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The non-centro-symmetric semiconductor BiTeI exhibits two distinct surface terminations that support spin- split Rashba surface states. Their ambipolarity can be exploited for creating spin-polarized p-n junctions at the boundaries between domains with different surface terminations. We use scanning tunneling microscopy (STM) and spectroscopy (STS) to locate such junctions and investigate their atomic and electronic properties. The Te- and I-terminated surfaces are identified owing to their distinct chemical reactivity and an apparent height mismatch of electronic origin. The Rashba surface states are revealed in the STS spectra by the onset of a van Hove singularity at the band edge. Eventually, an electronic depletion is found on interfacial Te atoms, consistent with the formation of a space-charge area in typical p-n junctions. [ABSTRACT FROM AUTHOR]

We report a comprehensive study of the paradigmatic quasi-ID compound (TaSe4)2I performed by means of angle-resolved photoemission spectroscopy (ARPES) and first-principles electronic structure calculations. We find it to be a zero-gap semiconductor in the nondistorted structure, with non-negligible interchain coupling. Theory and experiment support a Peierls-like scenario for the charge-density wave formation below TCDW = 263 K, where the incommensurability is a direct consequence of the finite interchain coupling. The formation of small polarons, strongly suggested by the ARPES data, explains the puzzling semiconductor-to-semiconductor transition observed in transport at TCDW. [ABSTRACT FROM AUTHOR]

Boron vacancies at the Si(111):B-√3 surface are model systems in the comprehension of strongly correlated semiconductor surfaces. By using scanning tunneling spectroscopy, the origin of the single-vacancy electronic structure is addressed. It is shown to originate from the localization of a well-identified dangling-bond surface state with significant B character. The bivacancy defect, which is characterized by energy-split bonding and antibonding states, is interpreted within the textbook diatomic molecule picture. From the hopping parameter, we determine the bandwidth of the surface state from which the impurity state derives and evaluate the strength of many-body effects. Our analysis supports the realization of the Mott-Hubbard insulator state in half-filled dangling-bond surface states on √3-reconstructed surfaces, as proposed recently for SiC(0001), Sn/Ge(111), and Sn/Si(111). [ABSTRACT FROM AUTHOR]

Ab initio density-functional theory calculations, photoemission spectroscopy (PES), scanning tunneling microscopy, and spectroscopy (STM, STS) have been used to solve the 2√3 x 2√3R30 surface reconstruction observed previously by LEED on 0.5 ML K/Si:B. A large K-induced vertical lattice relaxation occurring only for 3/4 of Si adatoms is shown to quantitatively explain both the chemical shift of 1.14 eV and the ratio 1/3 measured on the two distinct B 1s core levels. A gap is observed between valence and conduction surface bands by ARPES and STS which is shown to have mainly a Si-B character. Finally, the calculated STM images agree with our experimental results. This work solves the controversy about the origin of the insulating ground state of alkali-metal/Si(111):B semiconducting interfaces which were believed previously to be related to many-body effects. [ABSTRACT FROM AUTHOR]

From scanning tunneling spectroscopy measurements, we recently found evidence for the effect of electron-phonon interactions on the lifetime of hot electrons and holes. This information was obtained by measuring the linewidth of quantum well states resulting from the confinement of Shockley states in truncated hexagonal Ag nanopyramids. In the present paper, we show that a careful analysis allows us to obtain both the intrinsic and extrinsic broadening contributions. This latter contribution results from the lossy boundary scattering which is strongly reduced in this peculiar geometry. Indeed, we deduce the energy dependence of the reflection coefficient which remains higher, as usually observed in nanostructures like adatom islands and quantum corrals. [ABSTRACT FROM AUTHOR]

In this paper, we report on the experimental determination of alkali absolute coverage in the K/Si(111):B- 2√3 x 2√3R30° surface. To this end, we carried out a comparative study with the closest system, namely, K/Si(111)-3 x 1, for which potassium coverage has been widely demonstrated to be 1/3 of a monolayer. We used x-ray photoemission spectroscopy to count and compare the number of potassium atoms in both surfaces, together with a scanning tunneling microscopy in order to check the completion of these ultrathin layers. The analysis leads to a 1/2 monolayer coverage in the 2√3 x 2√3R30° surface, that is six potassium atoms per unit cell. Assuming this coverage, we can propose a simple model structure with potassium atoms arranged in trimers; we discuss the effect of such a reconstruction in terms of two distinct "up" and "down" Si adatom sites as well as the resulting surface electronic properties. [ABSTRACT FROM AUTHOR]

