Inter-scan reproducibility of coronary calcium measurement using Multi Detector-Row Computed Tomography (MDCT)

Purpose: To assess inter-scan reproducibility of coronary calcium measurements obtained from Multi Detector-Row CT (MDCT) images and to evaluate whether this reproducibility is affected by different measurement protocols, slice thickness, cardiovascular risk factors and/or technical variables. Design: Cross-sectional study with repeated measurements. Materials and methods: The study population comprised 76 healthy women. Coronary calcium was assessed in these women twice in one session using 16-MDCT (Philips Mx 8000 IDT 16). Images were reconstructed with 1.5 mm slice thickness and 3.0 mm slice thickness. The 76 repeated scans were scored. The Agatston score, a volume measurement and a mass measurement were assessed. Reproducibility was determined by estimation of mean, absolute, relative difference, the weighted kappa value for agreement and the Intra-class correlation coefficient (ICCC). Results: Fifty-five participants (72.4%) had a coronary calcification of more than zero in Agatston (1.5 mm slice thickness). The reproducibility of coronary calcium measurements between scans in terms of ranking was excellent with Intra-class correlation coefficients of >0.98, and kappa values above 0.80. The absolute difference in calcium score between scans increased with increasing calcium levels, indicating that measurement error increases with increasing calcium levels. However, no relation was found between the mean difference in scores and calcium levels, indicating that the increase in measurement error is likely to result in random misclassification in calcium score. Reproducibility results were similar for 1.5 mm slices and for 3.0 mm slices, and equal for Agatston, volume and mass measurements. Conclusion: Inter-scan reproducibilility of measurement of coronary calcium using images from MDCT is excellent, irrespective of slice thickness and type of calcium parameter

Candidate gene association study in pediatric acute lymphoblastic leukemia evaluated by Bayesian network based Bayesian multilevel analysis of relevance

Background: We carried out a candidate gene association study in pediatric acute lymphoblastic leukemia (ALL) to identify possible genetic risk factors in a Hungarian population. Methods: The results were evaluated with traditional statistical methods and with our newly developed Bayesian network based Bayesian multilevel analysis of relevance (BN-BMLA) method. We collected genomic DNA and clinical data from 543 children, who underwent chemotherapy due to ALL, and 529 healthy controls. Altogether 66 single nucleotide polymorphisms (SNPs) in 19 candidate genes were genotyped. Results: With logistic regression, we identified 6 SNPs in the ARID5B and IKZF1 genes associated with increased risk to B-cell ALL, and two SNPs in the STAT3 gene, which decreased the risk to hyperdiploid ALL. Because the associated SNPs were in linkage in each gene, these associations corresponded to one signal per gene. The odds ratio (OR) associated with the tag SNPs were: OR = 1.69, P = 2.22x10-7 for rs4132601 (IKZF1), OR = 1.53, P = 1.95x10-5 for rs10821936 (ARID5B) and OR = 0.64, P = 2.32x10-4 for rs12949918 (STAT3). With the BN-BMLA we confirmed the findings of the frequentist-based method and received additional information about the nature of the relations between the SNPs and the disease. E.g. the rs10821936 in ARID5B and rs17405722 in STAT3 showed a weak interaction, and in case of T-cell lineage sample group, the gender showed a weak interaction with three SNPs in three genes. In the hyperdiploid patient group the BN-BMLA detected a strong interaction among SNPs in the NOTCH1, STAT1, STAT3 and BCL2 genes. Evaluating the survival rate of the patients with ALL, the BN-BMLA showed that besides risk groups and subtypes, genetic variations in the BAX and CEBPA genes might also influence the probability of survival of the patients. Conclusions: In the present study we confirmed the roles of genetic variations in ARID5B and IKZF1 in the susceptibility to B-cell ALL. With the newly developed BN-BMLA method several gene-gene, gene-phenotype and phenotype-phenotype connections were revealed. We showed several advantageous features of the new method, and suggested that in gene association studies the BN-BMLA might be a useful supplementary to the traditional frequentist-based statistical method

Uncovering Dangerous Cheats: How Do Avian Hosts Recognize Adult Brood Parasites?

BACKGROUND: Co-evolutionary struggles between dangerous enemies (e.g., brood parasites) and their victims (hosts) lead to the emergence of sophisticated adaptations and counter-adaptations. Salient host tricks to reduce parasitism costs include, as front line defence, adult enemy discrimination. In contrast to the well studied egg stage, investigations addressing the specific cues for adult enemy recognition are rare. Previous studies have suggested barred underparts and yellow eyes may provide cues for the recognition of cuckoos Cuculus canorus by their hosts; however, no study to date has examined the role of the two cues simultaneously under a consistent experimental paradigm. METHODOLOGY/PRINCIPAL FINDINGS: We modify and extend previous work using a novel experimental approach--custom-made dummies with various combinations of hypothesized recognition cues. The salient recognition cue turned out to be the yellow eye. Barred underparts, the only trait examined previously, had a statistically significant but small effect on host aggression highlighting the importance of effect size vs. statistical significance. CONCLUSION: Relative importance of eye vs. underpart phenotypes may reflect ecological context of host-parasite interaction: yellow eyes are conspicuous from the typical direction of host arrival (from above), whereas barred underparts are poorly visible (being visually blocked by the upper part of the cuckoo's body). This visual constraint may reduce usefulness of barred underparts as a reliable recognition cue under a typical situation near host nests. We propose a novel hypothesis that recognition cues for enemy detection can vary in a context-dependent manner (e.g., depending on whether the enemy is approached from below or from above). Further we suggest a particular cue can trigger fear reactions (escape) in some hosts/populations whereas the same cue can trigger aggression (attack) in other hosts/populations depending on presence/absence of dangerous enemies that are phenotypically similar to brood parasites and costs and benefits associated with particular host responses

