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Allergic contact dermatitis caused by (meth)acrylates is well known, both in occupational and in non-occupational settings. Contact hypersensitivity to electrocardiogram (ECG) electrodes containing (meth)acrylates is rarely reported.To report the first case of contact dermatitis caused by acrylic acid impurity in ECG electrodes.Patch tests were performed with separate components of electrodes and some (meth)acrylates. This was followed by high-performance liquid chromatography of electrode hydrogel.The patient was contact-allergic to electrode hydrogel but not to its separate constituents. Positive reactions were observed to 2-hydroxyethyl methacrylate (2-HEMA), 2-hydroxypropyl methacrylate (2-HPMA) and ethyleneglycol dimethacrylate (EGDMA). Subsequent analysis showed that the electrode hydrogel contained acrylic acid as an impurity. The latter was subsequently patch tested, with a positive result.The sensitization resulting from direct contact with ECG electrodes was caused by acrylic acid, present as an impurity in ECG electrodes. Positive reactions to 2-HEMA, 2-HPMA and EGDMA are considered to be cross-reactions.

Serial liver biopsies are the gold standard by which the progression of fibrosis is evaluated. This longitudinal cohort study assessed the different rates in the progression of fibrosis using serial liver biopsies and serum fibrosis markers YKL-40 and PIIINP and the cytokines, transforming growth factor beta (TGF-beta) and tumor necrosis factor alpha (TNuF-alpha). A 10-year cohort study was performed in patients with hepatitis C virus (HCV) alone or HCV and schistosomiasis. Patients were enrolled at the time of acute HCV infection and prospectively evaluated with two liver biopsies (at entry and end of follow-up), and true rates in the progression of fibrosis were calculated per year. Serum YKL-40, N-terminal propeptide of collagen III (PIIINP), TGF-beta, and TNF-alpha were measured, as well as the expression of TGF-beta, TNF-alpha, and YKL-40 mRNA in liver tissue. A significant increase in the progression rates of fibrosis occurred in the coinfected group (0.61 +/- 0.13) compared with the HCV monoinfection group (0.1 +/- 0.06; P < .001)). The progression of fibrosis rate/year had a direct linear correlation for YKL-40 (r = 0.892, P < .001) and for PIIINP (r = 0.577, P < .01). YKL-40 showed a linear correlation with TGF-beta (r = 0.897, P < .001). Hepatic mRNA levels of YKL-40 and TGF-beta correlated with the serum levels, confirming a hepatic source for the elevated serum levels. In conclusion, serial cytokine and fibrosis markers can accurately determine the rate at which fibrosis is progressing, identifying both those with rapid fibrosis and those with stable disease.

In order to evaluate the effects of mammary health status and lactation phase on the qualitative parameters of ovinemilk, 213 individual milk samples were repeatedly collected from 40 primiparous Sarda ewes on a monthly basis. Yield,physico-chemical characteristics, casein fractions quantitative distribution, somatic cell count (SCC), cheese making propertiesand plasmin-plasminogen activity were determined on each sample. Repeated individual milk SCC were used as amarker of udder health status, allowing the definition of three classes: “Healthy” (H), “Infected” (I) or “Doubtful” (D).Samples were grouped into 4 classes of days in milk (DIM). To evaluate the influence of mammary health status andphase of lactation, a mixed model was performed using the ewe as random effect. Milk physico-chemical parameters wereinfluenced both by the udder health status and by lactation phase. In particular, the udder health status adversely affectedαs1 and β1-casein fractions (Pand 64.60% in “H”, “D” and “I,” respectively. Lactation phase influenced the overall milk composition and technologicalcharacteristics. Plasmin activity was higher in the “I” group than in the others (16.1 vs 11.8 and 11.2 U/ml; Pit significantly (Pexert a detrimental effect on milk quality since they enhance its endogenous proteolytic activity.

