Treatment of Recurrent Hepatitis C after Liver Transplantation with PEG-Interferon and Ribavirin.

Background and aim: Recurrent hepati tis C is a major cause of morbidity and mortality after li ver transpl ant ati on (LT), and optimal treatm ent algorithms have yet to be defined. Here, we present our experience of 22 patients with recurrent hepatitis C treated in our institution .Patients and methods: Twenty-two patients with hi stology-proven recurrent hepati tis Cafter LT were treated since 2003. Treatment was ini ti ated with pegylated interferon-a2a 135 IIg per week and ribavirin 400 mg per day in the majority of patients, and subsequent doses were adapted individllally based on on-treatment virologieal responses and c1inical and/or biochemical si de effeets.Results: On an intention-to-treat basis, ustained virological re ponse(SVR) was achieved in 12/21 (54.5%) patie nts (5/12 [41 .6%], 2/3 [67%], 4/5 [80%] and 1/2 [50%] of patients infected with genotypes 1,2,3 and 4, respectively). Two patients experieneed relap e and 6 did not respond to treatm ent (NR). Treatment duration ranged from 24 to 90 weeks. It was stopped prematurely due to adverse events in 6/22 (27.2%) patients (with SVR achieved in 2 patients, NR in 2 patients, and death of 2 patients: one patient awaiting retransplantation and a second patient with HCV-HJV co-infection and fibrosing cholestat ic hepatiti s, nine months after transplantation). Of note, SVR was achi eved in a patient \Vi th combined liver and kidney transplantation. Importantly, SVR \Vas ach ieved in some patients despite the lack ofan early virological response or HCV RNA negativity at week 24. Darbepoetin a and fil ~,'rasti m were used in 36% and 18%, respectively.Conclusion: Individually adapted treatment of recurrent hepatitis C canachieve SVR in a substantial proponion ofLT patients. Conventional stopping rules do not apply in this setting so that prolonged therapy may be useful in selected patients.

Price transmission and market power analysis in the Spanish seafood market chain

[cat] Espanya és un dels principals mercats de productes pesquers d’Europa i del món. El consum de productes pesquers ha estat tradicionalment molt important a Espanya, el 2005 es varen consumir 36,7 kg per persona (MAPA, diversos anys). Malgrat això, el mercat i cóm interactuen els diversos nivells de la cadena de comercialització han gaudit de poca atenció. En aquest estudi, utilitzant dades setmanals, s’analitza per als dotze principals productes pesquers, l’elasticitat en la transmissió de preus al llarg de la cadena de comercialització a Espanya (llotja, mercat central i detallista). Finalment s’investiga la presència d’assimetria en la transmissió de preus entre aquests nivells de mercat. Els resultats obtinguts tenen importants implicacions a l’hora d’analitzar la demanda, poder de mercat i marges al llarg del mercat per als productes pesquers.

Shallow-platform palaeoenvironmental conditions recorded in deep-shelf sediments: C and stable isotopes in Upper Jurassic sections of southern Germany (Oxfordian-Kimmeridgian)

A high-resolution carbon and oxygen isotope analysis of Late Oxfordian-Early Kimmeridgian deep-shelf sediments of southern Germany is combined with investigation of nannofossil assemblage composition and sedimentological interpretations in order to evaluate the impact of regional palaeoenvironmental conditions on isotopic composition of carbonates. This study suggests that carbonate mud was essentially derived from the Jura shallow platform environments and also that the isotopic signature of carbonates deposited in the Swabian Alb deep shelf indirectly expresses the palaeoenvironmental evolution of the platform. Short-term fluctuations in delta(13) C and delta(18)O are probably controlled by changes in salinity (fresh-water input versus evaporation) in platform environments. Long-term fluctuations in carbon and oxygen isotope record throughout the Late Oxfordian-Early Kimmeridgian result from the interplay of increasing temperature and decreasing humidity, which both control the trophic level. Changes from mesotrophic to oligotrophic conditions in platform environments and in the deep-shelf surface waters are inferred. During the Late Oxfordian (Bimammatum Subzone to Planula Zone), the delta(13)C curve displays a positive shift of about 1 parts per thousand, which is comparable in intensity to global perturbations of the carbon cycle. This evident isotopic shift has not been documented yet in other basinal settings. It can be reasonably explained by local palaeoenvironmental changes on the Jura platform (salinity, temperature, and nutrient availability) that controlled platform carbonate production, and the geochemistry of overlying waters. However, increasing carbonate production on the Jura platform and related positive delta(13)C shifts recorded in the Swabian Alb deep shelf are the regional signatures of climatic changes affecting other palaeogeographical domains of Europe in which the carbonate production increased throughout the Late Oxfordian. (C) 2002 Elsevier Science B.V. All rights reserved.

