Warfarin pharmacogenomic testing has become a prime example of the utility of personalized molecular testing in the modern clinical laboratory. Warfarin is a commonly used drug for the prevention and ...treatment of thromboembolic complications in a variety of clinical situations. However, a number of factors lead to a high interindividual variability in dose requirements. Among the primary factors in this variability are genetic polymorphisms in general patient populations, which can account for 35-50% of varying dose requirements among patients. In this review, we discuss the implications of polymorphisms in the cytochrome P-450 enzyme 2C9 (CYP2C9) and Vitamin K Epoxide Reductase Enzyme Complex subunit 1 (VKORC1) as they relate to therapeutic warfarin dosing. We discuss the clinical utility of pharmacogenomics testing as related to warfarin dosing, and propose a clinical model for the implementation of the pharmacogenomic test results. Finally, we provide a brief overview of the currently available commercial testing platforms with discussion of the complexities of utilizing patented methodologies in bringing genetic testing such as this to the clinical laboratory.
The influence of steroids on the antibody response to a MF59-adjuvanted influenza vaccine in elderly COPD patients has not been studied previously.
In the influenza season 2001/02 (October–February) ...elderly COPD patients were recruited at 14 doctor's offices and our 250-bed hospital. Patients were stratified into three groups according to current treatment regimen: (a) >10
mg of prednisolone/day (SS); (b) inhaled steroids (IS); (c) no steroid treatment (control group, CG). All patients were vaccinated with the MF59-adjuvanted influenza vaccine. Antibodies against the influenza strains A/H1N1, A/H3N2, and B were measured at baseline, 4 and 24 weeks after vaccination by hemagglutination inhibition (HI) assay.
One-hundred and sixty-two patients completed the study (CG
n
=
42; IS
n
=
87; SS
n
=
33). Mean age was 71.3 years (range 60–89). Twenty-one percent of all patients reported local reactions; no serious adverse events were observed. Four weeks after vaccination, mean geometric HI titres (GMT) for A/H1N1, A/H3N and B increased significantly in all groups (
p
≤
0.05). After 24 weeks, GMTs to A/H1N1 and A/H3N2 returned to baseline, while GMTs to type B remained significantly higher than baseline in all groups. Significant differences between the groups as regards GMTs, seroconversion (56–89%) or seroprotection rates (64–93%) were not observed.
Systemic steroids did not influence the antibody response towards the MF59-adjuvanted influenza vaccine. We found that the strains included in the vaccine showed varying long-term immunogenicity.
Four novel U(VI) containing coordination polymers, UO2(C7H10O4) (1), UO2(C8H12O4) (2), UO2(C9H14O4) (3), and UO2(C10H16O4) (4), were synthesized from UO2(NO3)2·6H2O and aliphatic dicarboxylic acids ...(pimelic, suberic, azelaic, and sebacic acids, respectively) using hydrothermal techniques and were characterized by single-crystal diffraction. Compounds 1 and 4 consist of (UO2)2O8 dimers connected by the acid molecules to form layers, whereas 2 and 3 are constructed of chains of hexagonal bipyramids connected to form layers. These materials complete the series of aliphatic uranyl carboxylates to C10 (sebacic acid) and may be considered to be carboxylate “end-members” of a series of dipyridyl/carboxylate structures described in part II of this investigation (following in this issue).
The extent of the H1N1 pandemic has been estimated from case counts and deaths but the proportion of exposed populations with inapparent infections has not been described in detail. We analysed ...haemagglutination-inhibition (HI) antibody titres of pre-vaccination sera from pandemic vaccine trials conducted in six countries on four continents to provide an indication of A/CA/07/2009(H1N1)-like influenza seroprevalence in those populations. Among 7,962 subjects, ranging in age from 12 months to over 60 years, the proportions with HI antibody titres > or =40 to the H1N1pnd virus in the period from August to October 2009 were, by country: Costa Rica 26.4%, United States (US) 22.5%, Switzerland 16.9%, Germany 12.6%, Belgium 10.1%, and Japan 5.9%. Age-specific seropositivity rates in the samples were higher in children and adolescents in Costa Rica and in the US than in Europe and in Japan. The low proportion of seropositive children in Europe and Japan suggests that little local viral transmission had occurred in those regions even as late as September and October 2009, while in the US and Costa Rica, the greater proportion of previously infected children and young adults suggested that a significant number of asymptomatic infections had occurred during the first pandemic wave. Nevertheless, in all locations, the majority of the population remained susceptible to the pandemic virus at the beginning of the influenza season in the northern hemisphere, justifying the implementation of public health interventions.
A human BK-2 bradykinin receptor was cloned from the lung fibroblast cell line CCD-16Lu. The cDNA clone encodes a 364 amino acid protein that has the characteristics of a seven transmembrane domain ...G-protein coupled receptor. The predicted amino acid sequence of the human BK-2 receptor is 81% identical to the smooth muscle rat BK-2 receptor (1). Transfection of the human BK-2 receptor cDNA into COS-7 cells results in the expression of high levels of specific BK binding sites. Saturation binding analysis indicates that the human BK-2 receptor expressed in COS-7 cells binds BK with a KD of 0.13 nM. Pharmacological characterization of the expressed BK receptor is consistent with the cDNA encoding a receptor of the BK-2 subtype. The BK-2 receptor antagonist Hoe 140 (2), D-Arg0Hyp3, Thi5, D-Tic7, Oic8BK has a high affinity (IC50 = 65 pM) for the cloned human receptor. The tissue distribution of the human BK-2 receptor was analyzed by competitive PCR with human tissue cDNA and is similar to that determined for the BK-2 receptor in the rat.