Nodular regenerative hyperplasia (NRH) of the liver is a local hyperplastic response of hepatocytes, probably due to vascular abnormalities. Since it was shown in a few case reports that NRH may be associated with antiphospholipid antibodies (APA) we wanted to analyze the relevance of APA in patients with this disease. Sera from 13 patients with histologically defined NRH were tested for APA by an in-house ELISA using as antigens cardiolipin (CL), beta2-glycoprotein I (beta2-gp I), phosphatidylserine (PS), and thromboplastin (TP), a mixture of different phospholipids and phospholipid-binding proteins. As controls, sera from patients with serologically and histologically defined autoimmune liver diseases (primary biliary cirrhosis n = 14; autoimmune hepatitis n = 14) without histological evidence for NRH as well as from 14 healthy blood donors were analyzed. 77% of the NRH patients had APA. In 46% they were directed against CL. In contrast, only 14% of the patients with autoimmune liver diseases and 14% of the healthy controls had anti-CL antibodies (p0,05). Antibodies to beta2-gp I and TP did not discriminate between NRH and autoimmune liver diseases. Anti-PS antibodies were not observed. These data indicate that determination of anti-CL antibodies in NRH may help to identify a subgroup of patients in whom an 'organ-specific antiphosholipid syndrome' of the liver may be involved in the pathogenesis.

We report about a 66-year-old-male patient who was hospitalized with generalized exanthema and increase of liver enzymes after intake of metamizole because of flue-like symptoms. Despite initial high dose steroids, disease activity persisted, and therefore liver biopsy was performed. Histology revealed acute hepatitis with perivenular non-bridging confluent necrosis and granuloma formation consistent with drug-induced hepatitis. A metamizole-induced process was suspected. Lymphocyte transformation test confirmed the sensitization of the patient's lymphocytes to metamizole and three of its four metabolites (4-methylaminoantipyrine, 4-acetylaminoantipyrine and 4-formylaminoantipyrine). Other drugs could be excluded with high probability. In the follow-up, the general condition of the patient improved, and liver enzymes decreased under treatment with steroids. Thus, we conclude that in this patient metamizole has induced an allergic reaction not only of the skin but also of the liver. To our knowledge, an allergic cholestatic hepatitis caused by metamizole has been reported only once in literature.

In this article we conduct an empirical analysis of daily log-returns of Italian open-end mutual funds and their respective benchmarks in the period from February 2007 to May 2015. First, we estimate the classical normal-based model on the log-returns of a large set of funds. Then we compare it with five models allowing for asymmetry and (or) heavy tails. We empirically assess that both the value at risk and the average value at risk are model-dependent and we show that the difference between models should be taken into consideration in the evaluation of risk measures.

Background: Skin toxicity is frequent and debilitating in oncologic patients treated with epidermal growth factor receptor inhibitors (EGFRIs). Grading and management of skin adverse events (AEs) are poorly standardized. Materials and Methods: We developed a new score (EGFRISTI: Epidermal Growth Factor Receptor Inhibitor-Related Skin Toxicity Index) which is able to quantify and monitor all EGFRI-related dermatologic AEs over time. The utility of this tool was validated in 130 patients treated with 5 different EGFRIs including both monoclonal antibodies and tyrosine kinase inhibitors. Results: The mean baseline EGFRISTI score was 26.9 (range: 6.0-64.5). Mild toxicity was found in 55 patients (42.3%), moderate toxicity in 43 (33.1%), and severe toxicity in 32 patients (24.6%). After the first-line toxicity treatment, an EGFRISTI score reduction of >75% was obtained in 31 patients (34.1%) and one of 50% in 40 patients (43.9%), while an improvement of Conclusions: The EGFRISTI is a simple and reliable tool to quantify and express the severity of all clinical signs and symptoms of EGFRI skin toxicity with a single numerical value, to choose the most suitable therapy, and to measure its efficacy.

The prevalence of occupational and non-occupational textile dermatitis seems to be increasing, probably because of changed textile manufacturing techniques.Evaluation of the clinical features and epidemiology of textile contact dermatitis (TCD) in Italy.Demographic data, clinical history aspects, atopy and positive patch test reactions to occupational and non-occupational allergens were investigated in 277 textile dermatitis patients.Contact dermatitis was the most frequent clinical presentation (95.3%). TCD was more common in females, in the fourth to fifth decades of life, and in atopic dermatitis patients. The lesions were prevalently eczematous (74.2%), and mostly located on the trunk and lower limbs in non-occupational cases, and on the hands in textile workers. Allergic TCD (58.3%) was more frequent than irritant TCD. The dyes (Disperse Blue 124, Disperse Blue 106, and Disperse Yellow 3) were most frequently responsible (79.8%), especially in non-occupational TCD. Formaldehyde and resins were more important in occupational TCD. Concomitant reactions among textile dyes and/or finishing resins were observed in 50.0% of patients.Some strategies (sensitization potential of new textile chemicals, more stable dyes, reduced levels of formaldehyde in clothing, and collaboration with textile industry and trade associations) should be adopted to decrease the TCD incidence and update the textile patch testing series.