Caspofungin for prevention of intra-abdominal candidiasis in high-risk surgical patients.

PURPOSE: Thirty to forty percent of patients with recurrent gastrointestinal perforation/anastomotic leakage or acute necrotizing pancreatitis develop intra-abdominal invasive candidiasis (IC). A corrected Candida colonization index (CCI) > or =0.4 is a powerful predictor of IC. Fluconazole prevents intra-abdominal IC in this setting, but azole-resistant Candida species are emerging. The aim of this study was to explore the efficacy and safety of caspofungin for prevention of intra-abdominal IC in high-risk surgical patients. METHODS: Prospective non-comparative single-center study in consecutive adult surgical patients with recurrent gastrointestinal perforation/anastomotic leakage or acute necrotizing pancreatitis. Preventive caspofungin therapy (70 mg, then 50 mg/day) was given until resolution of the surgical condition. Candida colonization index and CCI, occurrence of intra-abdominal IC and adverse events were monitored. RESULTS: Nineteen patients were studied: 16 (84%) had recurrent gastrointestinal perforation/anastomotic leakage and 3 (16%) acute necrotizing pancreatitis. The median duration of preventive caspofungin therapy was 16 days (range 4-46). The colonization index decreased significantly during study therapy, and the CCI remained <0.4 in all patients. Caspofungin was successful for prevention of intra-abdominal IC in 18/19 patients (95%, 1 breakthrough IC 5 days after inclusion). No drug-related adverse event requiring caspofungin discontinuation occurred. CONCLUSION: Caspofungin may be efficacious and safe for prevention of intra-abdominal candidiasis in high-risk surgical patients. This needs to be further investigated in randomized trials.

Phylogeography and Pleistocene refugia of the adder (Vipera berus) as inferred from mitochondrial DNA sequence data.

In order to contribute to the debate about southern glacial refugia used by temperate species and more northern refugia used by boreal or cold-temperate species, we examined the phylogeography of a widespread snake species (Vipera berus) inhabiting Europe up to the Arctic Circle. The analysis of the mitochondrial DNA (mtDNA) sequence variation in 1043 bp of the cytochrome b gene and in 918 bp of the noncoding control region was performed with phylogenetic approaches. Our results suggest that both the duplicated control region and cytochrome b evolve at a similar rate in this species. Phylogenetic analysis showed that V. berus is divided into three major mitochondrial lineages, probably resulting from an Italian, a Balkan and a Northern (from France to Russia) refugial area in Eastern Europe, near the Carpathian Mountains. In addition, the Northern clade presents an important substructure, suggesting two sequential colonization events in Europe. First, the continent was colonized from the three main refugial areas mentioned above during the Lower-Mid Pleistocene. Second, recolonization of most of Europe most likely originated from several refugia located outside of the Mediterranean peninsulas (Carpathian region, east of the Carpathians, France and possibly Hungary) during the Mid-Late Pleistocene, while populations within the Italian and Balkan Peninsulas fluctuated only slightly in distribution range, with larger lowland populations during glacial times and with refugial mountain populations during interglacials, as in the present time. The phylogeographical structure revealed in our study suggests complex recolonization dynamics of the European continent by V. berus, characterized by latitudinal as well as altitudinal range shifts, driven by both climatic changes and competition with related species.

