Summary Background We aimed to assess the efficacy of the oral live attenuated human rotavirus vaccine Rotarix (RIX4414) for prevention of rotavirus gastroenteritis in European infants during their ...first 2 years of life. Methods 3994 study participants were enrolled from six countries and were randomly assigned two oral doses of either RIX4414 (n=2646) or placebo (n=1348), which were coadministered with the first two doses of specific childhood vaccinations. Follow-up for gastroenteritis episodes was undertaken from 2 weeks post-dose two through the two consecutive rotavirus seasons following vaccinations (combined efficacy follow-up period; mean duration 17 months SD 1·6). Our primary endpoint was vaccine efficacy against rotavirus gastroenteritis of any severity during the first efficacy follow-up period (2 weeks post-dose two to the end of the first rotavirus season). Stool specimens obtained during gastroenteritis episodes were tested for rotavirus by ELISA and typed by RT-PCR. Episodes scoring 11 or greater on the 20-point Vesikari scale were classified as severe. Analysis was according to protocol. This study is registered with ClinicalTrials.gov , number NCT00140686 (eTrack102247). Findings 120 infants were excluded from the according-to-protocol analysis. During the first efficacy follow-up period (mean duration 5·7 months SD 1·2), 24 of 2572 infants allocated RIX4414 versus 94 of 1302 given placebo had rotavirus gastroenteritis episodes of any severity, resulting in a vaccine efficacy of 87·1% (95% CI 79·6–92·1; p<0·0001). For the combined efficacy follow-up period, vaccine efficacy against severe rotavirus gastroenteritis was 90·4% (85·1–94·1; p<0·0001), for admission owing to rotavirus gastroenteritis 96·0% (83·8–99·5; p<0·0001), and for rotavirus-related medical attention 83·8% (76·8–88·9; p<0.0001), and significant protection against severe rotavirus gastroenteritis by circulating G1, G2, G3, G4, and G9 rotavirus types was shown. Interpretation In a European setting, two doses of RIX4414 coadministered with childhood vaccines provided high protection against any and severe rotavirus gastroenteritis, with an overall reduction of admissions for gastroenteritis over two consecutive rotavirus epidemic seasons.
Short-pulse metrology and dynamic studies in the extreme ultraviolet (XUV) spectral range greatly benefit from interferometric measurements. In this contribution a Michelson-type all-reflective ...split-and-delay autocorrelator operating in a quasi amplitude splitting mode is presented. The autocorrelator works under a grazing incidence angle in a broad spectral range (10 nm – 1
μ
m) providing collinear propagation of both pulse replicas and thus a constant phase difference across the beam profile. The compact instrument allows for XUV pulse autocorrelation measurements in the time domain with a single-digit attosecond precision and a useful scan length of about 1 ps enabling a decent resolution of E/ΔE = 2000 at 26.6 eV. Its performance for selected spectroscopic applications requiring moderate resolution at short wavelengths is demonstrated by characterizing a sharp electronic transition at 26.6 eV in Ar gas. The absorption of the 11
th
harmonic of a frequency-doubled Yb-fiber laser leads to the well-known 3s3p
6
4p
1
P
1
Fano resonance of Ar atoms. We benchmark our time-domain interferometry results with a high-resolution XUV grating spectrometer and find an excellent agreement. The common-path interferometer opens up new opportunities for short-wavelength femtosecond and attosecond pulse metrology and dynamic studies on extreme time scales in various research fields.
Plasminogen deficiency SCHUSTER, V.; HÜGLE, B.; TEFS, K.
