Accuracy of Transient Elastography in Assessing Fibrosis at Diagnosis in Naïve Patients With Primary Biliary Cholangitis: A Dual Cut-Off Approach.

BACKGROUND AND AIMS: Liver fibrosis holds a relevant prognostic meaning in primary biliary cholangitis (PBC). Noninvasive fibrosis evaluation using vibration-controlled transient elastography (VCTE) is routinely performed. However, there is limited evidence on its accuracy at diagnosis in PBC. We aimed to estimate the diagnostic accuracy of VCTE in assessing advanced fibrosis (AF) at disease presentation in PBC. APPROACH AND RESULTS: We collected data from 167 consecutive treatment-naïve PBC patients who underwent liver biopsy (LB) at diagnosis at six Italian centers. VCTE examinations were completed within 12 weeks of LB. Biopsies were scored by two blinded expert pathologists, according to the Ludwig system. Diagnostic accuracy was estimated using the area under the receiver operating characteristic curves (AUROCs) for AF (Ludwig stage ≥III). Effects of biochemical and clinical parameters on liver stiffness measurement (LSM) were appraised. The derivation cohort consisted of 126 patients with valid LSM and LB; VCTE identified patients with AF with an AUROC of 0.89. LSM cutoffs ≤6.5 and >11.0 kPa enabled to exclude and confirm, respectively, AF (negative predictive value [NPV] = 0.94; positive predictive value [PPV] = 0.89; error rate = 5.6%). These values were externally validated in an independent cohort of 91 PBC patients (NPV = 0.93; PPV = 0.89; error rate = 8.6%). Multivariable analysis found that the only parameter affecting LSM was fibrosis stage. No association was found with BMI and liver biochemistry. CONCLUSIONS: In a multicenter study of treatment-naïve PBC patients, we identified two cutoffs (LSM ≤6.5 and >11.0 kPa) able to discriminate at diagnosis the absence or presence, respectively, of AF in PBC patients, with external validation. In patients with LSM between these two cutoffs, VCTE is not reliable and liver biopsy should be evaluated for accurate disease staging. BMI and liver biochemistry did not affect LSMs.

Trace-element XAFS sensitivity: a stress test for a new XRF multi-detector.

X-ray absorption fine-structure (XAFS) spectroscopy can assess the chemical speciation of the elements providing their coordination and oxidation state, information generally hidden to other techniques. In the case of trace elements, achieving a good quality XAFS signal poses several challenges, as it requires high photon flux, counting statistics and detector linearity. Here, a new multi-element X-ray fluorescence detector is presented, specifically designed to probe the chemical speciation of trace 3d elements down to the p.p.m. range. The potentialities of the detector are presented through a case study: the speciation of ultra-diluted elements (Fe, Mn and Cr) in geological rocks from a calcareous formation related to the dispersal processes from Ontong (Java) volcanism (mid-Cretaceous). Trace-elements speciation is crucial in evaluating the impact of geogenic and anthropogenic harmful metals on the environment, and to evaluate the risks to human health and ecosystems. These results show that the new detector is suitable for collecting spectra of 3d elements in trace amounts in a calcareous matrix. The data quality is high enough that quantitative data analysis could be performed to determine their chemical speciation.

Optimization of a Low-Power Chemoresistive Gas Sensor: Predictive Thermal Modelling and Mechanical Failure Analysis.

The substrate plays a key role in chemoresistive gas sensors. It acts as mechanical support for the sensing material, hosts the heating element and, also, aids the sensing material in signal transduction. In recent years, a significant improvement in the substrate production process has been achieved, thanks to the advances in micro- and nanofabrication for micro-electro-mechanical system (MEMS) technologies. In addition, the use of innovative materials and smaller low-power consumption silicon microheaters led to the development of high-performance gas sensors. Various heater layouts were investigated to optimize the temperature distribution on the membrane, and a suspended membrane configuration was exploited to avoid heat loss by conduction through the silicon bulk. However, there is a lack of comprehensive studies focused on predictive models for the optimization of the thermal and mechanical properties of a microheater. In this work, three microheater layouts in three membrane sizes were developed using the microfabrication process. The performance of these devices was evaluated to predict their thermal and mechanical behaviors by using both experimental and theoretical approaches. Finally, a statistical method was employed to cross-correlate the thermal predictive model and the mechanical failure analysis, aiming at microheater design optimization for gas-sensing applications.

