Ionospheric effects on one-way timing signals

A proposed navigation concept requires that a user measure the time-delay that satellite-emitted signals experience in traversing the distance between satellite and user. Simultaneous measurement of the propagation time from four different satellites permits the user to determine his position and clock bias if satellite ephemerides and signal propagation velocity are known. A pulse propagating through the ionosphere is slowed down somewhat, giving an apparent range that is larger than the equivalent free space range. The difference between the apparent range and the true range, or the free space velocity and the true velocity, is the quantity of interest. This quantity is directly proportional to the total electron content along the path of the propagating signal. Thus, if the total electron content is known, or is measured, a perfect correction to ranging could be performed. Faraday polarization measurements are continuously being taken at Fort Monmouth, N. J., using beacon emissions of the ATS-3 (137.35 MHz) satellite. Day-to-day variability of the diurnal variation of total electron content values is present with differences of up to 50% or more not being uncommon. In addition, superposed on the overall diurnal variation are smaller scale variations of approximately 5 to 10% of the total content which are attributed to ionospheric density irregularities

Plasmaspheric effects on one way satellite timing signals

The effects of the ionospheric retardation of satellite-emitted timing signals was presented. The retardation at the navigation frequencies, which is proportional to the total ionospheric electron content (TEC), was determined by Faraday polarization measurements of VHF emissions of a geostationary satellite. The polarization data yielded TEC up to approximately 1200 km only, since the measurement technique is based on the Faraday effect which is weighted by the terrestrial magnetic field

The Pediatrician and Disaster Preparedness

Recent natural disasters and events of terrorism and war have heightened society's recognition of the need for emergency preparedness. In addition to the unique pediatric issues involved in general emergency preparedness, several additional issues related to terrorism preparedness must be considered, including the unique vulnerabilities of children to various agents as well as the limited availability of age- and weight-appropriate antidotes and treatments. Although children may respond more rapidly to therapeutic intervention, they are at the same time more susceptible to various agents and conditions and more likely to deteriorate if not monitored carefully.The challenge of dealing with the threat of terrorism, natural disasters, and public health emergencies in the United States is daunting not only for disaster planners but also for our medical system and health professionals of all types, including pediatricians. As part of the network of health responders, pediatricians need to be able to answer concerns of patients and families, recognize signs of possible exposure to a weapon of terror, understand first-line response to such attacks, and sufficiently participate in disaster planning to ensure that the unique needs of children are addressed satisfactorily in the overall process. Pediatricians play a central role in disaster and terrorism preparedness with families, children, and their communities. This applies not only to the general pediatrician but also to the pediatric medical subspecialist and pediatric surgical specialist. Families view pediatricians as their expert resource, and most of them expect the pediatrician to be knowledgeable in areas of concern. Providing expert guidance entails educating families in anticipation of events and responding to questions during and after actual events. It is essential that pediatricians educate themselves regarding these issues of emergency preparedness. For pediatricians, some information is currently available on virtually all of these issues in recently produced printed materials, at special conferences, in broadcasts of various types, and on the Internet. However, selecting appropriate, accurate sources of information and determining how much information is sufficient remain difficult challenges. Similarly, guidance is needed with respect to developing relevant curricula for medical students and postdoctoral clinical trainees

Structural and micro-anatomical changes in vertebrae associated with idiopathic-type spinal curvature in the curveback guppy model

Background: The curveback lineage of guppy is characterized by heritable idiopathic-type spinal curvature thatdevelops during growth. Prior work has revealed several important developmental similarities to the human idiopathicscoliosis (IS) syndrome. In this study we investigate structural and histological aspects of the vertebrae that areassociated with spinal curvature in the curveback guppy and test for sexual dimorphism that might explain a femalebias for severe curve magnitudes in the population.Methods: Vertebrae were studied from whole-mount skeletal specimens of curved and non-curved adult males andfemales. A series of ratios were used to characterize structural aspects of each vertebra. A three-way analysis of variancetested for effects of sex, curvature, vertebral position along the spine, and all 2-way interactions (i.e., sex and curvature,sex and vertebra position, and vertebra position and curvature). Histological analyses were used to characterize microarchitecturalchanges in affected vertebrae and the intervertebral region.Results: In curveback, vertebrae that are associated with curvature demonstrate asymmetric shape distortion,migration of the intervertebral ligament, and vertebral thickening on the concave side of curvature. There is sexualdimorphism among curved individuals such that for several vertebrae, females have more slender vertebrae than domales. Also, in the region of the spine where lordosis typically occurs, curved and non-curved females have a reducedwidth at the middle of their vertebrae, relative to males.Conclusions: Based on similarities to human spinal curvatures and to animals with induced curves, the concaveconvexbiases described in the guppy suggest that there is a mechanical component to curve pathogenesis incurveback. Because idiopathic-type curvature in curveback is primarily a sagittal deformity, it is structurally more similarto Scheuermann kyphosis than IS. Anatomical differences between teleosts and humans make direct biomechanicalcomparisons difficult. However, study of basic biological systems involved in idiopathic-type spinal curvature incurveback may provide insight into the relationship between a predisposing aetiology, growth, and biomechanics.Further work is needed to clarify whether observed sex differences in vertebral characteristics are related to the femalebias for severe curves that is observed in the population

Critical Early Roles for col27a1a and col27a1b in Zebrafish Notochord Morphogenesis, Vertebral Mineralization and Post-embryonic Axial Growth