Bulk Rashba systems BiTeX (X=I, Br, Cl) are emerging as important candidates for developing spintronics devices because of the coexistence of spin-split bulk and surface states, along with the ambipolar character of the surface charge carriers. The need to study the spin texture of strongly spin-orbit-coupled materials has recently promoted circular dichroic angular resolved photoelectron spectroscopy (CD-ARPES) as an indirect tool to measure the spin and the angular degrees of freedom. Here we report a detailed photon-energy-dependent study of the CD-ARPES spectra in BiTeX (X=I, Br, Cl). Our work reveals a large variation in the magnitude and sign of the dichroism. Interestingly, we find that the dichroic signal modulates differently for the three compounds and for the different spin-split states. These findings show a momentum and photon-energy dependence for the CD-ARPES signals in the bulk Rashba semiconductor BiTeX (X=I, Br, Cl). Finally, the outcome of our experiment indicates the important relation between the modulation of the dichroism and the phase differences between the wave functions involved in the photoemission process. This phase difference can be due to initial- or final-state effects. In the former case the phase difference results in possible interference effects among the photoelectrons emitted from different atomic layers and characterized by entangled spin-orbital polarized bands. In the latter case the phase difference results from the relative phases of the expansion of the final state in different outgoing partial waves. [ABSTRACT FROM AUTHOR]

We observe a giant spin-orbit splitting in the bulk and surface states of the noncentrosymmetric semiconductor BiTel. We show that the Fermi level can be placed in the valence or in the conduction band by controlling the surface termination. In both cases, it intersects spin-polarized bands, in the correspond-ing surface depletion and accumulation layers. The momentum splitting of these bands is not affected by adsorbate-induced changes in the surface potential. These findings demonstrate that two properties crucial for enabling semiconductor-based spin electronics--a large, robust spin splitting and ambipolar conduc-tion--are present in this material. [ABSTRACT FROM AUTHOR]

Objective: Sofosbuvir and ribavirin represented until recently the standard of care in hepatitis C virus genotype 2 cirrhotic patients. In registration trials, 12-16 week durations were associated with 90% sus- tained virological responses, although not confirmed by real-life studies. In Italy, various durations (12,16, 20, and 24 weeks) represent lawfully reimbursable healthcare practice. The aim is, therefore, to study the behavior of Italian clinicians and the possible impact of therapy durations on sustained virological responses and patient safety., Materials and Methods: Data of all consecutive genotype 2 cirrhotic patients who started sofosbuvir plus ribavirin therapy between January 2015 and March 2017 in 7 Italian liver clinics were collected retrospectively., Results: Overall, 147 patients (138 Child-Pugh A, mean age: 71 years) were treated. The median treatment duration was 16 weeks, but marked differences were found among the clinicians; however, the 12-week duration was not considered by the vast majority of them. Rates of intention-to-treat and per-protocol sus- tained virological responses were 95.9% and 97.1%, respectively, and neither showed differences between the various durations. No independent, sustained virological response predictors could be found, but the median baselines for Child-Pugh and Model For End-Stage Liver Disease scores were higher in non-respond- ers. Anemia was not associated with treatment duration. One case of acute kidney injury attributed to the possible sofosbuvir effect was reported., Conclusion: In genotype 2 cirrhotic patients, sofosbuvir plus ribavirin was associated with real-life-sustained virological response rates of almost 96%, without a significant impact on treatment duration provided it was longer than 12 weeks.