Recently, it can be observed a growing interest in 3D building or city models created from laser scanning data. These models are used in many areas of interest. In this work the accuracy assessment ...of 3D buildings models created from airborne and terrestrial laser scanning data was carried out. TLS data for modelling were acquired with average point spacing about 0.02 m. In order to model invisible from the ground building elements such as roofs, the LIDAR data was used with density of about 12 pts./m2. TLS and LIDAR data were acquired in the same coordinates system. For textures mapping a set of 10 Mpix digital images using SLR camera Canon 40D were taken. Modelling was performed using both commercial software Leica Cyclone, as well as original software and free software. The accuracy of models is affected by many factors, but the impact of all factors leading to errors of the final models were analysed together. The accuracy of models was assessed by comparing the coordinates of characteristic points of the models and the corresponding coordinates of these points measured on real buildings. The accuracy of points measured on the real building was not affected by model errors, therefore they can be treated as error-free reference points. On site reference measurements were performed using Leica TCR407Power reflectorless total station. Obtained inaccuracies of the reconstructed models were as follow: 0.12 m horizontal, 0.1 3m vertical, 0.18 m three-dimensional.
In recent years, much attention has been devoted to digital elevation models (DEMs) produced using Synthetic Aperture Radar Interferometry (InSAR). This has been triggered by the relative novelty of ...the InSAR method and its world-famous product—the Shuttle Radar Topography Mission (SRTM) DEM. However, much less attention, if at all, has been paid to sources of artefacts in SRTM. In this work, we focus not on the missing pixels (null pixels) due to shadows or the layover effect, but rather on outliers that were undetected by the SRTM validation process. The aim of this study is to identify some of the causes of the elevation outliers in SRTM. Such knowledge may be helpful to mitigate similar problems in future InSAR DEMs, notably the ones currently being developed from data acquired by the TanDEM-X mission. We analysed many cross-sections derived from SRTM. These cross-sections were extracted over the elevation test areas, which are available from the Global Elevation Data Testing Facility (GEDTF) whose database contains about 8,500 runways with known vertical profiles. Whenever a significant discrepancy between the known runway profile and the SRTM cross-section was detected, a visual interpretation of the high-resolution satellite image was carried out to identify the objects causing the irregularities. A distance and a bearing from the outlier to the object were recorded. Moreover, we considered the SRTM look direction parameter. A comprehensive analysis of the acquired data allows us to establish that large metallic structures, such as hangars or car parking lots, are causing the outliers. Water areas or plain wet terrains may also cause an InSAR outlier. The look direction and the depression angle of the InSAR system in relation to the suspected objects influence the magnitude of the outliers. We hope that these findings will be helpful in designing the error detection routines of future InSAR or, in fact, any microwave aerial- or space-based survey. The presence of outliers in SRTM was first reported in Becek, K. (2008). Investigating error structure of shuttle radar topography mission elevation data product, Geophys. Res. Lett., 35, L15403.
High‐pressure and high‐temperature behavior of synthetic Ni2P has been studied in a laser‐heated diamond anvil cell up to 50 GPa and 2200 K. Incongruent melting associated with formation of ...pyrite‐type NiP2 and amorphous Ni‐P alloy was found at an intermediate pressure range, between 6.5 and 40 GPa. Above 40 GPa, Ni2P melts congruently. At room conditions, Ni2P has hexagonal C22‐type structure, and without heating it remains in this structure to at least 50 GPa. With a bulk modulus K0 = 201(8) GPa and K' = 4.2(6), Ni2P is noticeably less compressible than hcp Fe, as well as all previously described iron phosphides, and its presence in the Earth core would favorably lower the core density. In contrast to Fe2P, the c/a ratio in Ni2P decreases on compression because of the lack of ferromagnetic interaction along the c direction. Lack of the C22→C23 transition in Ni2P rules out a stabilizing effect of Ni on the orthorhombic phase of natural (Fe1−xNix)2P allabogdanite.
Loss of expression or mutational deletion of the cyclin-dependent kinase inhibitor p27(Kip1) has recently been implicated
in malignant development. In this study, we investigated the relationship ...between p27(Kip1) protein expression and tumor grade
in human prostate cancer by conducting an immunohistochemical analysis in a series of normal prostate, benign prostatic hyperplasia,
and malignant prostate cancer specimens. The proliferative activity of prostatic tumors was determined on the basis of the
Ki-67 nuclear antigen staining. A uniformly intense immunoreactivity for p27(Kip1) was localized to the nuclei of glandular
epithelial cells of normal prostates. The benign glandular epithelia exhibited moderate immunostaining. In the malignant prostate
tissue, however, a heterogeneous pattern of substantially reduced p27(Kip1) immunoreactivity was found among the glandular
epithelial cells. The majority of primary prostate cancer specimens (68%) were totally negative for p27(Kip1) immunoreactivity,
whereas the rest exhibited a significantly decreased p27(Kip1) expression, compared with the normal prostate (P < 0.01). Moreover,
there was progressively diminished p27(Kip1) immunostaining with increased tumor grade. This loss of p27(Kip1) was associated
with an increase in the proliferative index of prostatic tumors (r = 0.88). There was no significant relationship between
p27(Kip) loss and the transforming growth factor beta receptor status of prostatic adenocarcinomas. These results indicate
that frequent loss of the cyclin-dependent kinase inhibitor p27(Kip1) in human prostate cancer cells correlates with advancing
histological aggressiveness, implicating deregulation of p27(Kip1) in prostate tumor progression.
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