Fibrillar collagens are well known for their links to human diseases, with which all have been associated except for the two most recently identified fibrillar collagens, type XXIV collagen and type XXVII collagen. To assess functions and potential disease phenotypes of type XXVII collagen, we examined its roles in zebrafish embryonic and post-embryonic development.We identified two type XXVII collagen genes in zebrafish, col27a1a and col27a1b. Both col27a1a and col27a1b were expressed in notochord and cartilage in the embryo and early larva. To determine sites of type XXVII collagen function, col27a1a and col27a1b were knocked down using morpholino antisense oligonucleotides. Knockdown of col27a1a singly or in conjunction with col27a1b resulted in curvature of the notochord at early stages and formation of scoliotic curves as well as dysmorphic vertebrae at later stages. These defects were accompanied by abnormal distributions of cells and protein localization in the notochord, as visualized by transmission electron microscopy, as well as delayed vertebral mineralization as detected histologically.Together, our findings indicate a key role for type XXVII collagen in notochord morphogenesis and axial skeletogenesis and suggest a possible human disease phenotype

Comparative efficacy and safety of biosimilar infliximab and other biological treatments in ankylosing spondylitis: systematic literature review and meta-analysis.

OBJECTIVES: To compare the efficacy and safety of infliximab-biosimilar with other biological drugs for the treatment of active ankylosing spondylitis (AS). METHODS: Systematic literature review for randomized controlled trials (RCTs) with adalimumab, etanercept, golimumab, infliximab and infliximab-biosimilar in AS was performed and indirect meta-analysis (Bayesian mixed treatment comparison) was carried out. The proportion of patients reaching 20 % improvement by the assessment of Spondyloarthritis International Society response criteria (ASAS20) at weeks 12 and 24 was used as efficacy endpoints, and the occurrence of serious adverse events at week 24 was applied to compare the safety of the biologicals. RESULTS: Altogether, 13 RCTs, identified by the systematic literature search, were included in the analysis. Results on the ASAS20 efficacy endpoint were reported for week 12 in 12 RCTs involving 2,395 patients, and for week 24 in 5 RCTs comprising 1,337 patients. All the five biological agents proved to be significantly superior to placebo. Infliximab showed the highest odds ratio (OR) of 7.2 (95 % CI 3.68-13.19) compared to placebo, followed by infliximab-biosimilar with OR 6.25 (95 % CI 2.55-13.14), both assessed at week 24. No significant difference was found between infliximab-biosimilar and other biological treatments regarding their efficacy and safety. CONCLUSIONS: This is the first study which includes a biosimilar drug in the meta-analysis of biological treatments in AS. The results have proven the similar efficacy and safety profile of infliximab-biosimilar treatment compared to other biologicals

Enhancement of carotenoids biosynthesis in Chlamydomonas reinhardtii by nuclear transformation using a phytoene synthase gene isolated from Chlorella zofingiensis

The isolation and characterization of the phytoene synthase gene from the green microalga Chlorella zofingiensis (CzPSY), involved in the first step of the carotenoids biosynthetic pathway, have been performed. CzPSY gene encodes a polypeptide of 420 amino acids. A single copy of CzPSY has been found in C. zofingiensis by Southern blot analysis. Heterologous genetic complementation in Escherichia coli showed the ability of the predicted protein to catalyze the condensation of two molecules of geranylgeranyl pyrophosphate (GGPP) to form phytoene. Phylogenetic analysis has shown that the deduced protein forms a cluster with the rest of the phytoene synthases (PSY) of the chlorophycean microalgae studied, being very closely related to PSY of plants. This new isolated gene has been adequately inserted in a vector and expressed in Chlamydomonas reinhardtii. The overexpression of CzPSY in C. reinhardtii, by nuclear transformation, has led to an increase in the corresponding CzPSY transcript level as well as in the content of the carotenoids violaxanthin and lutein which were 2.0- and 2.2-fold higher than in untransformed cells. This is an example of manipulation of the carotenogenic pathway in eukaryotic microalgae, which can open up the possibility of enhancing the productivity of commercial carotenoids by molecular engineering

False-negative PD-L1 immunostaining in ethanol-fixed EBUS-TBNA specimens of non-small cell lung cancer patients

Aims Programmed death-ligand 1 (PD-L1) immunostaining is used to predict which non-small-cell lung cancer (NSCLC) patients will respond best to treatment with programmed cell death protein 1/PD-L1 inhibitors. PD-L1 immunostaining is sometimes performed on alcohol-fixed cytological specimens instead of on formalin-fixed paraffin-embedded (FFPE) biopsies or resections. We studied whether ethanol prefixation of clots from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) results in diminished PD-L1 immunostaining as compared with formalin fixation. Methods and results FFPE cell blocks from EBUS-TBNA specimens of 54 NSCLC patients were identified. For each case, paired samples were available, consisting of clots directly immersed in formalin and clots prefixed in Fixcyt (50% ethanol). Serial sections were immunostained for PD-L1 by use of the standardised SP263 assay and the 22C3 antibody as a laboratory-developed test (LDT). PD-L1 positivity was determined with two cut-offs (1% and 50%). Concordance of PD-L1 positivity between the formalin-fixed (gold standard) and ethanol-prefixed material was assessed. When the 22C3 LDT was used, 30% and 36% of the ethanol-prefixed specimens showed false-negative results at the 1% and 50% cut-offs, respectively (kappa 0.64 and 0.68). When SP263 was used, 22% of the ethanol-prefixed specimens showed false-negative results at the 1% cut-off (kappa 0.67). At the 50% cut-off, concordance was higher (kappa 0.91), with 12% of the ethanol-prefixed specimens showing false-negative results. Conclusion Ethanol fixation of EBUS-TBNA specimens prior to formalin fixation can result in a considerable number of false-negative PD-L1 immunostaining results when a 1% cut-off is used and immunostaining is performed with SP263 or the 22C3 LDT. The same applies to use of the 50% cut-off when immunostaining is performed with the 22C3 LDT