Background: Nonalcoholic fatty liver disease (NAFLD) is common in both prediabetic patients and healthy overweight individuals, yet it remains understudied. This study investigates the effects of hepatic steatosis on fibrosis and evaluates the major predictors of liver injury in prediabetes and whether this damage is reversible with Mediterranean diet and administration of the nutraceutical silymarin., Methods: First, a case-control study was conducted in which 212 patients with prediabetes, not known to have NAFLD, and 126 healthy controls underwent clinical evaluation, transient elastography with measurement of liver stiffness (LS) and controlled attenuation parameter (CAP). Subsequently, the 212 prediabetic patients were enrolled into a prospective randomized interventional study: 104 were allocated to Mediterranean diet alone while 108 followed Mediterranean diet plus supplementation with silymarin (a flavonolignan complex isolated from Silybum marianum and Morus alba ). The administered silymarin dose was 210 mg twice daily for 6 months. Clinical and instrumental evaluations were repeated at the end of the 6 month-study period. Prediabetics were genotyped for patatin like phospholipase domain containing 3 (PNPLA3)., Results: In the case-control study, 29% of prediabetic patients have significant fibrosis defined as LS ≥ 7.9 kPa vs only 3% of controls ( p  < 0.001). PNPLA3 genotype CG/GG are significantly associated with significant fibrosis LS ≥ 7.9 relative to CC genotype χ2(1) = 76.466, p  < 0.001. Binomial regression analysis shows that increase in BMI, ALT and AST are significantly associated with increased likelihood of significant fibrosis (χ2(7) = 191.9, p  < .001) prior to intervention. In the randomized interventional study, prediabetics following Mediterranean diet alone (group 1) experienced a significant regression of fibrosis and decrease in ALT, HbA1c, FBS after 6 months ( p  < 0.001); similar findings were observed in patients following Mediterranean diet plus silymarin regimen (group 2); group 2 had a significant decrease in HbA1c relative to group 1 (95% CI: 37.8-38.6 vs 39.5-40.3, p  < 0.001)., Conclusion: PNPLA3 genotype CG/GG and elevated BMI are the major predictors of significant fibrosis in prediabetic patients prior to intervention in this study. Mediterranean diet either alone or with silymarin treatment for 6 months leads to significant regression of liver damage and improvement of the glycemic profile in prediabetic patients. Yet, as combination treatment of silymarin with Mediterranean diet shows significant reduction of HbA1c when compared to diet alone, this suggests that silymarin may exert an independent anti-glycemic action., Competing Interests: Conflict of interestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© The Author(s) 2020.)

Background: The prevalence of nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM) is high, though its severity is often underestimated. Our aim is to provide an estimate of the prevalence of severe NAFLD in T2DM and identify its major predictors., Methods: T2DM patients ( n =328) not previously known to have NAFLD underwent clinical assessment, transient elastography with measure of liver stiffness (LS) and controlled attenuation parameter (CAP), and genotyping for patatin like phospholipase domain containing 3 ( PNPLA3 ) and 17β-hydroxysteroid-dehydrogenase type 13 ( HSD17B13 )., Results: Median LS was 6.1 kPa (4.9 to 8.6). More than one-fourth patients had advanced liver disease, defined as LS ≥7.9 kPa ( n =94/238, 29%), and had a higher body mass index (BMI) than those with a LS <7.9 kPa. Carriage of the G allele in the PNPLA3 gene was associated with higher LS, being 5.9 kPa (4.7 to 7.7) in C/C homozygotes, 6.1 kPa (5.2 to 8.7) in C/G heterozygotes, and 6.8 kPa (5.8 to 9.2) in G/G homozygotes ( P =0.01). This trend was absent in patients with ≥1 mutated HSD17B13 allele. In a multiple linear regression model, BMI and PNPLA3 genotype predicted LS, while age, gender, disease duration, and glycosylated hemoglobin did not fit into the model. None of these variables was confirmed to be predictive among carriers of at least one HSD17B13 mutated allele. There was no association between CAP and polymorphisms of PNPLA3 or HSD17B13 ., Conclusion: Advanced NAFLD is common among T2DM patients. LS is predicted by both BMI and PNPLA3 polymorphism, the effect of the latter being modulated by mutated HSD17B13 ., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2019 Korean Diabetes Association.)

Unlabelled: Hepatorenal syndrome (HRS), a serious complication of cirrhosis, is associated with high mortality without treatment. Terlipressin with albumin is effective in the reversal of HRS. Where terlipressin is not available, as in the United States, midodrine and octreotide with albumin are used as an alternative treatment of HRS. The aim was to compare the effectiveness of terlipressin plus albumin versus midodrine and octreotide plus albumin in the treatment of HRS in a randomized controlled trial. Twenty-seven patients were randomized to receive terlipressin with albumin (TERLI group) and 22 to receive midodrine and octreotide plus albumin (MID/OCT group). The TERLI group received terlipressin by intravenous infusion, initially 3 mg/24 hours, progressively increased to 12 mg/24 hours if there was no response. The MID/OCT group received midodrine orally at an initial dose of 7.5 mg thrice daily, with the dose increased to a maximum of 12.5 mg thrice daily, together with octreotide subcutaneously: initial dose 100 μg thrice daily and up to 200 μg thrice daily. Both groups received albumin intravenously 1 g/kg of body weight on day 1 and 20-40 g/day thereafter. There was a significantly higher rate of recovery of renal function in the TERLI group (19/27, 70.4%) compared to the MID/OCT group (6/21, 28.6%), P = 0.01. Improvement in renal function and lower baseline Model for End-Stage Liver Disease score were associated with better survival., Conclusion: Terlipressin plus albumin is significantly more effective than midodrine and octreotide plus albumin in improving renal function in patients with HRS., (© 2015 by the American Association for the Study of Liver Diseases.)