Multiclass HCV resistance to direct-acting antiviral failure in real-life patients advocates for tailored second-line therapies.

BACKGROUND & AIMS: Despite the excellent efficacy of direct-acting antivirals (DAA) reported in clinical trials, virological failures can occur, often associated with the development of resistance-associated substitutions (RASs). This study aimed to characterize the presence of clinically relevant RASs to all classes in real-life DAA failures. METHODS: Of the 200 virological failures that were analyzed in 197 DAA-treated patients, 89 with pegylated-interferon+ribavirin (PegIFN+RBV) and 111 without (HCV-1a/1b/1g/2/3/4=58/83/1/6/24/25; 56.8% treatment experienced; 65.5% cirrhotic) were observed. Sanger sequencing of NS3/NS5A/NS5B was performed by home-made protocols, at failure (N=200) and whenever possible at baseline (N=70). RESULTS: The majority of the virological failures were relapsers (57.0%), 22.5% breakthroughs, 20.5% non-responders. RAS prevalence varied according to IFN/RBV use, DAA class, failure type and HCV genotype/subtype. It was 73.0% in IFN group vs 49.5% in IFN free, with the highest prevalence of NS5A-RASs (96.1%), compared to NS3-RASs (75.9% with IFN, 70.5% without) and NS5B-RASs (66.6% with IFN, 20.4% without, in sofosbuvir failures). In the IFN-free group, RASs were higher in breakthrough/non-responders than in relapsers (90.5% vs 40.0%, P<.001). Interestingly, 57.1% of DAA IFN-free non-responders had a misclassified genotype, and 3/4 sofosbuvir breakthroughs showed the major-RAS-S282T, while RAS-L159F was frequently found in sofosbuvir relapsers (18.2%). Notably, 9.0% of patients showed also extra target RASs, and 47.4% of patients treated with ≥2 DAA classes showed multiclass resistance, including 11/11 NS3+NS5A failures. Furthermore, 20.0% of patients had baseline-RASs, which were always confirmed at failure. CONCLUSIONS: In our failure setting, RAS prevalence was remarkably high in all genes, with a partial exception for NS5B, whose limited resistance is still higher than previously reported. This multiclass resistance advocates for HCV resistance testing at failure, in all three genes for the best second-line therapeutic tailoring.

Treatment of hepatitis C virus infection with direct-acting antiviral drugs is safe and effective in patients with hemoglobinopathies.

Progression of liver fibrosis in patients with hemoglobinopathies is strongly related to the severity of iron overload and the presence of chronic hepatitis C virus (HCV) infection. Effective iron chelation therapy and HCV infection eradication may prevent liver complications. The European Association for the Study of the Liver guidelines recommend interferon-free regimens for the treatment of HCV infection in patients with hemoglobinopathies. However, data regarding the use of direct-acting antiviral drugs (DAAs) in this patient population are few. This observational study evaluated the safety and efficacy of therapy with DAAs in an Italian cohort of patients with hemoglobinopathies, chronic HCV infection and advanced liver fibrosis. Between March 2015 and December 2016, 139 patients received DAAs and completed 12 weeks of follow up after the end of treatment for the evaluation of sustained virological response (12SVR). The 12SVR (93.5%) was comparable with that typically observed in cirrhotic patients without hemoglobinopathies. Three patients died during the period of observation of causes unrelated to DAAs. One patient did not achieve a virological response and five (3.6%) relapsed during 12 weeks of follow-up after the end of therapy. In addition, patients showed significant reductions in serum ferritin at 12 weeks to levels similar to those observed in a control group of 39 patients with thalassemia major without HCV infection, who adhered to chelation therapy and had no overt iron overload. In conclusion, the use of DAAs appears to be safe and effective in patients with hemoglobinopathies and advanced liver disease due to HCV.

