Risk Assessment for Flight in Uncontrolled Airspace Under Visual Flight Rules

The paper attempts to assess the risk in the area of analysis which is the flight of general aviation (GA) aircraft carried out under Visual Flights Rules in the uncontrolled airspace. The flight, selected for further analysis, is a typical air operation performed in GA. The risk assessment was carried out in accordance with the risk management algorithm. The identification of hazard sources was made using a checklist of 123 questions about their occurrence. On this base a list of 37 threats identified in the presented area of analysis was obtained. The risk assessment was carried out by the MICE-RISK method. Among the defined threats, 16 threats fall into the accepted category, 15 threats are characterized by the tolerated category, and for 6 threats the category is defined as unaccepted. A dealing with risk methods were proposed. The re-evaluation indicated that the number of threats in particular categories are: 27, 6 and 6

Variant Allele Frequency Analysis of Circulating Tumor DNA as a Promising Tool in Assessing the Effectiveness of Treatment in Non-Small Cell Lung Carcinoma Patients

Despite the different possible paths of treatment, lung cancer remains one of the leading causes of death in oncological patients. New tools guiding the therapeutic process are under scientific investigation, and one of the promising indicators of the effectiveness of therapy in patients with NSCLC is variant allele frequency (VAF) analysis. VAF is a metric characterized as the measurement of the specific variant allele proportion within a genomic locus, and it can be determined using methods based on NGS or PCR. It can be assessed using not only tissue samples but also ctDNA (circulating tumor DNA) isolated from liquid biopsy. The non-invasive characteristic of liquid biopsy enables a more frequent collection of material and increases the potential of VAF analysis in monitoring therapy. Several studies have been performed on patients with NSCLC to evaluate the possibility of VAF usage. The research carried out so far demonstrates that the evaluation of VAF dynamics may be useful in monitoring tumor progression, remission, and recurrence during or after treatment. Moreover, the use of VAF analysis appears to be beneficial in making treatment decisions. However, several issues require better understanding and standardization before VAF testing can be implemented in clinical practice. In this review, we discuss the difficulties in the application of ctDNA VAF analysis in clinical routine, discussing the diagnostic and methodological challenges in VAF measurement in liquid biopsy. We highlight the possible applications of VAF-based measurements that are under consideration in clinical trials in the monitoring of personalized treatments for patients with NSCLC

Influence of Environmental Factors and Relationships between Vanadium, Chromium, and Calcium in Human Bone

The aim of this study was to investigate the impact of environmental factors on the concentrations of vanadium (V), chromium (Cr), and calcium (Ca) and to examine the synergistic or antagonistic relationships between these metals, in cartilage (C), cortical bone (CB), and spongy bone (SB) samples obtained following hip joint surgery on patients with osteoarthritis in NW Poland. We found significantly higher concentrations of V and Cr in spongy bone in patients who consumed game meat and also those with prosthetic implants. Chromium levels were significantly lower in patients with kidney diseases. The greatest positive correlations were found between spongy bone V and (i) the amount of consumed beer and (ii) seafood diet. Correlation analysis also showed a significant correlation between Cr levels and seafood diet. To a certain extent these results indicate that the concentrations of V, Cr, and Ca in the human hip joint tissues are connected with occupational exposure, kidney diseases, diet containing game meat, sea food, beer, and the presence of implants. Furthermore, we noted new types of interactions in specific parts of the femoral head. Vanadium may contribute to the lower bone Ca levels, especially in the external parts (cartilage and cortical bone)

Comparative Distribution and In Vitro Activities of the Urotensin II-Related Peptides URP1 and URP2 in Zebrafish: Evidence for Their Colocalization in Spinal Cerebrospinal Fluid-Contacting Neurons