Effect of partners’ disgust responses on psychological wellbeing in cancer patients

The aim of this study was to explore quantitatively the relationship between disgust responses in cancer patients and their partners, and in turn their relationship to patients’ psychological well-being. We recruited 50 participants with heterogeneous cancer diagnoses and their partners from cancer-related groups (e.g., charities). Patients completed questionnaires to determine levels of disgust propensity, disgust sensitivity, self-disgust, and symptoms of anxiety and depression. Disgust propensity and sensitivity were also assessed in their partners. Partners’ disgust sensitivity was significantly positively correlated with cancer patients’ self-disgust, disgust propensity, and depression. Path analyses suggested that patients’ self-disgust plays a role in mediating the effect of partners’ disgust sensitivity on patients’ psychological well-being. This study provides the first quantitative evidence that psychological well-being in cancer patients is contingent on their partners’ sensitivity to disgust, and that patients’ self-disgust plays a mediating role. Focusing therapeutically on disgust responses could well be beneficial to people with cancer

1D-3 mechanisms responsible for ultrasound-accelerated fibrinolysis in the presence and absence of Optison™

Ultrasound at frequencies greater than 1 MHz is known to accelerate clot dissolution by fibrinolytic agents. It is speculated that ultrasound accelerates enzymatic fibrinolysis primarily through non-thermal mechanisms by increasing transport of drug molecules into the clot. To elucidate the mechanisms of ultrasound-accelerated enzymatic fibrinolysis, the role of both stable and inertial cavitation were investigated during in vitro fibrinolysis by ultrasound in combination with recombinant tissue plasminogen activator (rt-PA) in the presence and absence of Optison™. A unique treatment configuration was used in which ultrasound, rt-PA, and contrast agent were all applied to the interior of a plasma clot. rt-PA was injected directly into the clot at a concentration of 5,000 IU/mL. Optison™ was dispersed throughout the clot at a concentration of 2.6times106 bubbles/mL. The ultrasound exposure consisted of 1.7 MHz pulsed ultrasound with 1.5 MPa spatial-peak peak-negative pressure applied for 30 minutes by a transducer-tipped catheter. Lysis efficacy was measured as clot weight reduction. Cavitational mechanisms were investigated by passively monitoring acoustic emissions from the clot using a focused broadband hydrophone, and quantifying levels of subharmonic emission and broadband noise, indicators for stable and inertial cavitation, respectively. In the absence of Optison™, ultrasound plus rt-PA resulted in 45 plusmn 19% lysis enhancement relative to lysis from rt-PA alone. Cavitation signals were not detected in the corresponding radiated acoustic signal, indicating a role for non-cavitational mechanical effects of ultrasound. The addition of Optison™ significantly increased lysis enhancement to 88 plusmn 25%. Broadband noise elevation was present only at the start of the exposure, while low-level subharmonic emissions persisted throughout. Additional experiments suggested that the lysis enhancement in the presence of Optison™ was correlated to the subharmonic emission rather than the broadband noise, indicating a role for stable cavitation. Mechanisms related to stable cavitation, such as microstreaming near oscillating bubbles, may enhance fibrinolysis by promoting local mass transfer and thus increasing the rate of penetration of rt-PA throughout the clot matri

Cavitational mechanisms in ultrasound-accelerated fibrinolysis

The role of both inertial and stable cavitation was investigated during in vitro ultrasound-accelerated fibrinolysis by recombinant tissue plasminogen activator (rt-PA) in the presence and absence of Optison™. A unique treatment configuration applied ultrasound, rt-PA and Optison™ to the interior of a plasma clot. Lysis efficacy was measured as clot weight reduction. Cavitational mechanisms were investigated by monitoring subharmonic and broadband noise. In the absence of Optison™, 1.7 MHz pulsed ultrasound with 1.5 MPa peak-negative pressure applied for 30 min resulted in 45 ± 19% lysis enhancement relative to rt-PA alone. Cavitation was not detected, indicating a role of noncavitational effects of ultrasound. The addition of Optison™ increased lysis enhancement to 88 ± 25%. Inertial cavitation was present only at the start of the exposure, while low-amplitude subharmonic emissions persisted throughout. Additional protocols suggested a possible correlation between the increased lysis in the presence of Optison™ and the subharmonic emission, indicating a potentially important role of stable rather than inertial cavitation in microbubble-enhanced ultrasound-accelerated rt-PA-mediated thrombolysis

Cavitational mechanisms in ultrasound-accelerated fibrinolysis

The role of both inertial and stable cavitation was investigated during in vitro ultrasound-accelerated fibrinolysis by recombinant tissue plasminogen activator (rt-PA) in the presence and absence of Optison™. A unique treatment configuration applied ultrasound, rt-PA and Optison™ to the interior of a plasma clot. Lysis efficacy was measured as clot weight reduction. Cavitational mechanisms were investigated by monitoring subharmonic and broadband noise. In the absence of Optison™, 1.7 MHz pulsed ultrasound with 1.5 MPa peak-negative pressure applied for 30 min resulted in 45 ± 19% lysis enhancement relative to rt-PA alone. Cavitation was not detected, indicating a role of noncavitational effects of ultrasound. The addition of Optison™ increased lysis enhancement to 88 ± 25%. Inertial cavitation was present only at the start of the exposure, while low-amplitude subharmonic emissions persisted throughout. Additional protocols suggested a possible correlation between the increased lysis in the presence of Optison™ and the subharmonic emission, indicating a potentially important role of stable rather than inertial cavitation in microbubble-enhanced ultrasound-accelerated rt-PA-mediated thrombolysis