Detection of KRAS mutations in archival pathology samples is critical for therapeutic appropriateness of anti-EGFR monoclonal antibodies in colorectal cancer. We compared the sensitivity, ...specificity, and accuracy of Sanger sequencing, ARMS-Scorpion (TheraScreen®) real-time polymerase chain reaction (PCR), pyrosequencing, chip array hybridization, and 454 next-generation sequencing to assess KRAS codon 12 and 13 mutations in 60 nonconsecutive selected cases of colorectal cancer. Twenty of the 60 cases were detected as wild-type KRAS by all methods with 100% specificity. Among the 40 mutated cases, 13 were discrepant with at least one method. The sensitivity was 85%, 90%, 93%, and 92%, and the accuracy was 90%, 93%, 95%, and 95% for Sanger sequencing, TheraScreen real-time PCR, pyrosequencing, and chip array hybridization, respectively. The main limitation of Sanger sequencing was its low analytical sensitivity, whereas TheraScreen real-time PCR, pyrosequencing, and chip array hybridization showed higher sensitivity but suffered from the limitations of predesigned assays. Concordance between the methods was k = 0.79 for Sanger sequencing and k > 0.85 for the other techniques. Tumor cell enrichment correlated significantly with the abundance of KRAS-mutated deoxyribonucleic acid (DNA), evaluated as ΔCt for TheraScreen real-time PCR (P = 0.03), percentage of mutation for pyrosequencing (P = 0.001), ratio for chip array hybridization (P = 0.003), and percentage of mutation for 454 next-generation sequencing (P = 0.004). Also, 454 next-generation sequencing showed the best cross correlation for quantification of mutation abundance compared with all the other methods (P < 0.001). Our comparison showed the superiority of next-generation sequencing over the other techniques in terms of sensitivity and specificity. Next-generation sequencing will replace Sanger sequencing as the reference technique for diagnostic detection of KRAS mutation in archival tumor tissues.
We obtain 40-Gb/s all-optical clock recovery by means of a very simple scheme. We use a high finesse low-loss Fabry-Perot filter and a semiconductor optical amplifier acting as an amplitude ...equalizer. The recovered clock signal shows large locking range, low amplitude fluctuation, and limited time jitter.
Conventional criteria for liver transplantation for patients with hepatocellular carcinoma are single HCC ≤ 5 cm or less than or equal to three HCCs ≤ 3 cm. We prospectively evaluated the possibility ...of slightly extending these criteria in a down‐staging protocol, which included patients initially outside conventional criteria: single HCC 5–6 cm or two HCCs ≤ 5 cm or less than six HCCs ≤ 4 cm and sum diameter ≤ 12 cm, but within Milan criteria in the active tumors after the down‐staging procedures. The outcome of patients down‐staged was compared to that of Milan criteria after liver transplantation and since the first evaluation according to an intention‐to‐treat principle. From 2003 to 2006, 177 patients with HCC were considered for transplantation: the transplantation rate was comparable between the Milan and down‐staging groups: 88/129 cases (68%) versus 32/48 cases (67%), respectively. At a median follow‐up of 2.5 years after transplantation, the 1 and 3 years' disease‐free survival rates were comparable: 80% and 71% in the Milan group versus 78% and 71% in the down‐staging. The actuarial intention‐to‐treat survival was 27/48 patients (56.3%) in the down‐staging and 81/129 cases (62.8%) in the Milan group, p = n.s. The proposed down‐staging criteria provide a comparable outcome to the conventional criteria.
This study of a new down‐staging protocol for patients with HCC moderately beyond the Milan criteria on waiting list for liver transplantation shows that both the intention‐to‐treat analysis and the post‐operative outcome were comparable between down‐staging and conventional criteria group. See also editorial by Lo in this issue on page 2485.
Antimony-telluride based phase-change materials doped with Sn have been proposed to be ideal materials for improving the performance of phase-change memories. It is well known that Sb70Te30 thin ...films show a sharp fall in the electrical resistance in a narrow temperature range when heating. Therefore, it is interesting to study the effect of adding Sn into this composition. In this work, undoped and Sn-doped Sb–Te thin films of composition SnxSb0.70Te0.30100-x, with x = 0.0, 2.5, 5.0 and 7.5 at. %, have been obtained by pulsed laser deposition. Their electrical resistance has been measured while heating from room temperature to 650 K. A sharp fall in the electrical resistance, associated to the glass-crystal transition, has been detected in all the samples within a narrow temperature range. The onset temperature of this transformation increases with the Sn content. Both as-obtained and thermally-treated films have been structurally characterized by X-ray and by Raman spectroscopy. We have compared the results among these compositions in terms of the identified crystallization products, transformation onset temperatures, transformation temperature ranges and amorphous/crystallized electrical resistance ratio. We have found that the frequency of the Raman modes decreases with Sn-doping. Finally, in order to study the electronic structure and to determine the band gap, the frequencies of the allowed Raman modes and the vibration directions of the Sb70Te30 compound, Density Functional Theory based ab initio calculations have been performed as a function of the Sn concentration.
