% confidence interval (CI) 1.03, 1.09], calcaneal spur (OR 3.60, 95% CI 1.28, 10.17), and plantar fasciitis (OR 3.35, 95% CI 1.31, 8.56) remained significant. Conclusion Advancing age, calcaneal spur, and plantar fasciitis are significantly associated with ADMA. Their high odds ratios support the notion of a possible etiologic role for calcaneal spur and plantar fasciitis in the progression to Baxter’s neuropathy

Bulk Segregant Analysis Using Single Nucleotide Polymorphism Microarrays

Bulk segregant analysis (BSA) using microarrays, and extreme array mapping (XAM) have recently been used to rapidly identify genomic regions associated with phenotypes in multiple species. These experiments, however, require the identification of single feature polymorphisms (SFP) between the cross parents for each new combination of genotypes, which raises the cost of experiments. The availability of the genomic polymorphism data in Arabidopsis thaliana, coupled with the efficient designs of Single Nucleotide Polymorphism (SNP) genotyping arrays removes the requirement for SFP detection and lowers the per array cost, thereby lowering the overall cost per experiment. To demonstrate that these approaches would be functional on SNP arrays and determine confidence intervals, we analyzed hybridizations of natural accessions to the Arabidopsis ATSNPTILE array and simulated BSA or XAM given a variety of gene models, populations, and bulk selection parameters. Our results show a striking degree of correlation between the genotyping output of both methods, which suggests that the benefit of SFP genotyping in context of BSA can be had with the cheaper, more efficient SNP arrays. As a final proof of concept, we hybridized the DNA from bulks of an F2 mapping population of a Sulfur and Selenium ionomics mutant to both the Arabidopsis ATTILE1R and ATSNPTILE arrays, which produced almost identical results. We have produced R scripts that prompt the user for the required parameters and perform the BSA analysis using the ATSNPTILE1 array and have provided them as supplemental data files

Impact of socioeconomic deprivation on rate and cause of death in severe mental illness

Background: Socioeconomic status has important associations with disease-specific mortality in the general population. Although individuals with Severe Mental Illnesses (SMI) experience significant premature mortality, the relationship between socioeconomic status and mortality in this group remains under investigated.<p></p> Aims: To assess the impact of socioeconomic status on rate and cause of death in individuals with SMI (schizophrenia and bipolar disorder) relative to the local (Glasgow) and wider (Scottish) populations.<p></p> Methods: Cause and age of death during 2006-2010 inclusive for individuals with schizophrenia or bipolar disorder registered on the Glasgow Psychosis Clinical Information System (PsyCIS) were obtained by linkage to the Scottish General Register Office (GRO). Rate and cause of death by socioeconomic status, measured by Scottish Index of Multiple Deprivation (SIMD), were compared to the Glasgow and Scottish populations.<p></p> Results: Death rates were higher in people with SMI across all socioeconomic quintiles compared to the Glasgow and Scottish populations, and persisted when suicide was excluded. Differences were largest in the most deprived quintile (794.6 per 10,000 population vs. 274.7 and 252.4 for Glasgow and Scotland respectively). Cause of death varied by socioeconomic status. For those living in the most deprived quintile, higher drug-related deaths occurred in those with SMI compared to local Glasgow and wider Scottish population rates (12.3% vs. 5.9%, p = <0.001 and 5.1% p = 0.002 respectively). A lower proportion of deaths due to cancer in those with SMI living in the most deprived quintile were also observed, relative to the local Glasgow and wider Scottish populations (12.3% vs. 25.1% p = 0.013 and 26.3% p = <0.001). The proportion of suicides was significantly higher in those with SMI living in the more affluent quintiles relative to Glasgow and Scotland (54.6% vs. 5.8%, p = <0.001 and 5.5%, p = <0.001). Discussion and conclusions: Excess mortality in those with SMI occurred across all socioeconomic quintiles compared to the Glasgow and Scottish populations but was most marked in the most deprived quintiles when suicide was excluded as a cause of death. Further work assessing the impact of socioeconomic status on specific causes of premature mortality in SMI is needed