In this paper we consider several time-varying volatility and/or heavy-tailed models to explain the dynamics of return time series and to fit the volatility smile for exchange-traded options where the underlying is the main �Borsa Italiana� stock index. Given observed prices for the time period we investigate, we calibrate both continuous-time and discrete-time models. First, we estimate the models from a time-series perspective (i.e. under the historical probability measure) by investigating more than ten years of daily index price log-returns. Then, we explore the risk-neutral measure by fitting the values of the implied volatility for numerous strikes and maturities during the highly volatile period from April 1, 2007 (prior to the subprime mortgage crisis in the U.S.) to March 30, 2012. We assess the extent to which time-varying volatility and heavy-tailed distributions are needed to explain the behavior of the most important stock index of the Italian market.

Background & Aims: Immune responses during the first few months of acute hepatitis C virus (HCV) infection seem crucial for viral control, but the relationship of these responses to natural history is poorly characterized. Methods: This prospective study investigated the HCV-specific CD4 + and cytokine responses in patients with acute HCV hepatitis with or without Schistosoma mansoni coinfection, a parasitic infection with T helper (Th) 2 immune bias. HCV-specific CD4 + proliferative responses and cytokine production in peripheral blood mononuclear cells were correlated with liver biopsy results at 6 months and at the end of follow-up. Results: Whereas 5 of 15 patients with HCV alone recovered from acute HCV, all (17 of 17) patients with S. mansoni coinfection progressed to histologically proven chronic hepatitis. Coinfected patients had either absent or transient weak HCV-specific CD4 + responses with Th0/Th2 cytokine production. The magnitude of the HCV-specific CD4 + response at week 12 was inversely correlated with the fibrosis progression rate in chronically infected patients. Conclusions: Patients with acute hepatitis C and schistosomiasis coinfection cannot clear viremia and show rapid progression once chronic infection is established. This rapid progression is associated with a strong Th2 response in peripheral immune responses, suggesting that early development of vigorous Th1 responses not only facilitates clearance but delays disease progression. GASTROENTEROLOGY 2001;121:646-656

We retrospectively studied 42 liver biopsy specimens from 39 patients who met serologic and histologic criteria of autoimmune liver diseases. We found 10 cases of overlap syndrome (OLS), 10 autoimmune cholangitis (AIC), 10 primary biliary cirrhosis (PBC), and 9 autoimmune hepatitis (AIH) type 1. The following results were obtained: (1) Granulomas and biliary duct lesions were more prominent in PBC and AIC than in OLS and AIH. (2) Bile duct loss was not observed in AIH cases. (3) Features of hepatocellular damage such as piecemeal necrosis, spotty lobular necrosis, and confluent necrosis, were much more prevalent in OLS and AIH than in PBC and AIC. (4) HLA-DR antigen expression by hepatocytes was more frequent in AIH and OLS, whereas the expression of the same antigen by the bile duct epithelium was more frequent in PBC and AIC. We conclude there is a morphologic spectrum in autoimmune liver diseases, in which PBC forms one end of the spectrum, AIH the other, OLS the middle but closer clinically and histologically to AIH than to PBC, and AIC, which seems to be an antimitochondrial antibody-negative subtype of PBC.