•Thermally-treated films show the same crystalline structure as their parent powders.•A sharp fall in the electrical resistance is associated to the glass-crystal transition.•Key parameters show good values for the application in non-volatile memories.•Sn dopant induces an acceptor impurity level in Sb70Te30 electronic band-structure.•The doped system has a direct band gap, nearly independent of the Sn concentration.
In this work we present an experimental and theoretical study from first-principles of the structural, electronic, and hyperfine properties of Ta-doped In2O3 semiconductor. The ab initio electronic ...structure calculations in the Ta-diluted In2O3 system enabled to obtain the structural lattice distortions and the hyperfine parameters when the Ta atom is placed at each cationic site of the bixbyite crystal structure. To this purpose we used the full-potential augmented plane wave plus local orbital (FP-APW+lo) method, within the density functional theory. The obtained results indicate that the substitutional Ta probe-impurity produces strong changes on the local structure. In addition, we performed accurate time-differential perturbed γ–γ angular correlations (TDPAC) key experiments in 181Hf(→181Ta)-implanted In2O3 samples with high crystallinity, in order to obtain high quality measurements of the electric-field gradient tensor (EFG) that unraveled the controversy settled in the literature and overcome dissimilar interpretations of previously reported TDPAC experiments. The experiments were performed at room temperature in air, after each step of a series of thermal annealing treatments in air at increasing temperatures in order to remove radiation damage and locate the 181Hf probes at substitutional cationic sites. We succeeded to obtained two well-defined hyperfine interactions that were assigned to 181Ta probes located at the two defect-free inequivalent cationic sites of the In2O3 crystal structure. The EFG calculations are in excellent agreement with the results of these TDPAC measurements, and show that the largest component of the diagonalized EFG, V 33, at the Ta site has mainly p character. The accuracy of the experiments together with the reliable and precise ab initio results allowed a definitive determination of the EFG at both cationic sites in this system. Formation energy calculations of defects were needed to determine the charge state of the 181Ta impurity, which agrees with a semiconducting character for the In2O3:Ta doped system.
Pretransplant donor biopsy (PTDB)‐based marginal donor allocation systems to single or dual renal transplantation could increase the use of organs with Kidney Donor Profile Index (KDPI) in the ...highest range (e.g. >80 or >90), whose discard rate approximates 50% in the United States. To test this hypothesis, we retrospectively calculated the KDPI and analyzed the outcomes of 442 marginal kidney transplants (340 single transplants: 278 with a PTDB Remuzzi score <4 median KDPI: 87; interquartile range (IQR): 78–94 and 62 with a score = 4 median KDPI: 87; IQR: 76–93; 102 dual transplants median KDPI: 93; IQR: 86–96) and 248 single standard transplant controls (median KDPI: 36; IQR: 18–51). PTDB‐based allocation of marginal grafts led to a limited discard rate of 15% for kidneys with KDPI of 80–90 and of 37% for kidneys with a KDPI of 91–100. Although 1‐year estimated GFRs were significantly lower in recipients of marginal kidneys (−9.3, −17.9 and −18.8 mL/min, for dual transplants, single kidneys with PTDB score <4 and =4, respectively; p < 0.001), graft survival (median follow‐up 3.3 years) was similar between marginal and standard kidney transplants (hazard ratio: 1.20 95% confidence interval: 0.80–1.79; p = 0.38). In conclusion, PTDB‐based allocation allows the safe transplantation of kidneys with KDPI in the highest range that may otherwise be discarded.
This study shows that the standardized assessment of formalin‐fixed pretransplant biopsies helps recover donors with KDPI in the highest range that would be otherwise discarded, and by providing the expected graft outcomes based on KDPI and pretransplant biopsy, it guides the clinician facing the difficult decision whether to accept or reject these organs. See editorial by Gupta et al on page 2444.
(Sb0.70Te0.30)100-xSnx alloys (with x = 0, 2.5, 5.0 and 7.5 at. %) have been synthesized and characterized in order to determine the crystalline structure and properties of materials obtained upon ...solidification and to extract information about the location of the Sn atom in the Sb-Te matrix. Powder X-ray diffraction (XRD) has been used to determine the crystalline structure, whereas Mössbauer spectroscopy has been utilized to determine the localization and the local structure of the Sn atom in the Sb-Te matrix through the hyperfine interactions of the 119Sn probe with its environment. We found that Sb70Te30 crystallizes in a trigonal structure belonging to P-3m1 space group, while the doping with Sn leads to structural distortions of the unit cell that can be described, for all the Sn concentrations, with the C2/m space group. The hyperfine parameters indicate that tin behaves as Sn(II) and has a slightly distorted environment. Finally, in order to extract all the information that the experimental results contain and to determine the preferential site occupied by the Sn impurities in the Sb-Te matrix, we have performed ab-initio calculations within the framework of the Density Functional Theory. The theoretical results enable us to determine the structural and electronic ground state of (Sb0.70Te0.30)100-xSnx compounds and to confirm that Sn atoms substitute Sb atoms in the Sb-Te host.