Maternal age-specific risk of non-chromosomal anomalies.

OBJECTIVES: To determine the excess risk of non-chromosomal congenital anomaly (NCA) among teenage mothers and older mothers. DESIGN AND SETTING: Population-based prevalence study using data from EUROCAT congenital anomaly registers in 23 regions of Europe in 15 countries, covering a total of 1.75 million births from 2000 to 2004. PARTICIPANTS: A total of 38,958 cases of NCA that were live births, fetal deaths with gestational age > or = 20 weeks or terminations of pregnancy following prenatal diagnosis of a congenital anomaly. MAIN OUTCOME MEASURES: Prevalence of NCA according to maternal age, and relative risk (RR) of NCA and 84 standard NCA subgroups compared with mothers aged 25-29. RESULTS: The crude prevalence of all NCA was 26.5 per 1000 births in teenage mothers (<20 years), 23.8 for mothers 20-24 years, 22.5 for mothers 25-29 years, 21.5 for mothers 30-34 years, 21.4 for mothers 35-39 years and 22.6 for mothers 40-44 years. The RR adjusted for country for teenage mothers was 1.11 (95% CI 1.06-1.17); 0.99 (95% CI 0.96-1.02) for mothers 35-39; and 1.01 (95% CI 0.95-1.07) for mothers 40-44. The pattern of maternal age-related risk varied significantly between countries: France, Ireland and Portugal had higher RR for teenage mothers, Germany and Poland had higher RR for older mothers. The maternal age-specific RR varied for different NCAs. Teenage mothers were at a significantly greater risk (P < 0.01) of gastroschisis, maternal infection syndromes, tricuspid atresia, anencephalus, nervous system and digestive system anomalies while older mothers were at a significantly greater risk (P < 0.01) of fetal alcohol syndrome, encephalocele, oesophageal atresia and thanatophoric dwarfism. CONCLUSIONS: Clinical and public health interventions are needed to reduce environmental risk factors for NCA, giving special attention to young mothers among whom some risk factors are more prevalent. Reassurance can be given to older mothers that their age in itself does not confer extra risk for NCA.

Platforms for high-throughput screening of Wnt/Frizzled antagonists.

Signaling cascades initiated by Wnt lipoglycoproteins and their receptors of the Frizzled family regulate many aspects of animal development and physiology. Improper activation of this signaling promotes carcinogenic transformation and metastasis. Development of agents blocking the Wnt-Frizzled signaling is of prime interest for drug discovery. Despite certain progress no such agents are as yet brought to the market or even to clinical trials. One reason for these delays might be the use of suboptimal readout assays. In this article we overview existing and developing assay platforms to screen for Wnt-Frizzled antagonists. Among those, G protein-activating assays built on the emerging GPCR properties of Frizzleds are highlighted.

Three essays on major trends in a slow clockspeed industry : the case of industrial automation