Inherent transcriptional signatures of NK cells are associated with response to IFNα + rivabirin therapy in patients with Hepatitis C Virus.

BACKGROUND: Differences in the expression of Natural Killer cell receptors have been reported to reflect divergent clinical courses in patients with chronic infections or tumors. However, extensive molecular characterization at the transcriptional level to support this view is lacking. The aim of this work was to characterize baseline differences in purified NK cell transcriptional activity stratified by response to treatment with PEG-IFNα/RBV in patients chronically infected with HCV. METHODS: To this end we here studied by flow cytometer and gene expression profile, phenotypic and transcriptional characteristics of purified NK cells in patients chronically infected with HCV genotype-1 virus who were subsequently treated with PEG-IFNα/RBV. Results were further correlated with divergent clinical response obtained after treatment. RESULTS: The pre-treatment transcriptional patterns of purified NK cells from patients subsequently undergoing a sustained virologic response (SVR) clearly segregated from those of non-responder (NR) patients. A set of 476 transcripts, including molecules involved in RNA processing, ubiquitination pathways as well as HLA class II signalling were differently expressed among divergent patients. In addition, treatment outcome was associated with differences in surface expression of NKp30 and NKG2D. A complex relationship was observed that suggested for extensive post-transcriptional editing. Only a small number of the NK cell transcripts identified were correlated with chronic HCV infection/replication indicating that inherent transcriptional activity prevails over environment effects such as viral infection. CONCLUSIONS: Collectively, inherent/genetic modulation of NK cell transcription is involved in setting the path to divergent treatment outcomes and could become useful to therapeutic advantage.

Therapeutic management of chronic hepatitis B in clinical practice: a region-wide survey.

GOALS: To characterize the clinical and treatment pattern in a large population of hepatitis B virus (HBV) patients managed at tertiary referral centers in clinical practice. BACKGROUND: Successful treatment, either with interferon (IFN) or nucleos(t)ide analogs (NUCs), of chronic HBV infection is associated with improved long-term patient outcome. However, in clinical practice, the actual management of these patients is not well characterized, and data regarding treatment pattern in this setting are lacking. METHODS: In this cross-sectional study, we evaluated 505 patients chronically infected with HBV alone and who had at least 1-year follow-up. We assessed indication to, rate of, and type of treatment as well as the characteristics of treated patients. RESULTS: Overall prevalence of positivity for HBe antigen was 19.3%, and the majority of patients had chronic hepatitis (47.5%). Non-Italian patients represented approximately one third of the population (27.1%). Among patients with indication to antiviral therapy (n=318), treatment was actually carried out in 264 patients (83.0%), prevalently with NUCs (65.9%). IFN-treated patients were younger (P<0.001), more frequently male (P=0.025) and HBeAg positive (P=0.003), and less frequently cirrhotics (P<0.001) as compared with patients treated with NUCs. CONCLUSIONS: In a geographical area with a low positivity for HBe antigen, antiviral therapy is actually carried out in the majority of patients who have indication to treatment, prevalently with NUCs, whereas IFN treatment is more frequently carried out in young, HBe antigen-positive patients who do not have advanced liver disease.

Pityriasis rosea in a hepatitis B-positive patient treated with pegylated interferon α2a: report of a case and review of the literature.

Pityriasis rosea (PR) is an acute, self-limiting exanthematous disease caused by the endogenous reactivation of human herpesvirus (HHV)-6 and/or HHV-7 infection in conditions of altered immunity. In addition, many drugs have been incriminated as possible triggers of PR-like eruptions, characterized by clinical, morphological and histopathological features that differ from typical PR. Here, we report a case of PR in a patient with chronic hepatitis B, receiving pegylated interferon α2a (PEG-IFN-α2a). PR, arising after the second administration of the PEG-IFN-α2a, might be considered a clinical expression of the patient's altered immune condition as reported in the immune reconstitution inflammatory syndrome affecting patients with human immunodeficiency virus infection after high-dose antiretroviral therapy.

Activating NK cell receptor expression/function (NKp30, NKp46, DNAM-1) during chronic viraemic HCV infection is associated with the outcome of combined treatment.