Journal of thrombosis and haemostasis,
December 2007, 2007-Dec, 2007-12-00, 20071201, Letnik:
5, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Plasminogen (plg) deficiency has been classified as (i) hypoplasminogenemia or ‘true’ type I plg deficiency, and (ii) dysplasminogenemia, also called type II plg deficiency. Both forms, severe ...hypoplasminogenemia and dysplasminogenemia, are not causally linked to venous thrombosis. Dysplasminogenemia does not lead to a specific clinical manifestation and probably represents only a polymorphic variation in the general population, mainly in Asian countries. Severe hypoplasminogenemia is associated with compromised extracellular fibrin clearance during wound healing, leading to pseudomembraneous (ligneous) lesions on affected mucous membranes (eye, middle ear, mouth, pharynx, duodenum, upper and lower respiratory tract and female genital tract). Ligneous conjunctivitis is by far the most common clinical manifestation. More than 12% of patients with severe hypoplasminogenemia exhibit congenital occlusive hydrocephalus. In milder cases of ligneous conjunctivitis, topical application of plg‐containing eye drops, fresh frozen plasma, heparin, corticosteroids or certain immunosuppressive agents (such as azathioprine) may be more or less effective. Oral treatment with sex hormones was successful in two female patients with ligneous conjunctivitis. In severe cases with possibly life‐threatening multi‐organ involvement, true therapeutic options are not available at present. The plg‐knockout mouse is a useful tool to study the many different properties of plg in a variety of settings, such as wound healing, tissue repair and tissue remodeling, virulence and invasiveness of certain bacteria in the human host, tumor growth and dissemination, as well as arteriosclerosis.
The synthesis of a series of coumarin-based chemosensor assemblies for zinc is detailed, using established and novel synthetic pathways. Variations of the nature of the chelating unit (DPA or ...cyclen), position of the attachment point of the chelating unit (3- or 4-position), and nature of the 7-substituent (−OH, −OAc, or −NR2) on the coumarin play a crucial role in whether, and to what extent, a CHEF-type or ratiometric response of the chemosensor is observed. Solvent effects are also discussed. The chemosensors were shown to be competent for detecting zinc pools in cultured rat pituitary (GH3) and hepatoma (H4IIE) cell lines. The work further defines the design algorithms for zinc-selective CHEF-type and ratiometric chemosensors.
The issues of improving the efficiency of processing the results of studying the reservoir filtration properties (RFP) within the oil-and gas-producing areas of the central part of the West Siberian ...petroleum province are considered. The high degree of development of the hydrocarbon resources of the studied area is determined by the presence of deposits that developed for a long period of time. It enables one to solve tasks aimed at increasing the efficiency of searching for complex deeply buried reservoirs, as well as the efficiency of their exploration and additional exploration, since the overlying productive horizons are practically developed. This task is considered one of the most important at the current stage of field development in this region due to the decline in oil production at the main large fields and is open to interpretation. The present paper covers the issues of reservoir modeling using new scientific and methodological approaches to geophysical data processing and the possibility of using modern software products when grouping development objects according to criteria corresponding to a reservoir of a certain lithotype. This approach allowed us to develop high-quality geological models and justify the use of the most effective complex of geophysical studies for modeling low-amplitude (no more than 15 m) and small(less than 20 km
2
) oil deposits. In the course of research the results of studying the reservoir filtration properties were processed; low-amplitude and small deposits of channel sediments (river valleys) were established, the commercial oil and gas content of complex sediments characterized by low-amplitude and small deposits (Tyumen Formation, Yu
2
reservoir) was proved, the results of geophysical exploration (GIS) in wells were interpreted, the GIS results were compared with the energy characteristics of the reflected waves (seismic studies), zones saturated with water-oil-gas fluids were established (3D models were developed), and the possibility of using this technique for identifying and mapping complex deep oil deposits was shown.
This paper reports on the issues on the study of the lithological and petrographic composition and formation of oil occurrences within the fields of the Surgut Dome and the Frolov Megabasin. It has ...been revealed that the formation of the oil occurrences of the sedimentary cover is associated with the peculiarities of the geological structure and the oil-bearing capacity of the basement rocks. In the study area, a high level of oil-bearing sedimentary cover is observed within the central part of the Surgut Dome. The Pre-Jurassic part of the section can have additional sources of intensification of hydrocarbons in the Lower–Middle Jurassic deposits. The presence of deep fault zones is the search criterion for the detection of secondary reservoirs in them, both in the destruction zones, basement, and in the Lower–Middle Jurassic deposits. Therefore, fields can be formed due to deep fluids vertically ascending through faults that cross the basement and the sedimentary cover. This paper also reports on the potential oil and gas bearing capacity of the Lower–Middle Jurassic deposits. In this regard, study of granitoid massifs, the degree of detail in distinguishing sedimentation conditions, and establishment of contact zones between the sedimentary cover and underlying formations have to be considered.