Background/ Aims: Infection with Schistosoma mansoni is endemic in Egypt leading to hepatic schistosomiasis and eventually portal hypertension. The prevalence of antibodies against hepatitis virus C among Egyptians is 14-51%. The aim of the present study was to investigate the influence of schistosomiasis on chronic hepatitis C with respect to the natural course of the disease, immunology, virology and histology. Patients and Methods: One hundred and twenty-six Egyptian patients classified into three groups: group A: chronic hepatitis C (n=33); group B: chronic schistosomiasis (n=30) and group C: chronic hepatitis C and chronic schistosomiasis (n=63) were enrolled and prospectively followed for 62.7±22 months. Patients infected with other hepatic viruses and/or parasites were excluded. Detailed history, clinical examination, CD4 + and CD8 + lymphocyte counts in blood, hematological and blood chemical values, abdominal ultrasonography, upper endoscopy, HCV RNA titer by RT/PCR, genotype and histological activity index in the liver biopsy were determined. Results: Thirty patients (48%) with HCV and schistosomiasis had liver cirrhosis and Child-Pugh class C vs. five (15%) in HCV patients and none in the schistosomal group. HCV RNA levels ranged between 0.07 and 13×10 5 copies/ml in group A, and between 1 and 25×10 5 copies/ml in group C. HCV genotype 4 was detected in 58 patients with co-infection (92%) and 21 patients with HCV alone (64%). Patients with coinfection showed higher grading and staging scores in their liver biopsies. Hepatocellular carcinoma was detected only in patients with coinfection. During follow-up, the mortality rate was 12%, 3% and 48% in group A, B and C, respectively. Conclusions: Patients with concomitant HCV and schistosomiasis infection were characterized by more advanced liver disease, higher HCV RNA titers, predominance of HCV genotype 4, higher histologic activity, higher incidence of cirrhosis and hepatocellular carcinoma as well as a much higher mortality rate.

In 1983, a female patient born in 1963 presented with symptoms of ulcerative colitis and typical clinical and histological signs of primary sclerosing cholangitis (PSC). At this time only pANCA were positive while other marker antibodies for autoimmune liver disorders could not be detected. In summer 1987 the clinical picture changed and was replaced by laboratory and histological signs typical of autoimmune hepatitis (AIH). Thus, IgG levels increased considerably and cholestatic enzymes became normal. For the first time, anti-liver-pancreas antibodies (LP), a diagnostic marker for AIH type III could be detected. In the following years several relapses occurred also induced by repeated discontinuation of immunosuppressive therapy. Symptoms of colitis persisted but signs of cholestasis remained absent for the following ten years. In 1997, colitis exacerbated again and colectomy had to be performed together with liver transplantation. Surprisingly, histology of the explanted liver now showed the typical features of PSC stage III/IV while the significant criteria for AIH were now lacking. Thus, progression to cirrhosis was, probably, mainly induced by the biliary destructive and fibrotic process although biochemical and serological data were clearly indicative of an autoimmune, i.e. AIH-related manifestation.

Hepatocellular carcinoma (HCC) is one of the most common neoplasms worldwide. Well-established risk factors include infections with two very different viruses: the DNA virus causing hepatitis B (HBV) and the RNA virus inducing hepatitis C (HCV). In order to determine whether genetic differences exist between HBV- and HCV-induced HCC, 41 HCC samples of known vival status were examined by comparative genomic hybridization (CGH). The analysis revealed frequent deletions of 1p (24%), 4q (39%), 6q (41%), 8p (44%), 9p (24%), 11q (24%), 12q (22%), and 13q (39%), as well as common gains of 1q (46%), 6p+ (20%), 8q+ (41%), 11q (27%), and 17q+ (37%). There was no significant difference in the number and type of chromosomal imbalances between 25 HCV- and 16 HBV-infected tumours. This is consistent with models suggesting that HBV and HCV cause cancer through non-specific inflammatory and regenerative processes, rather than through virus-specific interactions with defined target genes. Chromosomal imbalances were also unrelated to the grade and stage of HCC. This may suggest that most gross genomic alterations occur early during HCC development and that further progression of these tumours may be associated with other types of genetic changes, not detectable by CGH. In summary, these data show that characteristic gross genomic changes occur in HCC, but these alterations at present do not appear to have diagnostic or prognostic applications.

With the advent of genome analysis and developments in proteomic tools, search for milk protein polymorphisms has exploded and progressively moved from qualitative to quantitative aspects. A great diversity of alleles have been discovered at the six main milk protein loci and significant advances made in understanding the relationship between nucleotide polymorphisms and protein structure and expression. Some demonstrative examples, taken in cattle and goats, will be addressed to illustrate how mutations responsible for polymorphisms at the genomic level can influence milk protein composition, both qualitatively and quantitatively. Although milk fat globule membrane-associated proteins account for only 1–2 % of total milk proteins, evidence that these proteins possess techno-functional and nutritional properties is accumulating and data on their genetic polymorphisms are becoming more consistent. A part of this chapter is also devoted to this issue.

