Quality-of-life indicators at different scales: Theoretical background

The article is presenting the general analysis of the systems approach and model approaches for the development of QoL indicators and indices. In our study we propose the method of response function as a method of the construction of purposeful, credible integrated models from data and prior knowledge or information. The method of response function implies credible models in the sense that they are identifiable, and, hopefully, explains system output behaviour satisfactorily.Using response function method for the development of QoL models, we are able to obtain QoL indices as the direct output of the models.     

Automatic exposure control at single- and dual-heartbeat CTCA on a 320-MDCT volume scanner: Effect of heart rate,exposure phase window setting,and reconstruction algorithm

PurposeTo investigate whether electrocardiogram (ECG)-gated single- and dual-heartbeat computed tomography coronary angiography (CTCA) with automatic exposure control (AEC) yields images with uniform image noise at reduced radiation doses.Materials and methodsUsing an anthropomorphic chest CT phantom we performed prospectively ECG-gated single- and dual-heartbeat CTCA on a second-generation 320-multidetector CT volume scanner. The exposure phase window was set at 75%, 70–80%, 40–80%, and 0–100% and the heart rate at 60 or 80 or corr80 bpm; images were reconstructed with filtered back projection (FBP) or iterative reconstruction (IR, adaptive iterative dose reduction 3D). We applied AEC and set the image noise level to 20 or 25 HU. For each technique we determined the image noise and the radiation dose to the phantom center.ResultsWith half-scan reconstruction at 60 bpm, a 70–80% phase window- and a 20-HU standard deviation (SD) setting, the imagenoise level and -variation along the z axis manifested similar curves with FBP and IR. With half-scan reconstruction, the radiation dose to the phantom center with 70–80% phase window was 18.89 and 12.34 mGy for FBP and 4.61 and 3.10 mGy for IR at an SD setting SD of 20 and 25 HU, respectively. At 80 bpm with two-segment reconstruction the dose was approximately twice that of 60 bpm at both SD settings. However, increasing radiation dose at corr80 bpm was suppressed to 1.39 times compared to 60 bpm.ConclusionAEC at ECG-gated single- and dual-heartbeat CTCA controls the image noise at different radiation dose.     

Spectral optimization of iodine-enhanced CT: Quantifying the effect of tube voltage on image quality and radiation exposure determined at an anthropomorphic phantom

PurposeTo provide an experimental basis for spectral optimization of iodine-enhanced CT by a quantitative analysis of image quality and radiation dose characteristics consistently measured for a large variety of scan settings at an anthropomorphic phantom.MethodsCT imaging and thermoluminescent dosimetry were performed at an anthropomorphic whole-body phantom with iodine inserts for different tube voltages (U, 70–140 kV) and current-time products (Q, 60–300 mAs). For all U-Q combinations, the iodine contrast (C), the noise level (N) and, from these, the contrast-to-noise ratio (CNR) of reconstructed CT images were determined and parameterized as a function of U, Q or the measured absorbed dose (D). Finally, two characteristic curves were derived that give the relative increase of CNR at constant D and the relative decrease of D at constant CNR when lowering U.ResultsLowering U affects the measured CNR only slightly but markedly reduces D. For example, reducing U from 120 kV to 70 kV increases the CNR at constant D by a factor of nearly 1.8 or, alternatively, reduces D at constant CNR by a factor of nearly 5.ConclusionSpectral optimization by lowering U is an effective approach to attain the necessary CNR for a specific diagnostic task at hand while at the same time reducing radiation exposure as far as practically achievable. The characteristic curves derived in this study from extensive measurements at a reference ‘person’ can support CT users in an easy-to-use manner to select an appropriate voltage for various clinical scenarios.     