•Sn atoms in Sn–doped Sb70Te30 structure replace one of Sb sites.•That leads to distortion of the crystal lattice resulting in a change of space group.•From P-3m1 for un-doped to C2/m for Sn-doped samples.•For higher Sn concentration, higher is the degree of the lattice distortion.
Abstract Background Few papers deal with pathologic characteristics and outcome of the 3 different cholangiocarcinomas based on location (intrahepatic, peri-hilar, distal). There is little evidence ...regarding similarity and differences. Patients and Methods From two tertiary referral Italian Centers (in Bologna and Verona), 479 patients with cholangiocarcinoma were evaluated between 1980 and 2011. Several pathologic characteristics and their impact on survival were analyzed among resected patients for cholangiocarcinomas depending on the site of origin. Results Tumour location was intrahepatic in 172 cases (36%), peri-hilar in 243 (51) and distal in 64(13%). Curative resection was performed in 339 (70%) patients. Intrahepatic cholangiocarcinoma showed higher probability to achieve R0 resection (81%), but was more frequently associated with presence of microvascular invasion (71%). Distal cholangiocarcinoma presented less R0 resections (58%), higher lymphnode involvement (60%) and lower microvascular invasion (49%). Hilar cholangiocarcinoma had intermediate characteristics (R0: 65% of cases). Median follow up was 30.2 ± 38 months; the 5 years overall survival was 31% in the resected population. Overall survival curves were similar among the three groups. At univariate analysis surgical margins, lymphnode status, perineural invasion, T category, TNM stage, microvascular invasion, tumour grading had significant impact on survival. At multivariate analysis, only microvascular invasion was significantly related to long term results (HR = 1,7; 95% CI = 1,0–2,5)”. Conclusion Micro-vascular invasion has the strongest impact on survival in all three types of cholangiocarcinoma. In case of comparable pathologic characteristics and stage, the three tumors show similar outcome; depending on location, it shows a different tendency to invade bordering structures which affect the outcome.
Cardiac allograft vasculopathy (CAV) is an obliterative and diffuse type of coronaropathy that develops in the transplanted human heart, representing a major cause of graft failure and mortality. ...Nowadays the gold standard for the diagnosis of CAV is coronary angiography (CA). Non-invasive CAV detection, especially in the early stages of the disease, is still challenging. Our study aimed to investigate the role of speckle tracking echocardiography (STE), in particular three-layer STE, in predicting CAV at early stages, and if other traditional echocardiographic, clinical or biochemical parameters could relate to CAV. The study population was composed of a total of 33 heart transplanted patients, divided accordingly to the presence or absence of CAV (12 CAV+ , 22 CAV−). All subjects underwent a complete transthoracic echocardiographic examination on the same day of the CA, and all conventional parameters of myocardial function were obtained, including strain values assessed by STE. Strain values were significantly reduced in presence of CAV, at each myocardial layer but in particular the endocardial-epicardial gradient (− 4.15 ± 1.6 vs − 1.7 ± 0.4% < .0001) that was also highly predictive of CAV (AUC at ROC curve 0.97). Among diastolic parameters, the E wave deceleration time (DT) and the mean E/e′ ratio were strongly positively associated with CAV. In our population, left ventricular global longitudinal strain (GLS), layer-specific GLS and the endocardial-epicardial LS gradient, E wave DT and E/e′ ratio were the best independent non-invasive predictors of CAV.
Interstitial Lung Disease in the Elderly Patterson, Karen C., MD; Shah, Rupal J., MD; Porteous, Mary K., MD ...
Chest,
04/2017, Letnik:
151, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Background Despite the relationship between idiopathic pulmonary fibrosis (IPF) and advancing age, little is known about the epidemiology of interstitial lung disease (ILD) in the elderly. We ...describe the diagnoses, clinical characteristics, and outcomes of patients who were elderly at the time of ILD diagnosis. Methods Among subjects from a prospective cohort study of ILD, elderly was defined as age ≥ 70 years. Diagnoses were derived from a multidisciplinary review. Differences between elderly and nonelderly groups were determined using the χ2 test and analysis of variance. Results Of the 327 subjects enrolled, 80 (24%) were elderly. The majority of elderly subjects were white men. The most common diagnoses were unclassifiable ILD (45%), IPF (34%), connective tissue disease (CTD)-ILD (11%), and hypersensitivity pneumonitis (8%). Most elderly subjects (74%) with unclassifiable ILD had an imaging pattern inconsistent with usual interstitial pneumonia (UIP). There were no significant differences in pulmonary function or 3-year mortality between nonelderly and elderly subjects combined or in a subgroup analysis of those with IPF. Conclusions Although IPF was the single most common diagnosis, the majority of elderly subjects had non-IPF ILD. Our findings highlight the need for every patient with new-onset ILD, regardless of age, to be surveyed for exposures and findings of CTD. Unclassifiable ILD was common among the elderly, but for most, the radiographic pattern was inconsistent with UIP. Although the effect of ILD may be more pronounced in the elderly due to reduced global functionality, ILD was not more severe or aggressive in this group.
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