We study the one-dimensional Ornstein-Uhlenbeck (OU) processes with marginal law given by the tempered stable and tempered infinitely divisible distributions proposed by Rosinski (2007) and Bianchi et al. (2010b), respectively. In general, the use of non-Gaussian OU processes is impeded by difficulty in calibration and simulation. Accordingly, we investigate the law of transition between consecutive observations of OU processes and – with a view to practical applications – evaluate the characteristic function of integrated tempered OU processes in three cases: classical tempered stable, variance gamma, and rapidly decreasing tempered stable. Then we analyze how one can draw a random sample from this class of processes using both the classical inverse transform algorithm and an acceptance-rejection method based on the simulation of a stable random sample. Finally, with a maximum likelihood estimation method based on the fast Fourier transform, we assess the performance of the simulation algorithm empirically.

Background/Aim: Interferon has become the mainstay of treatment of chronic hepatitis C; however, duration of treatment and dose remain unresolved questions. The present study aimed to compare standard dose interferon with a titrated dose regimen carried out for 1 year. Methods: This was a randomized, controlled multicenter trial. Patients with chronic hepatitis C were randomly allocated to a control group ( n =30), to a fixed dose group ( n =31) where interferon-α 2b 3 MU thrice weekly was given for 1 year or a titrated group ( n =34) where interferon was titrated starting at 5 MU thrice weekly to the lowest dose keeping the patient in remission as assessed by a normal ALT value. Liver biopsies were obtained before and at the end of treatment; in addition, galactose elimination capacity was measured as a measure of cytosolic function. Results: In the control, fixed an titrated groups a complete response was achieved in 229, 1028 and 1531, respectively ( p p =n.s. for the two treatments). The corresponding figure for sustained response was 129, 528 and 631 ( p =n.s.). In the titrated group, a complete (sustained) response was achieved with 5 MU in 2 (2), with 4 MU in 1 (0), with 3 MU in 4 (0), with 2 MU in 3 (0) and with 1 MU in 5 (4). Liver biopsy score and galactose elimination capacity improved significantly in responders but not in treatment failures. Conclusions: Both fixed and titrated dosing of interferon given for 1 year induced virus clearance in only a minority of treated patients. However, in a small number of patients, a complete and sustained response can be achieved with low doses of interferon. Dose titration could be an interesting approach to decreasing the cost and side effects in the treatment of chronic hepatitis C.

The current price of an option is obtained by the conditional expectation of the payoff function under the risk-neutral measure. The risk-neutral measure is the measure equivalent to the real market measure under which the discounted price process of the underlying stock becomes a martingale. In the Black-Scholes model, the risk-neutral measure can be obtained by the Girsanov theorem. The Esscher transform has been used to find the risk-neutral measure for the continuous Levy process models. The general theory of the Esscher transform is applied to find the risk-neutral measure under tempered stable Levy process models.

The dynamic of a financial asset's returns and prices can be expressed using a deterministic process if there is no uncertainty about its future behavior, or with a stochastic process in the more likely case when the value is uncertain. Stochastic processes in continuous time are the most used tool to explain the dynamics of a financial asset's returns and prices. They are the building blocks with which to construct financial models for portfolio optimization, derivatives pricing, and risk management. Continuous-time processes allow for more elegant theoretical modeling compared to discrete-time models and many results proven in probability theory can be applied to obtain a simple evaluation method. Keywords: Brownian motion; Poisson process; jump processes; Levy processes; stochastic process X =; gamma process; exponential process; variance gamma; process; stable process; standard CTS process; generalized tempered stable; process; modified tempered stable; process; standard MTS process; normal tempered stable; process; standard NTS process; normal inverse Gaussian; standard NIG process; Kim-Rachev tempered stable; standard KRTS process; rapidly decreasing tempered stable; standard RDTS process; Brownian motion; Independent increments; Stationary increments; time-changed Brownian motion; The Modified Tempered Stable Processes with Application to Finance; conditional expectation; change of measure; Esscher transform; Brownian Motion and Stochastic Calculus; Risk Assessment Decisions in Banking and Finance

In this paper, we study a model that captures four stylized facts about multivariate financial time series of equity returns: heavy tails, negative skew, asymmetric dependence, and volatility clustering (the four horsemen). The model is based on the multivariate normal tempered stable (MNTS) distribution, defined as the normal mean-variance mixture with a univariate tempered stable mixing distribution. To estimate the model, we propose a simple expectation–maximization maximum likelihood estimation procedure combined with the classical fast Fourier transform. The estimation algorithm is numerically reliable, and can be potentially used with a large number of assets. The method is applied to fit a five- and a 30-dimensional series of stock returns and to evaluate widely known portfolio risk measures. We analyzed the MNTS model with and without modeling the volatility clustering effect and compare the results with different models based on the multivariate normal and the multivariate generalized hyperbolic model.