The motivation for this research initiated from the abrupt rise and fall of minicomputers which were initially used both for industrial automation and business applications due to their significantly lower cost than their predecessors, the mainframes. Later industrial automation developed its own vertically integrated hardware and software to address the application needs of uninterrupted operations, real-time control and resilience to harsh environmental conditions. This has led to the creation of an independent industry, namely industrial automation used in PLC, DCS, SCADA and robot control systems. This industry employs today over 200'000 people in a profitable slow clockspeed context in contrast to the two mainstream computing industries of information technology (IT) focused on business applications and telecommunications focused on communications networks and hand-held devices. Already in 1990s it was foreseen that IT and communication would merge into one Information and communication industry (ICT). The fundamental question of the thesis is: Could industrial automation leverage a common technology platform with the newly formed ICT industry? Computer systems dominated by complex instruction set computers (CISC) were challenged during 1990s with higher performance reduced instruction set computers (RISC). RISC started to evolve parallel to the constant advancement of Moore's law. These developments created the high performance and low energy consumption System-on-Chip architecture (SoC). Unlike to the CISC processors RISC processor architecture is a separate industry from the RISC chip manufacturing industry. It also has several hardware independent software platforms consisting of integrated operating system, development environment, user interface and application market which enables customers to have more choices due to hardware independent real time capable software applications. An architecture disruption merged and the smartphone and tablet market were formed with new rules and new key players in the ICT industry. Today there are more RISC computer systems running Linux (or other Unix variants) than any other computer system. The astonishing rise of SoC based technologies and related software platforms in smartphones created in unit terms the largest installed base ever seen in the history of computers and is now being further extended by tablets. An underlying additional element of this transition is the increasing role of open source technologies both in software and hardware. This has driven the microprocessor based personal computer industry with few dominating closed operating system platforms into a steep decline. A significant factor in this process has been the separation of processor architecture and processor chip production and operating systems and application development platforms merger into integrated software platforms with proprietary application markets. Furthermore the pay-by-click marketing has changed the way applications development is compensated: Three essays on major trends in a slow clockspeed industry: The case of industrial automation 2014 freeware, ad based or licensed - all at a lower price and used by a wider customer base than ever before. Moreover, the concept of software maintenance contract is very remote in the app world. However, as a slow clockspeed industry, industrial automation has remained intact during the disruptions based on SoC and related software platforms in the ICT industries. Industrial automation incumbents continue to supply systems based on vertically integrated systems consisting of proprietary software and proprietary mainly microprocessor based hardware. They enjoy admirable profitability levels on a very narrow customer base due to strong technology-enabled customer lock-in and customers' high risk leverage as their production is dependent on fault-free operation of the industrial automation systems. When will this balance of power be disrupted? The thesis suggests how industrial automation could join the mainstream ICT industry and create an information, communication and automation (ICAT) industry. Lately the Internet of Things (loT) and weightless networks, a new standard leveraging frequency channels earlier occupied by TV broadcasting, have gradually started to change the rigid world of Machine to Machine (M2M) interaction. It is foreseeable that enough momentum will be created that the industrial automation market will in due course face an architecture disruption empowered by these new trends. This thesis examines the current state of industrial automation subject to the competition between the incumbents firstly through a research on cost competitiveness efforts in captive outsourcing of engineering, research and development and secondly researching process re- engineering in the case of complex system global software support. Thirdly we investigate the industry actors', namely customers, incumbents and newcomers, views on the future direction of industrial automation and conclude with our assessments of the possible routes industrial automation could advance taking into account the looming rise of the Internet of Things (loT) and weightless networks. Industrial automation is an industry dominated by a handful of global players each of them focusing on maintaining their own proprietary solutions. The rise of de facto standards like IBM PC, Unix and Linux and SoC leveraged by IBM, Compaq, Dell, HP, ARM, Apple, Google, Samsung and others have created new markets of personal computers, smartphone and tablets and will eventually also impact industrial automation through game changing commoditization and related control point and business model changes. This trend will inevitably continue, but the transition to a commoditized industrial automation will not happen in the near future.

Prevalence and determinants of obesity in children in public schools of Sintra, Portugal

OBJECTIVE: To assess the prevalence of and the factors related to overweight and obesity in a sample of children from the region of Sintra, Portugal. METHODS AND PROCEDURES: Cross-sectional study, stratified for freguesia with random selection of schools. Height, weight, triceps skinfold, upper arm and waist circumferences were measured, and overweight/obesity defined according to international criteria. Breast-feeding, number of daily meals and parents' height and weight data were also collected. RESULTS: One thousand two hundred and twenty-five children aged 6-10 years were assessed. Overall prevalence of overweight and obesity was 35.6% (23% overweight and 12.6% obesity). Overweight or obese children had higher triceps skinfold, upper arm circumference, arm muscle area, and waist circumference than their normal weight counterparts (P < 0.001). On multivariate analysis, relatively to a child without obese progenitors, a child with one obese progenitor had an obesity risk multiplied by 2.78 (95% confidence interval (CI): 1.76-4.38), while a child with two obese progenitors had a risk multiplied by 6.47 (95% CI: 5.59-16.19). Conversely, being picky was significantly related with a smaller risk of obesity: for boys, odds ratio (OR) = 0.15 (95% CI: 0.04-0.63); for girls, OR = 0.19 (95% CI: 0.06-0.64). Finally, no relationships were found between obesity, birth weight, birth height or breast-feeding. DISCUSSION: Prevalence of overweight and obesity are elevated among children of the Sintra region in Portugal compared to most other regions of Europe. The relationship with the parents' nutritional state stresses the need to target families for preventing obesity.