The World Health Organization (WHO), the European Technical Advisory Group of Experts on Immunisation (ETAGE) and the European Society for Paediatric Infectious Diseases/European Society for ...Paediatric Gastroenterology, Hepatology, and Nutrition (ESPID/ESPGHAN) have also recommended universal RV immunisation of healthy infants, in parallel with ensuring that adequate measures are taken to attain high vaccination coverage and timely administration of each dose 8-10. Western Europe Introduction of RV UMV in Europe has been relatively slow compared with the Americas, with only Austria, Belgium, Finland, Luxembourg (and - outside of Europe proper - Israel) having introduced RV UMV by 2012.\n Furthermore, introduction of RV UMV has resulted in a decrease in the incidence of and a delay in the yearly peak of RVGE in many settings. ...positive updates on safety issues pertaining to the presence of PCV and risk of IS or Kawasaki disease have allayed some concerns regarding RV vaccines in the wider community, and vaccine impact and effectiveness studies will form an increasingly important strand of evidence to support the widening of RV UMV, both in Europe and elsewhere.
Many in-vitro experiments performed to study the response of thiol-containing proteins to changes in environmental redox potentials use dithiothreitol (DTT) to maintain a preset redox environment ...throughout the experiments. However, the gradual oxidation of DTT during the course of the experiments, and the interaction between DTT and other components in the system, can significantly alter the initial redox potential and complicate data interpretation. Having an internal reporter of the actual redox potential of the assayed sample facilitates direct correlation of biochemical findings with experimental redox status. Reversed-phase high-performance liquid chromatography (RP-HPLC) is a widely used, well-established tool for analysis and purification of biomolecules, including proteins and peptides. Here, we describe a simple, robust, and quantitative RP-HPLC method we developed and tested for determination of the experimental redox potential of an in-vitro sample at the time of the experiment. It exploits the specific UV-absorbance of the oxidized intrinsic DTT in the samples and retains the high resolving power and high sensitivity of RP-HPLC with UV detection.
Abstract Background Efforts to reduce the impact of group A rotaviruses on human morbidity and mortality rely on oral immunisation with live attenuated or recombinant vaccines. A major challenge in ...immunisation is the vast inter- and intragenotypic diversity accomplished by circulating rotaviruses. Objectives To monitor rotavirus inter- and intragenotypic diversity in hospitalised children. Study design From January 2008 to December 2009 stool samples from 1994 paediatric in-patients suffering from diarrhoea were screened for rotavirus. Rotavirus G- and P-genotypes were determined by nucleotide sequencing and phylogenetic analysis was performed. Results Rotavirus A was detected in stool samples of 341 children, comprising G1P8, G2P4, G3P8, G4P8, G9P8, as well as uncommon G12P6 genotypes and mixed infections. Predominant strains shifted from G1P8 and G9P8 genotypes in the first season to G3P8 and G4P8 genotypes in the second season. The highest intragenotypic diversity was detected in G1 strains and consisted of co-circulating G1-Ic, G1-Id, G1-Ie and G1-II rotaviruses. The G2 analysis revealed different intragenotypic lineages: G2-IIa, G2-IIb and G2-IIc. Interestingly, the circulating G4-Ib rotaviruses were characterised by insertions of 3 or 6 additional coding nucleotides within variable region 4 of VP7. Whereas different G9-III VP7 gene segments were detected G3-Ia sequences were highly homologous. In the VP4 analysis P8-III gene segment predominated over P4-Vb, P8-I, P8-IV and P6-I. Conclusions A remarkable rotavirus heterogeneity was detected in the limited local setting and time span. Continued monitoring and nucleotide sequencing is necessary to document possible effects of rising immunisation levels on intragenotypic rotavirus diversity.