1,076 research outputs found
Inertia based microfluidic capture and characterisation of circulating tumour cells for the diagnosis of lung cancer
Background: Routine clinical application of circulating tumour cells (CTCs) for blood based diagnostics is yet to be established. Despite growing evidence of their clinical utility for diagnosis, prognosis and treatment monitoring, the efficacy of a robust platform and universally accepted diagnostic criteria remain uncertain. We evaluate the diagnostic performance of a microfluidic CTC isolation platform using cytomorphologic criteria in patients undergoing lung cancer surgery.
Methods: Blood was processed from 51 patients undergoing surgery for known or suspected lung cancer using the ClearBridge ClearCell FX systemTM (ClearBridge Biomedics, Singapore). Captured cells were stained on slides with haematoxylin and eosin (H&E) and independently assessed by two pathologist teams. Diagnostic performance was evaluated against the pathologists reported diagnosis of cancer from surgically obtained specimens. Results: Cancer was diagnosed in 43.1% and 54.9% of all cases. In early stage primary lung cancer, between the two reporting teams, a positive diagnosis of CTCs was made for 50% and 66.7% of patients. The agreement between the reporting teams was 80.4%, corresponding to a kappa-statistic of 0.61±0.11 (P<0.001), indicating substantial agreement. Sensitivity levels for the two teams were calculated as 59% (95% CI, 41–76%) and 41% (95% CI, 24–59%), with a specificity of 53% for both.
Conclusions: The performance of the tested microfluidic antibody independent device to capture CTCs using standard cytomorphological criteria provides the potential of a diagnostic blood test for lung cancer
Cholesterol and the risk of grade-specific prostate cancer incidence: evidence from two large prospective cohort studies with up to 37 years' follow up
<b>Background</b>
High cholesterol may be a modifiable risk factor for prostate cancer but results have been inconsistent and subject to potential "reverse causality" where undetected disease modifies cholesterol prior to diagnosis.<p></p>
<b>Methods</b>
We conducted a prospective cohort study of 12,926 men who were enrolled in the Midspan studies between 1970 and 1976 and followed up to 31st December 2007. We used Cox-Proportional Hazards Models to evaluate the association between baseline plasma cholesterol and Gleason grade-specific prostate cancer incidence. We excluded cancers detected within at least 5 years of cholesterol assay.<p></p>
<b>Results</b>
650 men developed prostate cancer in up to 37 years' follow-up. Baseline plasma cholesterol was positively associated with hazard of high grade (Gleason score[greater than or equal to]8) prostate cancer incidence (n=119). The association was greatest among men in the 4th highest quintile for cholesterol, 6.1 to <6.69 mmol/l, Hazard Ratio 2.28, 95% CI 1.27 to 4.10, compared with the baseline of <5.05 mmol/l. This association remained significant after adjustment for body mass index, smoking and socioeconomic status.<p></p>
<b>Conclusions</b>
Men with higher cholesterol are at greater risk of developing high-grade prostate cancer but not overall risk of prostate cancer. Interventions to minimise metabolic risk factors may have a role in reducing incidence of aggressive prostate cancer
Targeted knock-down of miR21 primary transcripts using snoMEN vectors induces apoptosis in human cancer cell lines
We have previously reported an antisense technology, 'snoMEN vectors', for targeted knock-down of protein coding mRNAs using human snoRNAs manipulated to contain short regions of sequence complementarity with the mRNA target. Here we characterise the use of snoMEN vectors to target the knock-down of micro RNA primary transcripts. We document the specific knock-down of miR21 in HeLa cells using plasmid vectors expressing miR21-targeted snoMEN RNAs and show this induces apoptosis. Knock-down is dependent on the presence of complementary sequences in the snoMEN vector and the induction of apoptosis can be suppressed by over-expression of miR21. Furthermore, we have also developed lentiviral vectors for delivery of snoMEN RNAs and show this increases the efficiency of vector transduction in many human cell lines that are difficult to transfect with plasmid vectors. Transduction of lentiviral vectors expressing snoMEN targeted to pri-miR21 induces apoptosis in human lung adenocarcinoma cells, which express high levels of miR21, but not in human primary cells. We show that snoMEN-mediated suppression of miRNA expression is prevented by siRNA knock-down of Ago2, but not by knock-down of Ago1 or Upf1. snoMEN RNAs colocalise with Ago2 in cell nuclei and nucleoli and can be co-immunoprecipitated from nuclear extracts by antibodies specific for Ago2
Stage-Specific Effects of Population Density on the Development and Fertility of the Western Tarnished Plant Bug, Lygus hesperus
The western tarnished plant bug Lygus hesperus Knight (Heteroptera: Miridae), a major pest of cotton and other key economic crops, was tested for its sensitivity to population density during nymph and adult stages. Nymphs reared to adulthood under increasing densities in laboratory conditions exhibited incremental delays in maturation, heightened mortality rates, and reductions in body mass and various size parameters. In contrast, gonadal activity in both males and females rose with initial density increases. Supplemental nutrients provided to the nymphs failed to offset the negative effects of high density, suggesting that contact frequency, rather than resource partitioning, may be the primary stress. Unlike nymphs, newly eclosed adults exposed to increasing population densities did not suffer negative physiological effects; body mass, mortality rates and patterns of ovipositional activity were unchanged. Collectively, these results indicate that population density can dramatically influence Lygus development, but the specific effects are stage-dependent