Background: Increasing emphasis in performance-based payment, public reporting, and quality improvement (QI) has led to widespread interest in measuring and improving the quality of care. By 2014, hospice programs will be required to report quality data to the federal government or incur financial penalties. With this increased interest in quality reporting comes an opportunity to develop informatics tools to capture data that reflect the complex practices involved in palliative care (PC). Therefore, there is a need to disseminate information on developing tools that facilitate capturing data and fostering improved performance. The Veterans Health Care Administration, a national leader in health information technology (HIT) and PC, established the Quality Improvement Resource Center (QuIRC) to develop innovative HIT tools to standardize and improve PC practices throughout the 153 Department of Veterans Affairs (VA) medical centers nationwide., Objective: The aim of the paper is to describe the development of the Palliative Care-National Clinical Template (PC-NCT) for documenting initial PC consults., Results: Domains of quality of life provided the foundation for this template. Principles of user-centered informatics design guided development activities. A national consensus panel of PC experts prioritized quality indicators as targets for QI. An interdisciplinary team of PC providers identified desired aspects of template functionality. QuIRC balanced PC providers' desired aspects of functionality against the feasibility within the VA HIT system. Formal pilot and usability testing contributed to numerous iterations of the PC-NCT currently piloted in five geographically distributed sites., Conclusion: This paper presents a robust approach to developing an informatics tool for PC practice. Data collected via the PC-NCT will bring variations in current practice into view and assist in directing resources at "important targets" for QI. Although the development of HIT tools to quantify PC practice is complex, there is enormous potential to improve the quality of care for patients and families facing serious illnesses.

Objectives: To evaluate whether, in chronic hepatitis C-positive naive patients recruited in the routine clinical setting and treated with pegylated-interferon-α2b (Peg-IFN) and ribavirin (RBV), the sustained virologic response (SVR) is durable over the long term and whether it is associated with a decrease in liver complications and incidence of glucose abnormalities., Patients and Methods: This was a prospective long-term follow-up study of 182 naive patients enrolled in 2001-2002 and treated with Peg-IFN and RBV and followed up to December 2010, with clinical, biochemical, and virological evaluations every 6-12 months., Results: None of the 115 (63.2%) sustained responders showed late viremic relapse during the follow-up. SVR was better defined at 24 weeks (16/16 relapsers, 100%) than at 12 weeks after the end of therapy (14/16 relapsers, 87.5%). On multivariable analysis, viral genotype (odds ratio 0.16, 95% confidence interval 0.07-0.36, P=0.0001) and a greater than 20% RBV reduction (odds ratio 5.21, 95% confidence interval 1.54-17.67, P=0.008) predicted long-term response (LTR) independently. The incidence of cirrhosis was significantly higher among nonresponders (21.3%) compared with long-term responders (0.9%, P≤0.0001), but the risk of developing glucose abnormalities was not significantly reduced in long-term responders (hazard ratio 1.36, P=0.363). Hepatocellular carcinoma occurred only in three cases., Conclusion: SVR achieved in patients treated in the routine clinical setting with Peg-IFN and RBV is durable over the long term and LTR significantly reduces the risk of progression to cirrhosis; however, in a population with mild liver fibrosis, the clinical impact of LTR on the risk of glucose abnormalities seems negligible.

Purpose: We developed, implemented, and evaluated a multicomponent cancer genetics toolkit designed to improve recognition and appropriate referral of individuals at risk for hereditary cancer syndromes., Methods: We evaluated toolkit implementation in the women's clinics at a large Veterans Administration medical center using mixed methods, including pre-post semistructured interviews, clinician surveys, and chart reviews, and during implementation, monthly tracking of genetic consultation requests and use of a reminder in the electronic health record. We randomly sampled 10% of progress notes 6 months before (n = 139) and 18 months during implementation (n = 677)., Results: The toolkit increased cancer family history documentation by almost 10% (26.6% pre- and 36.3% postimplementation). The reminder was a key component of the toolkit; when used, it was associated with a twofold increase in cancer family history documentation (odds ratio = 2.09; 95% confidence interval: 1.39-3.15), and the history was more complete. Patients whose clinicians completed the reminder were twice as likely to be referred for genetic consultation (4.1-9.6%, P < 0.0001)., Conclusion: A multicomponent approach to the systematic collection and use of family history by primary-care clinicians increased access to genetic services.