Quality control and statistical modeling for environmental epigenetics: A study on in utero lead exposure and DNA methylation at birth

DNA methylation data assayed using pyrosequencing techniques are increasingly being used in human cohort studies to investigate associations between epigenetic modifications at candidate genes and exposures to environmental toxicants and to examine environmentally-induced epigenetic alterations as a mechanism underlying observed toxicant-health outcome associations. For instance, in utero lead (Pb) exposure is a neurodevelopmental toxicant of global concern that has also been linked to altered growth in human epidemiological cohorts; a potential mechanism of this association is through alteration of DNA methylation (e.g., at growth-related genes). However, because the associations between toxicants and DNA methylation might be weak, using appropriate quality control and statistical methods is important to increase reliability and power of such studies. Using a simulation study, we compared potential approaches to estimate toxicant-DNA methylation associations that varied by how methylation data were analyzed (repeated measures vs. averaging all CpG sites) and by method to adjust for batch effects (batch controls vs. random effects). We demonstrate that correcting for batch effects using plate controls yields unbiased associations, and that explicitly modeling the CpG site-specific variances and correlations among CpG sites increases statistical power. Using the recommended approaches, we examined the association between DNA methylation (in LINE-1 and growth related genes IGF2, H19 and HSD11B2) and 3 biomarkers of Pb exposure (Pb concentrations in umbilical cord blood, maternal tibia, and maternal patella), among mother-infant pairs of the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) cohort (n = 247). Those with 10 μg/g higher patella Pb had, on average, 0.61% higher IGF2 methylation (P = 0.05). Sex-specific trends between Pb and DNA methylation (P < 0.1) were observed among girls including a 0.23% increase in HSD11B2 methylation with 10 μg/g higher patella Pb.     

Quality control and statistical modeling for environmental epigenetics: A study on in utero lead exposure and DNA methylation at birth

DNA methylation data assayed using pyrosequencing techniques are increasingly being used in human cohort studies to investigate associations between epigenetic modifications at candidate genes and exposures to environmental toxicants and to examine environmentally-induced epigenetic alterations as a mechanism underlying observed toxicant-health outcome associations. For instance, in utero lead (Pb) exposure is a neurodevelopmental toxicant of global concern that has also been linked to altered growth in human epidemiological cohorts; a potential mechanism of this association is through alteration of DNA methylation (e.g., at growth-related genes). However, because the associations between toxicants and DNA methylation might be weak, using appropriate quality control and statistical methods is important to increase reliability and power of such studies. Using a simulation study, we compared potential approaches to estimate toxicant-DNA methylation associations that varied by how methylation data were analyzed (repeated measures vs. averaging all CpG sites) and by method to adjust for batch effects (batch controls vs. random effects). We demonstrate that correcting for batch effects using plate controls yields unbiased associations, and that explicitly modeling the CpG site-specific variances and correlations among CpG sites increases statistical power. Using the recommended approaches, we examined the association between DNA methylation (in LINE-1 and growth related genes IGF2, H19 and HSD11B2) and 3 biomarkers of Pb exposure (Pb concentrations in umbilical cord blood, maternal tibia, and maternal patella), among mother-infant pairs of the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) cohort (n = 247). Those with 10 μg/g higher patella Pb had, on average, 0.61% higher IGF2 methylation (P = 0.05). Sex-specific trends between Pb and DNA methylation (P < 0.1) were observed among girls including a 0.23% increase in HSD11B2 methylation with 10 μg/g higher patella Pb.     

Eagerness for Physical Activity Scale: Theoretical background and validation

The Eagerness for Physical Activity Scale (EPAS) validated in this study is based on the belief that eagerness for physical activity should be seen as a major outcome of interventions and physical activity contexts. The aim of the study was to introduce the concept of eagerness into physical activity research, to validate EPAS, and to explore its relationship with maximal oxygen uptake (VO_2max) and motivation. A multi-study validation approach was used. Convergent and discriminant validity was supported and the scale displayed high internal consistency across all studies. When controlling for self-determined motivation, eagerness for physical activity related positively to VO_2max, thus supporting incremental validity above and beyond intrinsic motivation, identified regulation, extrinsic regulation, and a-motivation. Based on our results we recommend not only the application of EPAS in the assessment of how intervention programs and regular types of activity contexts affect people of all ages, but also the introduction of the concept of eagerness into physical activity and health research and policy in general.     