La diagnosi di reazione avversa a farmaci (RAF) della cute e/o delle mucose non e in genere agevole, soprattutto in eta pediatrica. La ragione di cio e da ricercare nel fatto che la diagnosi e spesso retrospettiva, e eminentemente clinica e impone conoscenze dermatologiche consolidate. Le manifestazioni cutaneo-mucose, infatti, sono numerose, assai variegate e poco peculiari, salvo nei casi di eritema fisso, argiria e, forse, sindrome di Stevens- Johnson (Fig. 26.1) e necrolisi epidermica tossica. Le procedure clinico-anamnestiche, infine, dovrebbero essere condivise, al fine di uniformare le valutazioni epicrisiche. Cio permetterebbe, tra l’altro, un confronto piu costruttivo dei risultati degli studi epidemiologici. Open image in new window Fig. 26.1 Sindrome di Stevens-Johnson da fenitoina sodica

Fifty-six patients with biopsy-proven, chronic active hepatitis B were included in a multi-center, randomized trial comparing steroid withdrawal followed by 1.5 MU recombinant interferon alpha 2b (Intron ® ) with placebo withdrawal followed by either 1.5 or 5 MU interferon. The patients were equally distributed between the treatment groups with respect to biochemical and histologic activity as well as with respect to DNA levels and quantitative liver function tests. One patient was lost to follow up. After 1 year of treatment, 10/18, 13/19 and 11/18 patients had lost hepatitis B virus DNA in the three groups, respectively (non-significant). Transaminase levels were normal in 27/34 of the responders but in only 4/21 of the non-responders ( p

The patterns of cytokeratin as determined by murine monoclonal antikeratin antibody lu-5 (mAb lu-5) were quantitated in paraffin-embedded liver tissue from normal and diseased subjects. In tissue from healthy medical students, mAb lu-5 was found to decorate 2–4 periportal and 2–3 perivenular cell layers. Alcoholic liver disease was accompanied by a marked increase in intensity of mAb lu-5 antigen expression in zone I and III hepatocytes. Moreover, additional liver cells of both zones were progressively recruited, so that in advanced lesions all three lobular zones became positive. In mechanical as well as in drug-induced cholestasis, a similar increase of mAb lu-5 antigen expression was already observed in earlier stages of disease, including an earlier recruitment of zone II hepatocytes. In both alcoholic and cholestatic biopsies the intensity and extent of mAb lu-5 epitope expression increased with the duration and severity of disease. In primary biliary cirrhosis (PBC) and seemingly also in primary sclerosing cholangitis the increase and extent was more marked in zone I, the zone of assumed cholate accumulation. Changes in zone III, the territory of histologic cholestasis (bilirubinostasis), became evident only in late stages of PBC. Mallory bodies of alcoholic and cholestatic liver disease showed an identical mAB lu-5 antigen expression, thus giving rise to four different staining patterns. Changes of cytokeratin expression are similar in alcoholic and cholestatic liver diseases. In chronic viral hepatitis, however, cytokeratin alterations are discrete and restricted to precirrhotic/cirrhotic stages.

Most of the important models in finance rest on the assumption that randomness is explained through a normal random variable. However there is ample empirical evidence againstthe normality assumption, since stockreturns are heavy-tailed, leptokurtic and skewed. Partly in response to those empirical inconsistencies relative to the properties of the normal distribution, a suitable alternative distribution is the family of tempered stable distributions. In general, the use of infinitely divisible distributions is obstructed the difficulty of calibrating and simulating them. In this paper, we address some numerical issues resulting from tempered stable modelling, with a view toward the density approximation and simulation.