Specific NK cell killer inhibitory receptor (KIR):HLA haplotype combinations have been associated with successful clearance of acute and chronic HCV infection. Whether an imbalance of activating NK cell receptors also contributes to the outcome of treatment of chronic HCV infection, however, is not known. We studied peripheral NK cell phenotype and function in 28 chronically viraemic HCV genotype I treatment-naïve patients who underwent treatment with pegylated IFN-α and ribavirin. At baseline, chronically infected patients with sustained virological response (SVR) had reduced CD56(bright) CD16(+/-) cell populations, increased CD56(dull) CD16(+) NK cell proportions, and lower expression of NKp30, DNAM-1, and CD85j. Similarly, reduced NK cell IFN-γ production but increased degranulation was observed among nonresponding (NR) patients. After treatment, CD56(bright) CD16(+/-) NK cell numbers increased in both SVR and NR patients, with a parallel significant increase in activating NKp30 molecule densities in SVR patients only. In vitro experiments using purified NK cells in the presence of rIL-2 and IFN-α confirmed upregulation of NKp30 and also of NKp46 and DNAM-1 in patients with subsequent SVR. Thus, differences in patient NK cell receptor expression and modulation during chronic HCV-1 infection are associated with subsequent outcome of standard treatment. Individual activating receptor expression/function integrates with KIR:HLA genotype carriage to determine the clearance of HCV infection upon treatment.

Peripheral blood cytopaenia limiting initiation of treatment in chronic hepatitis C patients otherwise eligible for antiviral therapy.

BACKGROUND: In patients with chronic hepatitis C virus (HCV) infection, the presence of peripheral blood cytopaenia may represent an obstacle to pegylated interferon and ribavirin treatment. AIMS: To evaluate the prevalence of anaemia, neutropaenia and thrombocytopaenia potentially limiting initiation of pegylated interferon and ribavirin treatment in patients with chronic HCV infection who were otherwise eligible for antiviral therapy. METHODS: We studied 3059 consecutive anti-HCV and HCV-RNA positive patients referred to our centre to be evaluated for antiviral therapy from June 2002 to May 2011. The European Association for the Study of Liver HCV guidelines were applied to assess eligibility for antiviral therapy. RESULTS: In the study cohort, 1,521 patients (49.7%) were not eligible for treatment because of reasons different from haematological abnormalities. In the remaining 1,538 patients the overall prevalence of any peripheral blood cytopaenia potentially preventing patients from being treated with antiviral therapy was 15.1%. In particular, anaemia (haemoglobin level < 12 g/dL for women, <13 g/dL for men) was a relative contraindication to treatment in 8.9% (137/1,538) of the patients, while thrombocytopaenia (platelet count cut-off, 90 × 10(9) /L) and neutropaenia (absolute neutrophil count < 1.5 × 10(9) /L) limited treatment in 6.5% (100/1358) and 3.2% (48/1358) of patients respectively. These haematological abnormalities were more prevalent in patients with older age (P < 0.004) and cirrhosis (P < 0.001). CONCLUSIONS: The presence of peripheral blood cytopaenia may potentially limit initiation of antiviral therapy in one in every seven patients with chronic HCV infection who are otherwise eligible for treatment.

MEMS Membranes with Nanoscale Holes for Analytical Applications.

Micro-electro-mechanical membranes having nanoscale holes were developed, to be used as a nanofluidic sample inlet in novel analytical applications. Nanoscopic holes can be used as sampling points to enable a molecular flow regime, enhancing the performance and simplifying the layout of mass spectrometers and other analytical systems. To do this, the holes must be placed on membranes capable of consistently withstanding a pressure gradient of 1 bar. To achieve this goal, a membrane-in-membrane structure was adopted, where a larger and thicker membrane is microfabricated, and smaller sub-membranes are then realized in it. The nanoscopic holes are opened in the sub-membranes. Prototype devices were fabricated, having hole diameters from 300 to 600 nm, a membrane side of 80 µm, and a simulated maximum displacement of less than 150 nm under a 1 bar pressure gradient. The obtained prototypes were tested in a dedicated vacuum system, and a method to calculate the effective orifice diameter using gas flow measurements at different pressure gradients was implemented. The calculated diameters were in good agreement with the target diameter sizes. Micro-electro-mechanical technology was successfully used to develop a novel micromembrane with nanoscopic holes, and the fabricated prototypes were successfully used as a gas inlet in a vacuum system for mass spectrometry and other analytical systems.