Marine protected areas: Theoretical background for design and operation

This review paper deals with the problem of the design and operation of marine reserves in the context of modern views on the hierarchical organization of marine ecosystems. The state of the art in the theoretical aspect of the establishment and development of marine protected areas (MPAs) is discussed. Despite the increasing number of publications on MPAs, which are mainly focused on social and economic issues, studies devoted to the ecological bases for the establishment and operation of marine reserves are still scarce. However, the low efficiency of the existing MPAs and their systems may be a result of the lack of an ecological background in MPA designs. Recent threats to the diversity of marine organisms are analyzed, and changes in the relative significance of anthropogenic factors affecting the marine biological diversity are assessed. The hierarchical nature of and the existence of characteristic spatial scales in the marine ecosystems are critical issues that must be taken into account together with scale-oriented analysis of the anthropogenic threats. On the basis of the scale-oriented concept of the marine ecosystems, new theoretical approaches to the design and operation of MPAs are formulated. In particular, theoretical bases for the estimation of the minimal size of marine reserves and a hierarchical approach to the design of MPA systems are proposed. Formal schemes of classification of sea bottom communities (The Marine Habitat Classification for Britain and Ireland and EUNIS) are discussed.     

A novel design of ultrafast micro-CT system based on carbon nanotube: A feasibility study in phantom

Artifacts induced by respiratory motion during routine diagnosis severely degrades the image quality. The increase of scanning speed plays an important role to avoid motion artifacts. Limited to the mechanical structure of conventional CT, the increase of gantry rotational speed is unsustainable and a more feasible way is to increase the number of X-ray sources and detectors like the dual-source CT. This paper focuses on high-speed scanning CT and proposes a novel ultrafast micro-CT (UMCT) system based on carbon nanotube (CNT). At each exposure position, all of the X-ray sources are fast activated by turns and the flat-panel detectors collect the corresponding projection data. Then, the gantry will be contrarotated 40° to prepare for the next exposure until the rotation covers full 360°. Because each exposure is very fast, the organ motions of in vivo human body can be greatly reduced. This paper introduces the UMCT system design, image reconstruction algorithm and experimental results. Simulation experiment was also carried out on UMCT system. The result validated the feasibility of the UMCT system.     

Theoretical study on isomerization and peptide bond cleavage at aspartic residue

Isomerization and peptide bond cleavage at aspartic residue (Asp) in peptide models have been reported. In this study, the mechanisms and energies concerning the isomerization and peptide bond cleavage at Asp residue were investigated by the density functional theory (DFT) at B3LYP/6-311++G(d,p). The integral equation formalism-polarizable continuum model (IEF-PCM) was utilized to calculate solvation effect by single-point calculation of the gas-phase B3LYP/6-311++G(d,p)-optimized structure. Mechanisms and energies of the dehydration in isomerization reaction of Asp residue were comparatively analyzed with the deamidation reaction of Asn residue. The results show that the succinimide intermediate was formed preferentially through the step-wise reaction via the tetrahedral intermediate. The cleavage at C-terminus is more preferential than those at N-terminus. In comparison to isomerization, peptide bond cleavage is ～20 kcal mol^?1 and lower in activation barrier than the isomerization. So, in this case, the isomerization of Asp is inhibited by the peptide bond cleavage.     

Sex ratio at birth, polygyny, and fertility: a cross-national study

The sex ratio at birth may reflect frequency of intercourse that affects the timing of conception. If so, cross-national variation in polygyny and fertility might account for country differences in secondary sex ratios. Consistent with the timing of intercourse hypothesis, the birth sex ratios of 148 countries declined with total fertility rates and polygyny intensity, and increased with contraception use in correlational analysis. Regression analysis confirmed that polygyny was a negative predictor of the sex ratio (and contraception was a positive predictor), with level of economic development and mother's age controlled, but the effects disappeared with total fertility added to the equation. The sex ratio evidently declines with increases in fertility because more children are born at a later birth order when frequency of intercourse is lower.     

Theoretical study on the body form and swimming pattern of Anomalocaris based on hydrodynamic simulation

Anomalocarid arthropod is the largest known predatory animal of middle Cambrian. Studies on Anomalocaris have been piled up in the past two decades since the first reasonable reconstruction had achieved in 1980s. Recent finding of legs beneath lobes on Parapeytoia Yunnanensis shows arthropod affinities, however, many researchers believe that it must be a powerful swimmer by the use of developed lobes. In this work, we investigate swimming behaviour of Anomalocaris in water by performing hydrodynamical calculation. As a result of simulation using moving particle method possible swimming motion of Anomalocaris is obtained. In the computer we can change the morphology from known bauplan of Anomalocaris found as fossil record. It makes us possible to discuss on the variants of Anomalocaris at the intermediate state of evolution process. Such new methodology using computer reveals how and from where Anomalocaris evolved.     

