The reference surveillance method in patients with Barrett's esophagus is careful endoscopic observation, with targeted as well as random four-quadrant biopsies. Autofluorescence endoscopy (AFE) may ...make it easier to locate neoplasia. The aim of this study was to elucidate the diagnostic accuracy of surveillance with AFE-guided plus four-quadrant biopsies in comparison with the conventional approach.
A total of 187 of 200 consecutive Barrett's esophagus patients who were initially enrolled (73 % male, mean age 67 years, mean Barrett's segment length 4.6 cm), who underwent endoscopy for Barrett's esophagus in four study centers, were randomly assigned to undergo either AFE-targeted biopsy followed by four-quadrant biopsies or conventional endoscopic surveillance, also including four-quadrant biopsies (study phase 1). After exclusion of patients with early cancer or high-grade dysplasia, who underwent endoscopic or surgical treatment, as well as those who declined to participate in phase 2 of the study, 130 patients remained. These patients were examined again with the alternative method after a mean of 10 weeks, using the same methods described. The main study parameter was the detection of early cancer/adenocarcinoma or high-grade dysplasia (HGD), comparing both approaches in study phase 1; the secondary study aim in phase 2 was to assess the additional value of the AFE-guided approach after conventional surveillance, and vice versa. Test accuracy measures were derived from study phase 1.
In study phase 1, the AFE and conventional approaches yielded adenocarcinoma/HGD rates of 12 % and 5.3 %, respectively, on a per-patient basis. With AFE, four previously unrecognized adenocarcinoma/HGD lesions were identified (4.3 % of the patients); with the conventional approach, one new lesion (1.1 %) was identified. Of the 19 adenocarcinoma/HGD lesions detected during AFE endoscopy in study phase 1, eight were visualized, while 11 were only detected using untargeted four-quadrant biopsies (sensitivity 42 %). Of the 766 biopsies classified at histology as being nonneoplastic, 58 appeared suspicious (specificity 92 %, positive predictive value 12 %, negative predictive value 98.5 %). In study phase 2, AFE detected two further lesions in addition to the initial alternative approach in 3.2 % of cases, in comparison with one lesion with conventional endoscopy (1.7 %).
In this referral Barrett's esophagus population with a higher prevalence of neoplastic lesions, the AFE-guided approach improved the diagnostic yield for neoplasia in comparison with the conventional approach using four-quadrant biopsies. However, AFE alone was not suitable for replacing the standard four-quadrant biopsy protocol.
Background
Approximately, 20–30% of patients with gastro‐esophageal reflux disease (GERD) experience persistent symptoms despite treatment with proton pump inhibitors (PPIs). These patients may have ...underlying dysmotility; therefore, targeting gastric motor dysfunction in addition to acid inhibition may represent a new therapeutic avenue. The aim of this study was to assess the pharmacodynamic effect of the prokinetic agent revexepride (a 5‐HT4 receptor agonist) in patients with GERD who have persistent symptoms despite treatment with a PPI.
Methods
This was a phase II, exploratory, multicenter, randomized, placebo‐controlled, double‐blind, parallel‐group study in patients with GERD who experienced persistent symptoms while taking a stable dose of PPIs (ClinicalTrials.gov identifier: NCT01370863). Patients were randomized to either revexepride (0.5 mg, three times daily) or matching placebo for 4 weeks. Reflux events and associated characteristics were assessed by pH/impedance monitoring and disease symptoms were assessed using electronic diaries and questionnaires.
Key Results
In total, 67 patients were enrolled in the study. There were no significant differences between study arms in the number, the mean proximal extent or the bolus clearance times of liquid‐containing reflux events. Changes from baseline in the number of heartburn, regurgitation, and other symptom events were minimal for each treatment group and no clear trends were observed.
Conclusions & Inferences
No clear differences were seen in reflux parameters between the placebo and revexepride groups.
The aim of this study was to assess the pharmacodynamic effect of the prokinetic agent revexepride (a 5‐HT4 receptor agonist) in patients with GERD who have persistent symptoms despite treatment with a PPI. Reflux events and associated characteristics were assessed by pH/impedance monitoring and disease symptoms were assessed using electronic diaries and questionnaires. No clear differences were seen in reflux parameters between the placebo and revexepride groups.