Hepatic Elastometry and Glissonian Line in the Assessment of Liver Fibrosis.

The aim of this study was to identify a method for staging hepatic fibrosis using a non-invasive, rapid and inexpensive technique based on ultrasound morphologic hepatic features. A total of 215 patients with different liver diseases underwent B-mode (2-D brightness mode) ultrasonography, vibration-controlled transient elastography, 2-D shear wave elastography and measurement of the controlled attenuation parameter with transient elastography. B-Mode images of the anterior margin of the left lobe were obtained and processed with automatic Genoa Line Quantification (GLQ) software based on a neural network for staging liver fibrosis. The accuracy of GLQ was 90.6% during model training and 78.9% in 38 different patients with concordant elastometric measures. Receiver operating characteristic curve analysis of GLQ performance using vibration-controlled transient elastography as a reference yielded areas under the curves of 0.851 for F ≥ F1, 0.793 for F ≥ F2, 0.784 for F ≥ F3 and 0.789 for F ≥ F4. GLQ has the potential to be a rapid, easy-to-perform and tolerable method in the staging of liver fibrosis.

Effect of a common missense variant in LIPA gene on fatty liver disease and lipid phenotype: New perspectives from a single-center observational study.

Lysosomal acid lipase deficiency (LAL-D) is an autosomal recessive disease characterized by hypoalphalipoproteinemia, mixed hyperlipemia, and fatty liver (FL) due to mutations in LIPAse A, lysosomal acid type (LIPA) gene. The rs1051338 single-nucleotide polymorphism (SNP) in LIPA gene, in vitro, could adversely affect the LAL activity (LAL-A). Nonalcoholic fatty liver disease (NAFLD) is often associated with metabolic syndrome, and the diagnosis requires the exclusion of excess of alcohol intake and other causes of hepatic disease. The aim of the study was to evaluate the impact of rs1051338 rare allele on lipid phenotype, severity of FL, and LAL-A in patients suffering from dyslipidemia associated with NAFLD. We selected 74 subjects with hypoalphalipoproteinemia or mixed hyperlipemia and evaluated transaminases, liver assessment with controlled attenuation parameter (CAP), LAL-A, rs1051338 SNP genotype. The presence of rare allele caused higher levels of triglycerides and hepatic transaminase and lower levels of high-density lipoprotein cholesterol (HDL-C). Multivariate analysis highlighted independent association between rare allele and FL severity in subjects with NAFLD. The rs1051338 SNP may modulate FL severity and atherogenic dyslipidemia in patients suffering from NAFLD.

Real-world experience with obeticholic acid in patients with primary biliary cholangitis.