A RNA-PCR method and different sets of primers were used to investigate the expression of different hepatitis B (HB) virus genes at the RNA level. We tested paired samples (tumor and non-tumor) from the liver tissues of 48 Taiwanese patients with primary hepatocellular carcinoma (HCC). By using a set of primers which spanned the sequences of the S-gene, we found expression in only 2 patients. In one HBs-RNA was only detected in the tumor tissue and in the other only in the surrounding non-tumor tissue. Using primers covering the C-gene, expression was found in 7 patients. In 2 of these RNA was detected in both the tumor and the surrounding tissue, in 2 in the tumor tissue, and in 3 in the surrounding tissue only. Finally, when primers spanning the X-gene sequences were used, RNA was detected in 40/48 patients. In 33 of these cases HBx-RNA was detected in both tumor and non-tumor tissue, in 3 patients in tumor tissue only, and in 4 in the surrounding tissue. Among the cases in which HBc and HBs-RNA was expressed, all showed HBx expression also. These data indicate that the expression of the HBx gene in HCC may play an important role in hepatocarcinogenesis.

Structural alterations of liver parenchyma caused by ethinylestradiol, a synthetic estrogen known to induce cholestasis and to act as a tumor promoter factor, were investigated. Male rats treated with 17 alpha-ethinylestradiol (5 mg/kg body weight for 5 days) were compared with controls (n = 5 each). After perfusion fixation and systematic random sampling, paraffin sections, semithin sections and thin sections were examined observing standard stereological techniques. Ethinylestradiol treatment induced an increase in liver volume by 65% (p less than 0.001), which was caused more by hypertrophy (volume of singular hepatocyte +35%, p less than 0.001) than by hyperplasia (number of hepatocytes +23%, p less than 0.001). A decrease in sinusoidal membrane surface density (-43%, p less than 0.005) associated with a decrease in sinusoidal microvillar volume density (-50%, p less than 0.005) were both compensated for by the increase in liver volume. No canalicular alterations were observed. Thus changes in hepatocytes detectable with stereological techniques affect the sinusoidal pole where decreased sinusoidal membrane surface is associated with or reflects a substantial loss of membrane phospholipids. The increased liver volume may constitute an adaptive response compensating for the relative decrease in sinusoidal membrane surface and displays characteristics comparable to those of preneoplastic hepatocytes.

The polymerase chain reaction (PCR) was used to analyse tissues from paraffin blocks of liver needle biopsies retrospectively. Biopsies of 29 patients with proven HBsAg and HBcAg expression in liver tissue and of 8 healthy volunteers served as positive (group 1) and negative tissue controls (group 2), respectively. These were compared with 16 patients with proven HBsAg expression in liver but lack of HBcAg (group 3), with 23 patients with anti-HBc as the only hepatitis B virus (HBV)-related marker (group 4) and with 21 patients with liver disease and without HBV markers in tissue or serum (group 5). PCR detected HBV sequences in all cases of the positive control group and in 94% of group 3, in 65% of group 4, and in 71.4% of group 5, whereas all healthy volunteers were negative. Our data show that PCR is able to detect HBV-DNA sequences in virtually all patients with active viral antigen expression but also in a high proportion of hepatitic patients who are silent for active HB but may or may not show signs of a contact with the HBV. Thus, PCR for HBV-DNA in paraffin sections might become a useful tool for identifying patients carrying HBV-DNA but not expressing HBV antigens.

In this paper we derive closed-form solutions for the cumulative density function and the average value-at-risk for five subclasses of the infinitely divisible distributions: classical tempered stable distribution, Kim-Rachev distribution, modified tempered stable distribution, normal tempered stable distribution, and rapidly decreasing tempered stable distribution. We present empirical evidence using the daily performance of the S&P 500 for the period January 2, 1997 through December 29, 2006.

Developments in the real-estate sector are of crucial importance for the business cycle and financial stability. This study analyses developments in the Italian housing market on the basis of both real and financial variables. Following the sharp contraction of the market during the financial crisis and the more general fall in economic activity, a few signals suggests that the recession in the housing market is easing somewhat. However, the degree of uncertainty remains considerable. In recent months the ratio between the flow of bad debts to total outstanding loans to households and construction firms has reached the highest levels since the beginning of the decade. The paper also investigates three issues of a more structural nature. First, it examines the performance and the regulatory framework of real-estate investment funds in Italy. Second, it analyses the main characteristics of the taxation of residential housing, with reference to ownership, rentals and transactions. Finally, the paper estimates the impact on residential house prices of the growing demand for housing services by immigrants.