Dilaton EFT framework for lattice data
We develop an effective-field-theory (EFT) framework to analyze the spectra emerging from lattice simulations of a large class of confining gauge theories. Simulations of these theories, for which the light-fermion count is not far below the critical value for transition to infrared conformal behavior, have indicated the presence of a remarkably light singlet scalar particle. We incorporate this particle by including a scalar field in the EFT along with the Nambu-Goldstone bosons (NGB's), and discuss the application of this EFT to lattice data. We highlight the feature that data on the NGB's alone can tightly restrict the form of the scalar interactions. As an example, we apply the framework to lattice data for an SU(3) gauge theory with eight fermion flavors, concluding that the EFT can describe the data well
Seeking legitimacy through CSR: Institutional Pressures and Corporate Responses of Multinationals in Sri Lanka
Arguably, the corporate social responsibility (CSR) practices of multinational enterprises (MNEs) are influenced by a wide range of both internal and external factors. Perhaps most critical among the exogenous forces operating on MNEs are those exerted by state and other key institutional actors in host countries. Crucially, academic research conducted to date offers little data about how MNEs use their CSR activities to strategically manage their relationship with those actors in order to gain legitimisation advantages in host countries. This paper addresses that gap by exploring interactions between external institutional pressures and firm-level CSR activities, which take the form of community initiatives, to examine how MNEs develop their legitimacy-seeking policies and practices. In focusing on a developing country, Sri Lanka, this paper provides valuable insights into how MNEs instrumentally utilise community initiatives in a country where relationship-building with governmental and other powerful non-governmental actors can be vitally important for the long-term viability of the business. Drawing on neo-institutional theory and CSR literature, this paper examines and contributes to the embryonic but emerging debate about the instrumental and political implications of CSR. The evidence presented and discussed here reveals the extent to which, and the reasons why, MNEs engage in complex legitimacy-seeking relationships with Sri Lankan institutions
Ezrin interacts with the SARS coronavirus spike protein and restrains infection at the entry stage
© 2012 Millet et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Entry of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and its envelope fusion with host cell membrane are controlled by a series of complex molecular mechanisms, largely dependent on the viral envelope glycoprotein Spike (S). There are still many unknowns on the implication of cellular factors that regulate the entry process. Methodology/Principal Findings: We performed a yeast two-hybrid screen using as bait the carboxy-terminal endodomain of S, which faces the cytosol during and after opening of the fusion pore at early stages of the virus life cycle. Here we show that the ezrin membrane-actin linker interacts with S endodomain through the F1 lobe of its FERM domain and that both the eight carboxy-terminal amino-acids and a membrane-proximal cysteine cluster of S endodomain are important for this interaction in vitro. Interestingly, we found that ezrin is present at the site of entry of S-pseudotyped lentiviral particles in Vero E6 cells. Targeting ezrin function by small interfering RNA increased S-mediated entry of pseudotyped particles in epithelial cells. Furthermore, deletion of the eight carboxy-terminal amino acids of S enhanced S-pseudotyped particles infection. Expression of the ezrin dominant negative FERM domain enhanced cell susceptibility to infection by SARS-CoV and S pseudotyped particles and potentiated S-dependent membrane fusion. Conclusions/Significance: Ezrin interacts with SARS-CoV S endodomain and limits virus entry and fusion. Our data present a novel mechanism involving a cellular factor in the regulation of S-dependent early events of infection.This work was supported by the Research Grant Council of Hong Kong (RGC#760208)and the RESPARI project of the International Network of Pasteur Institutes
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The effects of ocular magnification on Spectralis spectral domain optical coherence tomography scan length
Purpose
The purpose of this study was to assess the effects of incorporating individual ocular biometry measures of corneal curvature, refractive error, and axial length on scan length obtained using Spectralis spectral domain optical coherence tomography (SD-OCT).
Methods
Two SD-OCT scans were acquired for 50 eyes of 50 healthy participants, first using the Spectralis default keratometry (K) setting followed by incorporating individual mean-K values. Resulting scan lengths were compared to predicted scan lengths produced by image simulation software, based on individual ocular biometry measures including axial length.
Results
Axial length varied from 21.41 to 29.04 mm. Spectralis SD-OCT scan lengths obtained with default-K ranged from 5.7 to 7.3 mm, and with mean-K from 5.6 to 7.6 mm. We report a stronger correlation of simulated scan lengths incorporating the subject’s mean-K value (ρ = 0.926, P < 0.0005) compared to Spectralis default settings (ρ = 0.663, P < 0.0005).
Conclusions
Ocular magnification appears to be better accounted for when individual mean-K values are incorporated into Spectralis SD-OCT scan acquisition versus using the device’s default-K setting. This must be considered when taking area measurements and lateral measurements parallel to the retinal surface
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