We report a comprehensive study of the paradigmatic quasi-1D compound (TaSe(4))(2)I performed by means of angle-resolved photoemission spectroscopy (ARPES) and first-principles electronic structure calculations. We find it to be a zero-gap semiconductor in the nondistorted structure, with non-negligible interchain coupling. Theory and experiment support a Peierls-like scenario for the charge-density wave formation below T(CDW)=263  K, where the incommensurability is a direct consequence of the finite interchain coupling. The formation of small polarons, strongly suggested by the ARPES data, explains the puzzling semiconductor-to-semiconductor transition observed in transport at T(CDW).

Background: Alcohol is a major determinant of the outcome of chronic hepatitis C virus (HCV) infection, but self-reported drinking habits lack reliability. We hypothesized that carriage of high-repetition variants (HRV) of the variable number of tandem repeats (VNTR) in exon III of the dopamine receptor D4 gene, linked to binge-drinking and risk-seeking behavior, might be a proxy measure of alcohol consumption, and aimed to verify whether it may affect histologic outcome., Methods: A cohort of HCV patients with normal or near-normal aminotransferases (N = 128) underwent a liver biopsy as part of diagnostic work-up. None admitted to exceed low-risk alcohol consumption; most (90/128, 70%) described themselves as teetotalers. They received advice on abstaining from alcohol, but not antiviral treatment. After a median follow-up period of 10 years, all underwent a second liver biopsy. HRV allele frequencies were compared with those of a group of healthy blood donors (N = 128) and related to liver histology., Results: HRV allele frequencies were 0.19 in patients and 0.16 in controls (p = 0.182). In the subgroup of patients who admittedly had consumed alcohol, 20/38 (53%) carried HRV, in comparison with 27/90 patients (30%) who had denied to consume alcohol (p = 0.026 by Fisher's exact test). Carriage of HRV was associated with higher histologic grade (p = 0.002) and stage (p = 0.009) at the final biopsy. At multivariate analysis, among a set of variables also including viral genotype, viral load, body mass index, gender, and history of alcohol consumption, only age (OR = 1.06, 95% CI 1.02 to 1.11) and HRV (OR = 3.13, 95% CI 1.28 to 7.68) were independent predictors of significant fibrosis at the end of follow-up., Conclusions: The link between HRV carriage and histologic outcome in a subgroup of HCV patients at low risk of progression underlines the need for intense scrutiny of alcohol habits in hepatitis C., (Copyright © 2013 by the Research Society on Alcoholism.)

The interleukin 28B (IL-28B) rs12979860 C/T polymorphism is a predictor of spontaneous and treatment-induced hepatitis C virus (HCV) clearance. The C/C genotype is associated with higher serum cholesterol, predictor of a favorable outcome in chronic hepatitis C. Whether IL-28B polymorphism and serum cholesterol play a role in modulating the history of mild hepatitis C is unknown. To clarify this issue, 93 untreated patients infected with HCV with normal or near-normal transaminases and an initial Ishak staging score ≤1 were investigated retrospectively in the longitudinal study (median histological follow-up of 10 years). An additional confirmatory cohort of 143 patients with chronic HCV infection and abnormal levels of transaminases was evaluated in the cross-sectional study. In the longitudinal study, at the end of follow-up, Ishak staging scores progressed more frequently among carriers of a T/* allele who had a baseline serum cholesterol ≤175 mg/dl than in remaining patients: 6/36 (change ≤0), 15/45 (change 1-2), 6/12 (change ≥3), improvement chi-square P < 0.02, OR 3.1, 95% C.I. 1.3-7.7. In the cross-sectional study, the frequency of patients carrying the T/T genotype or serum cholesterol values ≤175 mg/dl increased starting from those with a staging score ≤2 (36/76, 47.4%), to those with a staging score of 3-4 (26/41, 63.4%) and to those with a staging score of 5-6 (20/26, 76.9%, P < 0.01 for linear trend). In conclusion, the interaction between IL-28B rs12979860 T/T genotype and low serum cholesterol concentration is an independent predictor of a worse disease course among patients infected with HCV with normal or near-normal transaminases., (Copyright © 2012 Wiley Periodicals, Inc.)