International audienceUrotensin II (UII) is an evolutionarily conserved neuropeptide initially isolated from teleost fish on the basis of its smooth muscle-contracting activity. Subsequent studies have demonstrated the occurrence of several UII-related peptides (URPs), such that the UII family is now known to include four paralogue genes called UII, URP, URP1 and URP2. These genes probably arose through the two rounds of whole genome duplication that occurred during early vertebrate evolution. URP has been identified both in tetrapods and teleosts. In contrast, URP1 and URP2 have only been observed in ray-finned and cartilaginous fishes, suggesting that both genes were lost in the tetrapod lineage. In the present study, the distribution of urp1 mRNA compared to urp2 mRNA is reported in the central nervous system of zebrafish. In the spinal cord, urp1 and urp2 mRNAs were mainly colocalized in the same cells. These cells were also shown to be GABAergic and express the gene encoding the polycystic kidney disease 2-like 1 (pkd2l1) channel, indicating that they likely correspond to cerebrospinal fluid-contacting neurons. In the hindbrain, urp1-expressing cells were found in the intermediate reticular formation and the glossopharyngeal-vagal motor nerve nuclei. We also showed that synthetic URP1 and URP2 were able to induce intracellular calcium mobilization in human UII receptor (hUT)-transfected CHO cells with similar potencies (pEC50=7.99 and 7.52, respectively) albeit at slightly lower potencies than human UII and mammalian URP (pEC50=9.44 and 8.61, respectively). The functional redundancy of URP1 and URP2 as well as the colocalization of their mRNAs in the spinal cord suggest the robustness of this peptidic system and its physiological importance in zebrafish

<i>urp1</i> mRNA is found in the caudal part of the hindbrain in adult zebrafish.

<p>Expression of <i>urp1</i> revealed by fluorescent ISH (FITC, green) on coronal sections of adult brain <b>(A)</b>. <i>urp1</i> mRNA is visible in neurons located in the intermediate reticular formation <b>(A1</b>) and the region of the glossopharyngeal-vagal motor nerve nuclei (<b>A2–A3</b>). More caudally, at the level of the junction between hindbrain and spinal cord, <i>urp1</i> mRNA occurs at the ventral edge of the central canal <b>(A4)</b>. Schematic sagittal view of an adult zebrafish brain depicting the distribution of <i>urp1</i> mRNA (red dots). Levels of sections shown in A are indicated. The anatomical structures are designated according to [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119290#pone.0119290.ref038" target="_blank">38</a>] <b>(B)</b>. CC, cerebellar crest; C, central canal; CCe, corpus cerebelli; DON, dorsal octavolateralis nucleus; EW, Edinger-Westphal nucleus; FLo, facial lobe; Ha, habenula; H, hypothalamus; IMRF, intermediate reticular formation; MO, medulla oblongata; NC, commissural nucleus of Cajal; nIX-X, glossopharyngeal-vagal motor nerve nuclei; OB, olfactive bulbs; OC, optic chiasma; P, pallium; PN, preopic nucleus; RV, rhombencephalic ventricle; SCsm, spinal cord somatomotor neurons; SP, subpallium; T, thalamus; TO, tectum opticum; TL, torus longitudinalis; TP, posterior tuberculum; TS, torus semicircularis; VLo, vagal lobe. Scale bars: 100 μm.</p

<i>urp1</i>⁺ cells in the hindbrain are cholinergic neurons expressing ChAT in adult zebrafish.

<p><i>urp1</i> expression revealed by fluorescent ISH (TAMRA, red) on coronal sections of adult brain, together with a fluorescent immunostaining for ChAT (Alexa 488, green). <i>urp1</i>⁺ cells express ChAT. Scale bars: 100 μm.</p

<i>urp1</i> mRNA occurs in cells located along the ventral edge of the central canal of spinal cord in adult zebrafish.

<p>Expression of <i>urp1</i> revealed by ISH (BM purple, violet) on free-floating sections of adult spinal cord. <i>urp1</i>⁺ cells form a quasi-continuous line at the ventral edge of the central canal <b>(A)</b>. <i>urp1</i>⁺ cells are in close contact to the lumen of the central canal (arrowhead) <b>(B)</b>. <b>A1</b> and <b>A2</b>, lateral sections with dorsal up; <b>B</b>, coronal section with dorsal up. <i>urp1</i>⁺ cells boxed in <b>A1</b> are shown in <b>A2</b> at higher magnification. M, melanocytes. Scale bars: 50 μm.</p