In this paper, we will discuss a parametric approach to risk-neutral density extraction from option prices based on the knowledge of the estimated historical density. A flexible distribution is needed in order to find an equivalent change of measure and, at the same time, take into account the historical estimates. To this end, we introduce a new tempered stable distribution that we refer to as the KR distribution. Some properties of this distribution will be discussed in this paper, along with the advantages in applying it to financial modeling. Since the KR distribution is infinitely divisible, a Lelvy process can be induced from it. Furthermore, we can develop an exponential Levy model, called the exponential KR model, and prove that it is an extension of the Carr, Geman, Madan, and Yor (CGMY) model. The risk-neutral process is fitted by matching model prices to market prices of options using nonlinear least squares. The easy form of the characteristic function of the KR distribution allows one to obtain a suitable solution to the calibration problem. To demonstrate the advantages of the exponential KR model, we present the results of the parameter estimation for the S&P 500 Index and option prices.

Light-chain deposition disease (LCDD) is a multisystemic disorder associated with plasma cell dyscrasias and multiple myeloma. It is histologically characterized by the deposition of a homogeneous, in electron microscopy granular, slightly eosinophilic material showing positivity usually for kappa light chains. In contrast to AL-amyloidosis, the material is negative for Congo red. LCDD mainly involves the kidneys as the predominant organ manifestation resulting in a nephrotic syndrome. However, involvement of other tissues such as liver and heart have been described. Here we report a case of severe ischemic cholangitis in a patient with multiple myeloma receiving chemotherapy with melphalan, prednisone, and lenalidomide. Histopathological analysis revealed LCDD of the hepatic arteries as the underlying cause. This is to our knowledge the first case of LCDD of terminal liver arteries as a cause of intrahepatic ischemic cholangitis.

Basel III requires banks to include a credit value adjustment (CVA) into capital charges. Both CVA and debt value adjustment (DVA) must be included for derivatives using mark-to-market accounting. An effective method to calculate bilateral-CVA (BR-CVA) by incorporating wrong-way risk (WWR) for a collateralized counterparty is proposed which handles WWR — defined as when counterparty credit exposure increases as default probability increases — by building a trivariate Gaussian copula between the aggregate market risk exposure factor and default quality of the financial institution and counterparty. This paper extends the ordered-scenario copula model proposed in the literature. It links BR-CVA pricing and WWR, which is close to the current regulatory requirement and useful for managing a financial institution's risk. A practical example is provided. Numerical results suggest that the proposed method is efficient and robust and can easily stress test the impact of WWR in BR-CVA pricing.

Plus-strand RNA viruses characteristically replicate their genome in association with altered cellular membranes. In the present study, the capacity of hepatitis C virus (HCV) proteins to elicit intracellular membrane alterations was investigated by expressing, in tetracycline-regulated cell lines, a comprehensive panel of HCV proteins individually as well as in the context of the entire HCV polyprotein. As visualized by electron microscopy (EM), expression of the combined structural proteins core-E1-E2-p7, the NS3-4A complex, and protein NS4B induced distinct membrane alterations. By immunogold EM (IEM), the membrane-altering proteins were always found to localize to the respective altered membranes. NS4B, a protein of hitherto unknown function, induced a tight structure, designated membranous web, consisting of vesicles in a membranous matrix. Expression of the entire HCV polyprotein gave rise to membrane budding into rough endoplasmic reticulum vacuoles, to the membranous web, and to tightly associated vesicles often surrounding the membranous web. By IEM, all HCV proteins were found to be associated with the NS4B-induced membranous web, forming a membrane-associated multiprotein complex. A similar web-like structure in livers of HCV-infected chimpanzees was previously described (Pfeifer et al., Virchows Arch. B., 33: 233-243, 1980). In view of this finding and the observation that all HCV proteins accumulate on the membranous web, we propose that the membranous web forms the viral replication complex in HCV-infected cells.

In this study, we investigate two multivariate time-changed Brownian motion option pricing models in which the connection between the historical measure P and the risk-neutral measure Q is given by the Esscher transform. The models incorporate skewness, kurtosis and more complex dependence structures among stocks log-returns than the simple correlation matrix. The two models can be seen as a multivariate extension of the normal inverse Gaussian (NIG) model and the variance gamma (VG) model, respectively. We discuss two possible approaches to estimate historical asset returns and calibrate univariate option implied volatilities. While the first approach considers only time series of log-returns, the second approach makes use of both time series of log-returns and univariate observed volatility surfaces. To calibrate the models, there is no need of liquid multivariate derivative quotes.