Background and Aim: Carriage of the apolipoprotein E (Apo E) variants, E2, E3 and E4, affects cholesterol metabolism and may be involved in the persistence of hepatitis C virus (HCV) infection. Our aim was to verify whether carriage of specific Apo E variants modulates the course of hepatitis C., Methods: We studied a cohort of 116 HCV-positive patients (49 male subjects) with persistently normal transaminases and an Ishak staging score ≤ 2 at an initial biopsy. These untreated patients underwent regular clinical monitoring (median histological follow up: 10 years). Apo E variants were genotyped and results were related to the histological outcome., Results: The mean ± standard deviation staging scores were 0.9 ± 0.7 at entry versus 1.9 ± 1.2 at the end of follow up, P < 0.0001. Initial and final staging scores in the E3/E3 homozygotes (n = 74) were 1.0 ± 0.7 versus 2.1 ± 1.3, P < 0.0001, while in the remaining patients (n = 42) they were 0.9 ± 0.6 versus 1.5 ± 1.0, P < 0.002. A synergistic effect was observed between Apo E polymorphisms and baseline serum cholesterol values: patients not carrying any E3 allele, as well as carriers of a single E3 allele with serum cholesterol concentration > 190 mg/dL were more likely to have a favorable outcome (final vs initial staging score increased in 7/66, did not change in 10/46, and decreased in 3/4, P <0.005)., Conclusions: Some of the variability in the natural history of patients with persistently normal transaminases with initially mild hepatitis C can be related to their Apo E genetic background., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Genetic polymorphisms of interleukin-6 (IL-6) (-1363G>T, -597G>A, -572G>C, -174G>C, +2954G>C) may affect the outcomes of several diseases. This study was aimed to verify the role of these polymorphisms on the disease progression of patients with hepatitis C virus (HCV) infection and persistently normal transaminases (PNALT). A total of 121 PNALT patients did not receive any antiviral treatment but underwent periodic clinical monitoring, including repeat biopsies, for a median of 120 months. IL6-1363G>T, -597G>A, -572G>C, -174G>C, +2954G>C polymorphisms were related to histologic fibrosis progression. Among patients whose grading and staging scores increased at the end of the follow-up ≥2 Ishak points (N = 60 and N = 26, respectively), IL-6 -174G>C genotype frequencies were GG 37/66, GC 21/45, CC 2/10 (p = 0.041) and GG 18/66, GC 8/45, CC 0/10 (p = 0.040), respectively. The following frequencies were observed for the 572G>C polymorphism: GG 50/105, GC 10/16, CC 0/0, and GG 19/105, GC 7/16, CC 0/0, respectively. Grading progression was independently associated with carriage of the G allele in -174G>C polymorphism (oddd ratio = 5.07%, 95% confidence interval = 0.959-26.8, p = 0.023). Staging progression was independently associated with carriage of the C allele in -572G>C polymorphism (odd ratio = 4.60%, 95% confidence interval 1.42-14.8, p = 0.012). IL-6 polymorphisms influence histologic progression of HCV in patients with PNALT., (2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

We present a scanning tunneling microscopy investigation of the dynamics of hot electrons and holes in Ag pyramidal nanostructures. The geometry of the nanostructure leads to a strong reduction of the decay mechanism into the bulk states and then to a large reflection coefficient of the surface electronic waves. Therefore, in contrast to quantum corrals and adatom islands which show a dominant lossy scattering contribution to the linewidth, the narrow observed structures in the differential conductivity spectra reveal the expected linewidth minimum at the Fermi energy. The electron-phonon contribution to the lifetime is shown to be dominant, in agreement with previous photoemission measurements.

Background: The aim of the study was to perform a comprehensive diagnostic evaluation of six popular, non-proprietary, indirect markers of liver fibrosis in a cohort of patients with chronic hepatitis C representing the full spectrum of disease severity., Methods: A total of 167 consecutive, hepatitis C virus RNA positive, untreated patients with chronic hepatitis C were studied. Liver biopsy with histological evaluation and age/platelet index, aspartate aminotransferase/alanine aminotransferase ratio, aspartate aminotransferase to platelet ratio index, Bonacini's discriminant score, Forn's fibrosis index and FibroIndex were assessed in all patients., Results: The area under the receiver operating characteristic curves of the six tests was always greater when performed to discriminate patients with METAVIR score F4 than when assessed to discriminate patients with METAVIR score > or =F2. At step-wise discriminant analysis the only indirect marker of fibrosis entered was FibroIndex, with the following correct classification of the patients: total=52.1, patients with scores F0-F1=62.2, patients with scores F2-F3=26.0 and patients with score F4=68.4., Conclusions: The ability to correctly classify patients using a panel of non-proprietary indirect markers of liver fibrosis is far from being ideal. Among them, FibroIndex appears to possess the best discriminating capacity. The simultaneous use of several indirect markers of liver fibrosis does not improve their diagnostic accuracy.