BACKGROUND & AIMS: Obeticholic acid (OCA) is the second-line treatment approved for patients with primary biliary cholangitis (PBC) and an inadequate response or intolerance to ursodeoxycholic acid. We aimed to evaluate the effectiveness and safety of OCA under real-world conditions. METHODS: Patients were recruited into the Italian PBC Registry, a multicentre, observational cohort study that monitors patients with PBC at national level. The primary endpoint was the biochemical response according to Poise criteria; the secondary endpoint was the biochemical response according to normal range criteria, defined as normal levels of bilirubin, alkaline phosphatase (ALP), and alanine aminotransferase (ALT) at 12 months. Safety and tolerability were also assessed. RESULTS: We analysed 191 patients until at least 12 months of follow-up. Median age was 57 years, 94% female, 61 (32%) had cirrhosis, 28 (15%) had histologically proven overlap with autoimmune hepatitis (PBC-AIH). At 12 months, significant median reductions of ALP (-32.3%), ALT (-31.4%), and bilirubin (-11.2%) were observed. Response rates were 42.9% according to Poise criteria, and 11% by normal range criteria. Patients with cirrhosis had lower response than patients without cirrhosis (29.5% vs. 49.2%, p = 0.01), owing to a higher rate of OCA discontinuation (30% vs. 12%, p = 0.004), although with similar ALP reduction (29.4% vs. 34%, p = 0.53). Overlap PBC-AIH had a similar response to pure PBC (46.4% vs. 42.3%, p = 0.68), with higher ALT reduction at 6 months (-38% vs. -29%, p = 0.04). Thirty-three patients (17%) prematurely discontinued OCA because of adverse events, of whom 11 experienced serious adverse events. Treatment-induced pruritus was the leading cause of OCA discontinuation (67%). CONCLUSIONS: Effectiveness and safety of OCA under real-world conditions mirror those in the Poise trial. Patients with cirrhosis had lower tolerability. Overlap PBC-AIH showed higher ALT reduction at 6 months compared with patients with pure PBC. LAY SUMMARY: Obeticholic acid (OCA) was shown to be effective in more than one-third of patients not responding to ursodeoxycholic acid in a real-world context in Italy. Patients with cirrhosis had more side effects with OCA, and this led to suspension of the drug in one-third of patients. OCA was also effective in patients who had overlap between autoimmune hepatitis and primary biliary cholangitis.

Elevations in alanine aminotransferase levels late in the course of antiviral therapy in hepatitis C virus RNA-negative patients are associated with virological relapse.

UNLABELLED: The incidence and clinical meaning of elevated alanine aminotransferase (ALT) in chronic hepatitis C patients who are hepatitis C virus (HCV)-RNA negative during pegylated interferon (PEG-IFN) and ribavirin therapy have not been completely characterized. In this study our aim was to assess the incidence, pattern, predictive factors, and clinical meaning of elevated ALT in a cohort of 173 chronic hepatitis C patients who obtained viral clearance during either PEG-IFNalpha2(a) or alpha2(b) and weight-based ribavirin therapy. Patients were defined sustained viral responders (SVRs) or relapser responders (RRs) on the basis of a serum HCV-RNA result at 24-week follow-up. SVR and RR were obtained in 141 (58%) and 32 patients (13%), respectively. Among the 173 study patients, 57 patients (33%) had undetectable serum HCV-RNA and elevated ALT in at least one evaluation (weeks 2, 4, 12, 24 in all genotypes, and week 48 in HCV genotype 1 and 4 alone), and this phenomenon was not differently distributed between SVRs and RRs. No pretreatment demographic (age, gender), clinical (ALT levels, histological grade and stage, body mass index) and viral (load, genotype) parameter was associated with this phenomenon. The incidence of elevated ALT levels was not associated with type of PEG-IFN and ribavirin dose. Elevated ALT levels showed a different longitudinal pattern, occurring more frequently between week 12 and the end of treatment in RR as compared to SVR patients (90% versus 9%, P = 0.000001). CONCLUSION: The occurrence of elevated ALT levels in HCV-RNA-negative patients during PEG-IFN and ribavirin therapy is a fairly frequent and unpredictable phenomenon. Although ALT elevation per se is not associated with a greater risk of relapse, its occurrence in the later phases of therapy is more common in relapsing patients.

Predictive factors for response to peginterferon-alpha and ribavirin treatment of chronic HCV infection in patients aged 65 years and more.

BACKGROUND: Elderly patients with chronic hepatitis C virus (HCV) infection represent an understudied population, and little is known regarding the predictive factors for sustained virological response (SVR) to antiviral therapy in these patients. AIMS: To evaluate the efficacy of pegylated interferon (PEG-IFN) and ribavirin therapy in chronic HCV patients aged 65 years, and identify pre- and on-treatment predictors of SVR. METHODS: We studied 57 patients aged ≥65 years who underwent PEG-IFN and ribavirin treatment, evaluating the SVR rate and its association with pre-treatment demographic, clinical, biochemical, and virological parameters. Furthermore, we assessed whether 12-week serum HCV-RNA assessment might predict SVR. RESULTS: A SVR was obtained in 25 patients (45%). The only pre-treatment predictor of SVR was HCV genotype 2 and 3 (P = 0.02). A positive serum HCV-RNA or a decline in viral load ≤2log(10) at week 12 had 100% negative predictive value for SVR. No major liver-related events or deaths occurred during therapy. Treatment was discontinued due to side effects-mainly cardiovascular-in 10 patients (17%). CONCLUSION: Pre- and on-treatment virological parameters can be used to identify elderly patients who are more likely to obtain a SVR to standard-of-care antiviral therapy for chronic HCV infection.