H-Y antigen in the study of sex determination and control of sex ratio

It has been proposed, on the basis of widespread phylogenetic conservation, that H-Y antigen is the inducer of primary sex, causing the undifferentiated XY gonad to become a testis in male heterogametic species such as the human and bovine. That proposition has withstood extensive testing in vivo and in vitro. Freemartin gonads are H-Y⁺, for example, and masculinization of the freemartin gonad has been attributed to soluble H-Y, borne and transmitted in the serum of the bull twin, and bound in ovarian receptors of the female. We have applied monoclonal H-Y antibodies to the identification of gender in embryos of the bovine. Our preliminary results imply presence of H-Y in bovine embryos of the morula and blastocyst stages recovered at about 6–12 days of gestation. Assignment of H-Y phenotype -- positive in males and negative in females -- allows selective implantation of male and female during embryo transfer. Thus in an early study, we correctly identified gender in 6 of 7 calves born healthy at term, after transfer of 8 blastocysts.     

Theoretical note: the C/T ratio in artificial neural networks

This paper describes computer simulations of the effect of the C/T ratio on acquisition rate in artificial neural networks. The networks consisted of neural processing elements that functioned according to a neurocomputational model whose learning rule is consistent with information on dopaminergic mechanisms of reinforcement. In Simulation 1, three comparisons were made: constant C and variable T, variable C and constant T, and a constant C/T with variable C and T. In the last two comparisons, C was manipulated by changing the probability of reinforcement within the intertrial interval (ITI), in the absence of the conditioned stimulus (CS). Acquisition rate tended to increase with C/T, and the invariant ratio had no effect. In Simulation 2, C was manipulated by changing the ITI, with continuous reinforcement in the presence of the CS and no reinforcements in its absence. Results were comparable to those obtained in Simulation 1. Simulation 3 further explored the effect of the invariant ratio, but with larger absolute values of C and T, which slowed acquisition significantly. The results parallel some experimental findings and theoretical implications of the Gibbon-Balsam model, showing that they can emerge from the moment-to-moment dynamics of a neural-network model. In contrast to that model, however, Simulation 3 suggests that the effect of invariant C/T ratios may be bounded.     

Accuracy of 2-hydroxyglutarate quantification by short-echo proton-MRS at 3 T: A phantom study

PurposeWe set out to investigate the potential confounding effect of variable concentration of N-acetyl-l-aspartate (NAA) and Glutamate (Glu) on measurement of the brain oncometabolite 2-hydroxyglutarate (2HG) using a standard MRS protocol. This issue may arise due to spectral overlap at clinical magnetic field strengths and thus complicate the usage of 2HG as a putative biomarker of gliomas bearing mutations of the isocitrate dehydrogenase (IDH) 1 and 2 genes.MethodsSpectra from 25 phantoms (50 mL falcon test tubes) containing a range of known concentrations of 2HG, NAA and Glu were acquired using a clinical 3 T scanner with a quadrature head coil, single-voxel point-resolved spectroscopy sequence with TE = 30 ms. Metabolite concentrations were estimated by linear combination analysis and a simulated basis set.ResultsNAA and Glu concentrations can have a significant confounding effect on 2HG measurements, whereby the negative changes in concentration of these metabolites typically observed in (peri)lesional areas can lead to under-estimation of 2HG concentration with respect to spectra acquired in presence of physiological levels of NAA and Glu.ConclusionThe confounding effect of NAA and Glu concentration changes needs to be considered: in patients, it may mask the presence of 2HG at low concentrations, however it is not expected to lead to false positives. 2HG data acquired using standard short echo-time MRS protocols should be considered with caution.     