Objectives: To evaluate whether in chronic hepatitis C-positive patients who failed to respond to interferon (IFN) monotherapy a sustained response obtained with retreatment using the combination therapy of IFN + ribavirin can be safely considered to reflect eradication of the infection., Methods: Prospective follow-up of a cohort of 97 patients who responded to retreatment with different regimens of IFN + ribavirin after failing to respond to a first IFN monotherapy course. The patients were followed throughout 7 yr of follow-up with determinations of HCV viremia every 6 months., Results: At the end of the follow-up, 11 patients (11.3%) showed a viremic reappearance. HCV late relapse rates were 0%, 13%, 20%, and 12% in patients retreated, respectively, with 3 MU IFN + ribavirin for 12 months (Group 1), 5 MU IFN + ribavirin for 12 months (Group 2), 3 MU IFN + ribavirin for 6 months (Group 3), and 5 MU IFN + ribavirin for 6 months (Group 4) (Group 2 vs Group 3, p= 0.005). The virologic relapses occurred within 2 yr from therapy withdrawal. Among patients with genotype 1 and 4, the long-term response was significantly higher in Group 2 than in Group 3 (15%vs 3%, p= 0.03). In patients with genotype 2 and 3, the long-term virological response was not affected by the different regimens., Conclusions: Nonresponders to IFN monotherapy who achieve a sustained virologic response after retreatment with IFN + ribavirin stand a discrete risk of HCV reactivation within 2 yr after therapy.

Objectives: To verify the value of indirect serum markers in the non-invasive assessment of liver fibrosis in patients with persistently normal or near normal alanine aminotransferases levels (NALT)., Design and Methods: Forty HCV RNA positive, untreated patients with NALT (30 non-drinkers) underwent two liver biopsies, with a median interval of 78.5 months. The AST/ALT ratio, age-platelet index, AST to platelet ratio index (APRI), Forns fibrosis index and Bonacini's discriminant score were simultaneously determined., Results: In 19 patients, worsening of fibrosis was observed at the second biopsy in comparison to the index biopsy. Among non-drinkers, an APRI >0.4 had a 100% sensitivity in identifying subjects with significant liver fibrosis (Ishak staging score >2) and an APRI < or =0.4 had a 100% negative predictive value in excluding significant liver fibrosis., Conclusions: APRI performs better, in comparison to all other markers, in correctly classifying patients with NALT with no progression to significant liver fibrosis.

The course of hepatitis C virus (HCV) infection carriers with normal/near-normal aminotransferases (NALT) is usually mild; however, in a few, fibrosis progression occurs. We aimed to verify whether monitoring by liver biopsy might be replaced by noninvasive methods and to identify factors associated with fibrosis progression in patients with persistently normal alanine aminotransferases. We studied 40 untreated HCV-RNA-positive subjects (22 male; median age, 44 years), who underwent two liver biopsies, with a median interval of 78.5 months, during which alanine aminotransferase concentrations (median number of determinations: 12) never exceeded 1.2 times the upper normal limit. Within 9 months from the second biopsy, they were tested by the shear elasticity probe (Fibroscan) and the artificial intelligence algorithm FibroTest. METAVIR fibrosis scores were analyzed in relationship to demographic, clinical, and viral parameters. Weighted kappa analysis was used to verify whether the results of noninvasive methods agreed with histology. Significant fibrosis (> or = F2), present at the first biopsy in only one patient (2.5%), was observed at the second biopsy in 14 patients (35%). At multivariate analysis, excess alcohol consumption in the past (>20 g/d; P = .017) and viral load (>8.0 x 10(6) copies/mL; P = .021) were independent predictors of progression. In identifying patients with significant fibrosis, inter-rater agreement was excellent for Fibroscan (weighted kappa = 1.0), and poor for FibroTest (weighted kappa = -0.041). In conclusion, among HCV carriers with NALT, Fibroscan is superior to the FibroTest in the noninvasive identification of fibrosis, for which excess alcohol consumption in the past and high viral load represent risk factors.