Strengthening of Wood-Like Materials via Densification and Nanoparticle Intercalation.

Recently, several chemical and physical treatments were developed to improve different properties of wood. Such treatments are applicable to many types of cellulose-based materials. Densification leads the group in terms of mechanical results and comprises a chemical treatment followed by a thermo-compression stage. First, chemicals selectively etch the matrix of lignin and hemicellulose. Then, thermo-compression increases the packing density of cellulose microfibrils boosting mechanical performance. In this paper, in comparison with the state-of-the-art for wood treatments we introduce an additional nano-reinforcemeent on densified giant reed to further improve the mechanical performance. The modified nanocomposite materials are stiffer, stronger, tougher and show higher fire resistance. After the addition of nanoparticles, no relevant structural modification is induced as they are located in the gaps between cellulose microfibrils. Their peculiar positioning could increase the interfacial adhesion energy and improve the stress transfer between cellulose microfibrils. The presented process stands as a viable solution to introduce nanoparticles as new functionalities into cellulose-based natural materials.

High-current stream of energetic α particles from laser-driven proton-boron fusion.

The nuclear reaction known as proton-boron fusion has been triggered by a subnanosecond laser system focused onto a thick boron nitride target at modest laser intensity (∼10^{16}W/cm^{2}), resulting in a record yield of generated α particles. The estimated value of α particles emitted per laser pulse is around 10^{11}, thus orders of magnitude higher than any other experimental result previously reported. The accelerated α-particle stream shows unique features in terms of kinetic energy (up to 10 MeV), pulse duration (∼10 ns), and peak current (∼2 A) at 1 m from the source, promising potential applications of such neutronless nuclear fusion reactions. We have used a beam-driven fusion scheme to explain the total number of α particles generated in the nuclear reaction. In this model, protons accelerated inside the plasma, moving forward into the bulk of the target, can interact with ^{11}B atoms, thus efficiently triggering fusion reactions. An overview of literature results obtained with different laser parameters, experimental setups, and target compositions is reported and discussed.

Clinical and virological survey of patients with hepatitis B surface antigen in an Italian region: clinical considerations and disease burden.

The aim of this study was to determine the prevalence of hepatitis B virus (HBV) infection in an Italian region, Liguria (1,572,000 inhabitants), by means of a network of 12 referral centers for liver diseases. All patients with HBV surface antigen followed throughout 2006 were included. Personal data, infectious status with risk factors, other non-infectious risk factors for liver disease, clinical status, and treatment were the questionnaire. Four hundred forty-five patients (71% male) were evaluated. Their median age was 48 years (range 5-84), and 83.4% were of Italian origin. Community-acquired infection was the principal mode of HBV transmission (82.5%), followed by previous intravenous drug use (9.4%), perinatal transmission (6.3%), and transfusion-associated transmission (1.8%). Hepatitis B e-antigen was present in 20.4% of the patients, while co-infections with hepatitis D virus and/or hepatitis C virus and/or human immunodeficiency virus (HIV) were observed in 18.7% of the patients. Chronic active hepatitis was present in 62.5% of the patients, cirrhosis in 13.5%, hepatocellular carcinoma in 2.2%, and 21.8% of the patients were inactive carriers of HBV. In all, 42.5% of the patients were treated with interferon or lamivudine and/or adefovir-dipivoxil. Forty-nine patients were co-infected with HIV (86% on highly active antiviral therapy). Nevertheless, this study identified only 2.2% of the expected patients with HBV. Hence, it has to be reasoned that few potential infectious or treatable patients are referred to liver disease centers. HBV infection is still an underestimated health problem, and few potential infectious or treatable patients are referred to tertiary centers.