Background:Hepatitis C virus (HCV) infection is associated with decreased health-related quality of life (HRQOL). Although HCV has been suggested to directly impair neuropsychiatric functions, other ...factors may also play a role.Patients and methods:In this cross-sectional study, we assessed the impact of various host-, disease- and virus-related factors on HRQOL in a large, unselected population of anti-HCV-positive subjects. All individuals (n = 1736) enrolled in the Swiss Hepatitis C Cohort Study (SCCS) were asked to complete the Short Form 36 (SF-36) and the Hospital Anxiety Depression Scale (HADS).Results:833 patients (48%) returned the questionnaires. Survey participants had significantly worse scores in both assessment instruments when compared to a general population. By multivariable analysis, reduced HRQOL (mental and physical summary scores of SF-36) was independently associated with income. In addition, a low physical summary score was associated with age and diabetes, whereas a low mental summary score was associated with intravenous drug use. HADS anxiety and depression scores were independently associated with income and intravenous drug use. In addition, HADS depression score was associated with diabetes. None of the SF-36 or HADS scores correlated with either the presence or the level of serum HCV RNA. In particular, SF-36 and HADS scores were comparable in 555 HCV RNA-positive and 262 HCV RNA-negative individuals.Conclusions:Anti-HCV-positive subjects have decreased HRQOL compared to controls. The magnitude of this decrease was clinically important for the SF-36 vitality score. Host and environmental, rather than viral factors, seem to impact on HRQOL level.
We have engineered a class of colloids which can recognize the shape and size of targeted microbial cells and selectively bind to their surfaces. These imprinted colloid particles, which we called ..."colloid antibodies", were fabricated by partial fragmentation of silica shells obtained by templating the targeted microbial cells. We successfully demonstrated the shape and size recognition between such colloidal imprints and matching microbial cells. High percentage of binding events of colloidal imprints with the size matching target particles was achieved. We demonstrated selective binding of colloidal imprints to target microbial cells in a binary mixture of cells of different shapes and sizes, which also resulted in high binding selectivity. We explored the role of the electrostatic interactions between the target cells and their colloid imprints by pre-coating both of them with polyelectrolytes. Selective binding occurred predominantly in the case of opposite surface charges of the colloid cell imprint and the targeted cells. The mechanism of the recognition is based on the amplification of the surface adhesion in the case of shape and size match due to the increased contact area between the target cell and the colloidal imprint. We also tested the selective binding for colloid imprints of particles of fixed shape and varying sizes. The concept of cell recognition by colloid imprints could be used for development of colloid antibodies for shape-selective binding of microbes. Such colloid antibodies could be additionally functionalized with surface groups to enhance their binding efficiency to cells of specific shape and deliver a drug payload directly to their surface or allow them to be manipulated using external fields. They could benefit the pharmaceutical industry in developing selective antimicrobial therapies and formulations.
We demonstrate shape recognition of microbial cells by colloidal cell imprints and selective binding with the cells of matching shape, size and surface charge.
Background and study aims
Patients with achalasia or malignancies of the head and neck are at increased risk for esophageal squamous cell carcinoma. The discussion of a screening and surveillance ...program is controversial. The aim of the present study was to determine the diagnostic potential of Lugol chromoendoscopy combined with brush cytology to diagnose esophageal squamous cell carcinoma and high-grade dysplasia. Secondly, the benefit of additional biomarkers was investigated.
Patients and methods
A total of 61 patients (21 patients with achalasia and 40 patients with malignancies of the head and neck) were included. Chromoendoscopy with 1.2% Lugol iodine solution with targeted biopsies and brush cytology processed by digital image cytometry (DICM) and fluorescence in situ hybridization (FISH) from unstained lesions (USLs) and stained mucosa were performed.
Results
Six of the 61 patients had USLs ≥2 cm. Four patients had high-grade dysplasia (HGD) or carcinoma in situ (CIS). One patient with HGD and one patient with CIS were detected only after Lugol chromoendoscopy. The sensitivity and specificity for detected HGD or CIS in USLs ≥2 cm were 100% and 96.5%. No dysplasia was found in USLs <2 cm. DNA ploidy by DNA cytometry and
p53
loss of heterozygosity (LOH) by fluorescence in situ hybridization showed no additional impact on diagnostic accuracy.
Conclusions
Lugol chromoendoscopy enhances the detection rate of high-risk lesions with dysplasia or carcinoma in situ in large unstained lesions. Biomarkers such as aneuploidy and
p53
LOH from brush cytology were not of additional benefit in this setting.
— The sound production from the Morávka fireball has been examined in detail making use of infrasound and seismic data. A detailed analysis of the production and propagation of sonic waves during the ...atmospheric entry of the Morávka meteoroid demonstrates that the acoustic energy was produced both by the hypersonic flight of the meteoroid (producing a cylindrical blast wave) and by individual fragmentation events of the meteoroid, which acted as small explosions (producing quasispherical shock waves). The deviation of the ray normals for the fragmentation events was found to be as much as 30° beyond that expected from a purely cylindrical line source blast. The main fragmentation of the bolide was confined to heights above 30 km with a possible maximum in acoustic energy production near 38 km. Seismic stations recorded both the direct arrival of the airwaves (the strongest signal) as well as air‐coupled P‐waves and Rayleigh waves (earlier signals). In addition, deep underground stations detected the seismic signature of the fireball. The seismic data alone permit reconstruction of the fireball trajectory to a precision on the order of a few degrees. The velocity of the meteoroid is much less well‐determined by these seismic data. The more distant infrasonic station detected 3 distinct signals from the fireball, identified as a thermospheric return, a stratospheric return, and an unusual mode propagating through the stratosphere horizontally and then leaking to the receiver.