Aproximació del vigent Pla General Comptable a la NIC 1: presentació dels estats financers

L'objectiu principal del treball consisteix en analitzar quines són les modificacions de la Norma Internacional de Comptabilitat 1: Presentació dels estats financers, i veure com afecta als estats financers de les empreses que cotitzen a borsa i que presenten els seus comptes anuals consolidats. A la vegada, el treball inclou dos estudis empírics. El primer consisteix en analitzar si les empreses de l'Ibex 35 compleixen els requisits de la NIC 1 modificada. I el segon estudi consisteix en fer una anàlisi economica-­‐ financera d'aquestes empreses.

Alps, genes, and chromosomes: their role in the formation of species in the Sorex araneus group (Mammalia, Insectivora), as inferred from two hybrid zones.

During the Pleistocene glaciations, the Alps were an efficient barrier to gene flow between isolated populations, often leading to allopatric speciation. Afterwards, the Alps strongly influenced the post-glacial recolonization of Europe and represent a major suture zone between differentiated populations. Two hybrid zones in the Swiss and French Alps between genetically and chromosomally well-differentiated species-the Valais shrew, Sorex antinorii, and the common shrew, S. araneus-were studied karyotypically and by analyzing the distribution of seven microsatellite loci. In the center of the Haslital hybrid zone the two species coexist over a distance of 900 m. Hybrid karyotypes, among them the most complex known in Sorex, are rare. F-statistics based on microsatellite data revealed a strong heterozygote deficit only in the center of the zone, due to the sympatric distribution of the two species with little hybridization between them. Structuring within the species (both F(IS) and F(ST)) was low. An hierarchical analysis showed a high level of interspecific differentiation. Results were compared with those previously reported in another hybrid zone located at Les Houches in the French Alps. Genetic structuring within and between species was comparable in both hybrid zones, although chromosomal incompatibilities are more important in Haslital, where a linkage block of the race-specific chromosomes should additionally impede gene flow. Evidence for a more restricted gene flow in Haslital comes from the genetically intermediate hybrid karyotypes, whereas in Les Houches, hybrid karyotypes are genetically identical to individuals of the pure karyotypic races. Genic and chromosomal introgression was observed in Les Houches, but not in Haslital. The possible influence of a river, separating the two species at Les Houches, on gene flow is discussed.

Market Index Biases and Minimum Risk Indices

Markets, in the real world, are not efficient zero-sum games where hypotheses of the CAPM are fulfilled. Then, it is easy to conclude the market portfolio is not located on Markowitz"s efficient frontier, and passive investments (and indexing) are not optimal but biased. In this paper, we define and analyze biases suffered by passive investors: the sample, construction, efficiency and active biases and tracking error are presented. We propose Minimum Risk Indices (MRI) as an alternative to deal with to market index biases, and to provide investors with portfolios closer to the efficient frontier, that is, more optimal investment possibilities. MRI (using a Parametric Value-at-Risk Minimization approach) are calculated for three stock markets achieving interesting results. Our indices are less risky and more profitable than current Market Indices in the Argentinean and Spanish markets, facing that way the Efficient Market Hypothesis. Two innovations must be outlined: an error dimension has been included in the backtesting and the Sharpe"s Ratio has been used to select the"best" MRI