Metabolic control analysis of the penicillin biosynthetic pathway: the influence of the lld-ACV:bisACV ratio on the flux control

An extended kinetic model for the first two steps of the penicillin biosynthetic pathway in Penicillium chrysogenum is set up. It includes the formation and reduction of the dimer bis--(l--aminoadipyl)-l-cysteinyl-d-valine (bisACV) from the first pathway intermediate lld-ACV and their parallel inhibition of the enzyme ACV synthetase (ACVS). The kinetic model is based on Michaelis-Menten type kinetics, with non-competitive inhibition of the ACVS by both lld-ACV and bisACV, and competitive inhibition of the isopenicillin N synthetase (IPNS) by glutathione. The inhibition constant of lld-ACV, K_ACV is determined to be 0.54 mm. With the kinetic model metabolic control analysis is performed to identify the distribution of rate-control in the pathway at all ratios of lld-ACV:bisACV. It is concluded that the flux control totally resides at the IPNS. This is a result of the regulation of the ACVS by both the lld-ACV and bisACV demanding a higher flux through the IPNS enzyme to alleviate their inhibition. The measurement of an intracellular ratio of lld-ACV:bisACV to be in the range of 1–2 moles per moles emphasises the importance of a fast conversion of lld-ACV to IPN, and accumulation of lld-ACV above the K_m-value of the IPNS should therefore be avoided.     

An immunological and morphological study of focal staphylococcal infection against a background of long-term exposure to the herbicide linuron

Small doses of long-term injection of herbicide linuron causes the appearance of secondary immunodeficiency. It is manifested in histological and ultrastructural determination of thymus, severe suppression of immunological indices. Epithelial nurse-cells damage takes place in thymus, the contacts between epithelial cells are destroyed, the reforming of microvessels (their endothelium) occurs which causes the deterioration of vessels penetration and the growth of connective tissue. Against this background a more rapid development of experimental staphylococcus abscesses is observed in animals, the reparation phase being absent.     

Dosimetric impact of hysteresis on lung cancer tomotherapy: A moving phantom study

PurposeTo investigate the dosimetric impact of hysteresis on lung cancer tomotherapy.MethodsMeasurements were acquired using MapCheck with an XY4D motion simulation table. Six hysteresis states (0, π/32, π/16, π/8, 3π/16, and π/4) were considered with sinusoidal motions in the superior–inferior and left–right orientations. The measured data were analyzed both globally (from all detectors) and structure-by-structure in the measurement plane. The dose difference (DD) analysis method with local normalization in the absolute dose mode with a DD threshold of 6 cGy was adopted to analyze each hysteresis vs. static state (H(1)S) and nonzero vs. zero hysteresis (H(1)0). The threshold was 10% for all analyses. Wilcoxon signed rank tests with significance level p = 0.05 were used for statistical analysis.ResultsThe DD analysis of each H(1)S mostly indicated that the passing rate differed between structures but was similar between hysteresis states. The DD analysis of H(1)0 showed that the passing rate decreased with increasing hysteresis. The differences between larger hysteresis (≥3π/16) and other states were significant for comparisons between global, left lung, chest wall, and target. Both analyses showed that the DD distribution changed with hysteresis.ConclusionsHysteresis difference causes the DD distribution to change. Structural difference had more impact than hysteresis state difference on hysteresis motion vs. static comparisons. Remarkable effects on nonzero vs. zero hysteresis comparisons were only seen for structures closely related to the target at large hysteresis. Small organs at risk that are close to the target need to be considered further.     

Personal exposure to mobile phone frequencies and well-being in adults: a cross-sectional study based on dosimetry

The use of mobile phone telecommunication has increased in recent years. In parallel, there is growing concern about possible adverse health effects of cellular phone networks. We used personal dosimetry to investigate the association between exposure to mobile phone frequencies and well-being in adults. A random population-based sample of 329 adults living in four different Bavarian towns was assembled for the study. Using a dosimeter (ESM-140 Maschek Electronics), we obtained an exposure profile over 24 h for three mobile phone frequency ranges (measurement interval 1 s, limit of determination 0.05 V/m). Exposure levels over waking hours were totalled and expressed as mean percentage of the International Commission on Non-Ionizing Radiation Protection (ICNIRP) reference level. Each participant reported acute symptoms in a day-long diary. Data on five groups of chronic symptoms and potential confounders were assessed during an interview. The overall exposure to high-frequency electromagnetic fields was markedly below the ICNIRP reference level. We did not find any statistically significant association between the exposure and chronic symptoms or between the exposure and acute symptoms. Larger studies using mobile phone dosimetry are warranted to confirm these findings.