Lightcurves and spectra of two of the brightest photographed bolides were studied. The Šumava bolide reached −21.5 absolute (i.e., 100 km distance) magnitude. This fragile cometary body of initial ...mass of about 5000 kg exhibited many flares and disappeared at an altitude of 59 km above the surface. The Benešov bolide (−19.5 mag) was a stony body of initial mass of about 13,000 kg which radiated down to 17 km of altitude and exhibited a bright flare at 24 km accompanied with severe fragmentation.
It is shown that the fragmentation was the main mode of ablation. By modeling the lightcurve of Šumava it is found that about 85% of the initial mass was lost in five subsequent breakups. Even between the breakups, the ablation coefficient is found to be much higher than the theoretical value for melting and vaporization.
The spectra show that the radiation of both bolides was produced by a gas heated to 4000–5000 K. At this temperature only the ablated material radiates; the radiation of the atmosphere was negligible. Atomic and molecular emissions are dominant for most of the trajectory, but near the maximum light thermal continuous radiation is also present.
The results were generalized for the entry of the comet Shoemaker–Levy 9 into the Jupiter atmosphere. Due to the high ablation, the cometary nuclei are not expected to penetrate below the jovian clouds. As the radiating volume of the associated bolides is optically thick, the bolides remain relatively faint and only weak dependence of the bolide brightness on the impactor mass is produced. The results are in accordance with the bolide and fireball observations from the Galileo spacecraft.
Aims. Lightning mapper sensors on board weather satellites can be successfully used to observe fireballs. These sensors use a very narrow spectral band at 777nm, which is only a small fraction of the ...total fireball radiation. In this spectral band, the oxygen O I-1 triplet is dominant for fast meteors and the Planck continuum can prevail in slow meteors. It is possible to estimate the meteor brightness in the visible spectral range from this narrowband radiation, but it is vital to first study the dependence of this radiation on the meteor velocity. Methods. We used observations from the well-established European Fireball Network with newly developed digital spectral cameras that allowed us to study the oxygen triplet in meteor spectra and its relation to the meteor velocity and altitude. In addition, we studied strong magnesium and sodium lines. Results. We developed a method for calibration of fireball observation reported by Geostationary Lightning Mapper (GLM) sensors on board the Geostationary Operational Environmental Satellite (GOES) weather satellites. We confirm that in slow meteors, the radiation of the Planck continuum dominates, but for faster meteors, a correction on velocity is needed. We observe that the altitude where the oxygen line was recorded can also affect the radiation at 777 nm. In addition, determining whether or not the meteor showed a bright flare could also lead to a similar effect. Thus, the meteor brightness estimate may be impacted by these characteristics. We derived simple corrections on the altitude and on the meteor brightness that helped to improve the overall precision of the magnitude estimate of our sample. This allowed us to estimate the magnitude of meteors observed by GLM with an accuracy of ~ 1 in magnitude. The Na/Mg line intensity ratio was found to be constant for velocities above 25 km/s and increasing toward lower velocities.
In patients with hepatitis C virus (HCV)-related advanced fibrosis/cirrhosis, 30% of sustained HCV clearance has been reported with pegylated interferon alpha-2a (PEG-IFN) alone, but the efficacy and ...tolerability of the PEG-IFN/ribavirin (RBV) combination remain poorly defined. A total of 124 treatment-naïve patients with biopsy proved HCV-related advanced fibrosis/cirrhosis (Ishak score F4-F6, Child-Pugh score < or =7) were randomized to 48 weeks of PEG-IFN (180 microg sc weekly) and standard dose of RBV (1000/1200 mg po daily, STD) or PEG-IFN (180 microg sc weekly) and low-dose of RBV (600/800 mg po daily, LOW). Sustained virologic response (SVR) rates with PEG-IFN/STD RBV (52%) were higher--albeit not significantly--than that with PEG-IFN/LOW RBV (38%, P = 0.153). In multivariate analysis, genotype 2/3 and a baseline platelet count > or =150 x 10(9)/L were independently associated with SVR. The likelihood of SVR was < 7% if viraemia had not declined by > or =2 log or to undetectable levels after 12 weeks. Nine adverse events in the STD RBV and 15 in the LOW RBV group were classified as severe (including two deaths); dose reductions for intolerance were required in 78% and 57% (P = 0.013), and treatment was terminated early in 23% and 27% of patients (P = n.s.). The benefit/risk ratio of treating compensated HCV-cirrhotics with STD PEG-IFN/RBV is favourable.
125 emission lines were found in a meteor spectrum obtained on August 2, 2011. The identification of most of the lines is given. The following species were found in the spectrum: CrI, FeI, MgI, SiI, ...AlI, MnI, CaI, TiI, NaI, FeII, CaII, MgII, SiII, SrII.
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