Purpose: Laparoscopic radical nephrectomy is being performed more commonly. To our knowledge intentional resection of the diaphragm during laparoscopic radical nephrectomy for large renal tumors has not yet been described. We detail the laparoscopic management of diaphragmatic resection., Materials and Methods: From March 1996 to February 2001, 36 patients underwent cytoreductive laparoscopic radical nephrectomy at our institution in preparation for systemic immunotherapy. Charts and operative tapes were reviewed and cases were identified in which diaphragmatic resection was performed for locally invasive tumors., Results: In 3 patients a portion of the diaphragm was dissected via laparoscopy during debulking nephrectomy. All patients had renal cell carcinoma with documented metastatic disease. The diaphragm was repaired laparoscopically using intracorporeal suturing techniques in 2 of the 3 patients and a chest tube was placed in all 3. Transient systolic hypotension and hypercarbia in 1 case resolved with manual ventilation. The chest tube was removed on postoperative days 2 to 4. There were no complications and no ipsilateral pleural metastasis was identified at an average of 6 weeks (range 2 to 23) of followup., Conclusions: A portion of the diaphragm may be intentionally resected during laparoscopic radical nephrectomy. This maneuver may be successfully managed without conversion to an open procedure. In cases of a large diaphragmatic defect or the potential for coagulopathy postoperatively a chest tube should be inserted. Potential invasion of the diaphragm by large tumors should not be considered a contraindication to cytoreductive laparoscopic radical nephrectomy.

To determine whether a higher dosage of interferon (IFN) associated with ribavirin and/or prolonged time of administration may improve therapeutic efficacy, we conducted a 4-arm randomized trial on patients with chronic hepatitis C not responding to one or more previous treatment courses with IFN monotherapy. Group 1 (n = 139) received 3 million units (MU) IFN-alpha2b 3 times a week (t.i.w.) plus ribavirin 1,000 mg/d for 12 months; group 2 (n = 162) received 5 MU t.i.w. plus ribavirin for 12 months; group 3 (n = 142) received 3 MU t.i.w. plus ribavirin for 6 months; and group 4 (n = 151) received 5 MU t.i.w. plus ribavirin for 6 months. The primary end point was hepatitis C virus (HCV)-RNA clearance at the end of 6-month follow-up. HCV-RNA was negative in 15% of group 1, 23% of group 2, 11% of group 3, 16% of group 4 (group 2 vs. group 3, P =.04). Among patients with genotypes 1 and 4, sustained response was significantly higher in group 2 vs. group 3 (18% vs. 7%, P =.03; group 1 = 9%, group 4 = 12%, P = not significant [NS]). In patients with genotypes 2 and 3, sustained virologic response was not affected by the different regimens (group 1 = 32%, group 2 = 30%, group 3 = 30%, group 4 = 35%, P = NS). In conclusion, about 23% of nonresponders to IFN monotherapy may achieve a sustained response if re-treated by 5 MU t.i.w. IFN plus ribavirin 1,000 mg/d for 1 year. Patients with genotype 1 should receive a high dosage of IFN plus ribavirin for 12 months, whereas therapy for patients with genotype 2 or 3 should be less aggressive.

To analyze interleukin-2-dependent immunoregulatory function in hepatitis B virus infection and in other forms of viral hepatitis, levels of soluble interleukin-2 receptors (sIL-2R) were measured by an enzyme-linked assay in sera from patients with acute and chronic viral hepatitis of different etiology. Increased sIL-2R levels were detected in the early phase of acute hepatitis type A and type B, but not during acute non-A, non-B hepatitis. Among 46 patients with chronic hepatitis B virus infection, levels of sIL-2R were significantly increased only in cases with chronic active hepatitis, while they were about normal in chronic persistent hepatitis or in healthy carriers of the infection. These differences were independent of virus replication, being maintained when patients were stratified according to HBeAg/anti-HBe status and to serum HBV-DNA. Nine patients with chronic active hepatitis type B and high sIL-2R levels at presentation were followed prospectively for two to eight years, and in HBeAg-positive patients, the behavior of receptor levels closely paralleled disease activity. These results, which may reflect increased shedding of IL-2R by activated T lymphocytes in patients with active destruction of HBV infected hepatocytes, indicate the usefulness and potential prognostic importance of serum sIL-2R determination in patients with chronic viral hepatitis. Patients with chronic non-A, non-B hepatitis had much lower sIL-2R levels, although their liver disease was similar to hepatitis B cases, suggesting that different pathogenetic mechanisms operate in these patients.