A novel method for comparing radiation dose and image quality, between and within different X-ray units in a series of hospitals

Objectives: To develop a novel method for comparing radiation dose and image quality (IQ) to evaluate adult chest X-ray (CXR) imaging among several hospitals. Methods: CDRAD 2.0 phantom was used to acquire images in eight hospitals (17 digital X-ray units) using local adult CXR protocols. IQ was represented by image quality figure inverse (IQFinv), measured using CDRAD analyser software. Signal to noise ratio (SNR), contrast to noise ratio (CNR) and conspicuity index (CI) were calculated as additional measures of IQ. Incident air kerma (IAK) was calculated using a solid-state dosimeter for each acquisition. Figure of merit (FOM) was calculated to provide a single estimation of IQ and radiation dose. Results: IQ, radiation dose and FOM varied considerably between hospitals and X-ray units. For IQFinv, the mean (range) between and within the hospitals were 1.42 (0.83-2.18) and 1.87 (1.52-2.18), respectively. For IAK, the mean (range) between and within the hospitals were 93.56 (17.26 to 239.15) µGy and 180.85 (122.58-239.15) µGy, respectively. For FOM, the mean (range) between and within hospitals were 0.05 (0.01 to 0.14) and 0.03 (0.02-0.05), respectively. Conclusions: The suggested method for comparing IQ and dose using FOM concept along with the new proposed FOM, is a valid, reliable and effective approach for monitoring and comparing IQ and dose between and within hospitals. It is also can be beneficial for the optimisation of X-ray units in clinical practice. Further optimisation for the hospitals /X-ray units with low FOM are required to minimise radiation dose without degrading IQ

Keep an eye on your hands: on the role of visual mechanisms in processing of haptic space

The present paper reviews research on a haptic orientation processing. Central is a task in which a test bar has to be set parallel to a reference bar at another location. Introducing a delay between inspecting the reference bar and setting the test bar leads to a surprising improvement. Moreover, offering visual background information also elevates performance. Interestingly, (congenitally) blind individuals do not or to a weaker extent show the improvement with time, while in parallel to this, they appear to benefit less from spatial imagery processing. Together this strongly points to an important role for visual processing mechanisms in the perception of haptic inputs

Thermal- and Oxidative Stress Causes Enhanced Release of NKG2D Ligand-Bearing Immunosuppressive Exosomes in Leukemia/Lymphoma T and B Cells

Immune evasion from NK surveillance related to inadequate NK-cell function has been suggested as an explanation of the high incidence of relapse and fatal outcome of many blood malignancies. In this report we have used Jurkat and Raji cell lines as a model for studies of the NKG2D receptor-ligand system in T-and B cell leukemia/lymphoma. Using real-time quantitative RT-PCR and immunoflow cytometry we show that Jurkat and Raji cells constitutively express mRNA and protein for the stress-inducible NKG2D ligands MICA/B and ULBP1 and 2, and up-regulate the expression in a cell-line specific and stress-specific manner. Furthermore, we revealed by electron microscopy, immunoflow cytometry and western blot that these ligands were expressed and secreted on exosomes, nanometer-sized microvesicles of endosomal origin. Acting as a decoy, the NKG2D ligand-bearing exosomes downregulate the in vitro NKG2D receptor-mediated cytotoxicity and thus impair NK-cell function. Interestingly, thermal and oxidative stress enhanced the exosome secretion generating more soluble NKG2D ligands that aggravated the impairment of the cytotoxic response. Taken together, our results might partly explain the clinically observed NK-cell dysfunction in patients suffering from leukemia/lymphoma. The adverse effect of thermal and oxidative stress, enhancing the release of immunosuppressive exosomes, should be considered when cytostatic and hyperthermal anti-cancer therapies are designed

Analytical techniques for multiplex analysis of protein biomarkers

Introduction: The importance of biomarkers for pharmaceutical drug development and clinical diagnostics is more significant than ever in the current shift toward personalized medicine. Biomarkers have taken a central position either as companion markers to support drug development and patient selection, or as indicators aiming to detect the earliest perturbations indicative of disease, minimizing therapeutic intervention or even enabling disease reversal. Protein biomarkers are of particular interest given their central role in biochemical pathways. Hence, capabilities to analyze multiple protein biomarkers in one assay are highly interesting for biomedical research. Areas covered: We here review multiple methods that are suitable for robust, high throughput, standardized, and affordable analysis of protein biomarkers in a multiplex format. We describe innovative developments in immunoassays, the vanguard of methods in clinical laboratories, and mass spectrometry, increasingly implemented for protein biomarker analysis. Moreover, emerging techniques are discussed with potentially improved protein capture, separation, and detection that will further boost multiplex analyses. Expert commentary: The development of clinically applied multiplex protein biomarker assays is essential as multi-protein signatures provide more comprehensive information about biological systems than single biomarkers, leading to improved insights in mechanisms of disease, diagnostics, and the effect of personalized medicine

Molecular Mechanisms Associated with Nicotine Pharmacology and Dependence.

Tobacco dependence is a leading cause of preventable disease and death worldwide. Nicotine, the main psychoactive component in tobacco cigarettes, has also been garnering increased popularity in its vaporized form, as derived from e-cigarette devices. Thus, an understanding of the molecular mechanisms underlying nicotine pharmacology and dependence is required to ascertain novel approaches to treat drug dependence. In this chapter, we review the field's current understanding of nicotine's actions in the brain, the neurocircuitry underlying drug dependence, factors that modulate the function of nicotinic acetylcholine receptors, and the role of specific genes in mitigating the vulnerability to develop nicotine dependence. In addition to nicotine's direct actions in the brain, other constituents in nicotine and tobacco products have also been found to alter drug use, and thus, evidence is provided to highlight this issue. Finally, currently available pharmacotherapeutic strategies are discussed, along with an outlook for future therapeutic directions to achieve to the goal of long-term nicotine cessation

Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes.

BACKGROUND: Pubertal growth patterns correlate with future health outcomes. However, the genetic mechanisms mediating growth trajectories remain largely unknown. Here, we modeled longitudinal height growth with Super-Imposition by Translation And Rotation (SITAR) growth curve analysis on ~ 56,000 trans-ancestry samples with repeated height measurements from age 5 years to adulthood. We performed genetic analysis on six phenotypes representing the magnitude, timing, and intensity of the pubertal growth spurt. To investigate the lifelong impact of genetic variants associated with pubertal growth trajectories, we performed genetic correlation analyses and phenome-wide association studies in the Penn Medicine BioBank and the UK Biobank. RESULTS: Large-scale growth modeling enables an unprecedented view of adolescent growth across contemporary and 20th-century pediatric cohorts. We identify 26 genome-wide significant loci and leverage trans-ancestry data to perform fine-mapping. Our data reveals genetic relationships between pediatric height growth and health across the life course, with different growth trajectories correlated with different outcomes. For instance, a faster tempo of pubertal growth correlates with higher bone mineral density, HOMA-IR, fasting insulin, type 2 diabetes, and lung cancer, whereas being taller at early puberty, taller across puberty, and having quicker pubertal growth were associated with higher risk for atrial fibrillation. CONCLUSION: We report novel genetic associations with the tempo of pubertal growth and find that genetic determinants of growth are correlated with reproductive, glycemic, respiratory, and cardiac traits in adulthood. These results aid in identifying specific growth trajectories impacting lifelong health and show that there may not be a single "optimal" pubertal growth pattern