Genotype 3 is associated with rapid histological progression in chronic HCV infection

While several risk factors for the histological progression of chronic hepatitis C have been identified, the contribution of HCV genotypes to liver fibrosis evolution remains controversial. The aim of the present study was to assess independent predictors for fibrosis progression. Methods: We identified 1540 patients from the Swiss Hepatitis C Cohort database with at least one liver biopsy prior to antiviral treatment. Factors associated with fibrosis stage, steatosis and histological activity were assessed in univariate and multivariate regression models. Fibrosis progression rate per year was calculated in a subgroup of 1263 patients, in whom risk factors were assessed by cumulative incidence curves, logistic and linear regression models. Results: Independent risk factors for rapid fibrosis progression included male sex (OR = 1.66, 95% CI 1.25-2.21, P <0.001), age at infection (OR = 1.08, 95% CI 1.06-1.10, P <0.001), histological activity (OR = 2.14, 95% CI 1.61-2.85, P <0.001) and genotype 3 (OR = 1.97, 95% CI 1.43-2.72, P <0.001). Genotype 2 was associated with slow progression (OR = 0.51, 95% CI 0.30-0.89, P = 0.02), but this observation may be due to the decreased prevalence of genotype 2 over the last decades, leading to an overrepresentation of subjects with genotype 2 with a slow progression rate. Conclusion: This study shows a significant association of genotype 3 with accelerated fibrosis. While assessing risk factors for fibrosis progression, the changing epidemiology of HCV genotypes over time needs to be taken into account.

Long-Term Safety of Canakinumab in Patients with Gouty Arthritis.

Background/Purpose: Gouty arthritis (GA) is a chronic inflammatory disease. Targeting the inflammatory pathway through IL-1_ inhibition with canakinumab (CAN) may provide significant long-term benefits. CAN safety versus triamcinolone acetonide (TA) over initial 24 weeks (blinded study) for patients (pts) with history of frequent attacks (_3 in year before baseline) was reported earlier from core (_-RELIEVED [_-REL] and _-REL-II) and first extension (E1) studies1. Herein we present full 18-month long-term CAN safety data, including open-label second extension (E2) studies. Methods: GA pts completing _-REL E1 and _-REL-II E1 studies1 were enrolled in these 1-year, open-label, E2 studies. All pts entering E2, whether randomized to CAN or TA, received CAN 150 mg sc on demand upon new attack. Data are presented only for pts randomized to CAN, and are reported cumulatively, i.e. including corresponding data from previously reported core and E1 studies. Long-term safety outcomes and safety upon re-treatment are presented as incidence rate per 100 patient-years (pyr) of study participation for AEs and SAEs. Deaths are reported for all pts (randomized to CAN or TA). Selected predefined notable laboratory abnormalities are shown (neutrophils, platelets, liver and renal function tests). Long-term attack rate per year is also provided. Results: In total, 69/115 (60%) and 72/112 (64.3%) of the pts randomized to CAN in the two core studies entered the two E2 studies, of which 68 and 64 pts, respectively completed the E2 studies. The 2 study populations had differing baseline comorbidity and geographic origin. Lab data (not time adjusted) for neutropenia appears worse after retreatment in _-REL E2, and deterioration of creatinine clearance appears worse after retreatment (Table 1). The time-adjusted incidence rates for AEs were 302.4/100 pyr and 360/100 pyr, and for SAEs were 27.9/100 pyr and 13.9/100 pyr in _-REL E2 and _-REL-II E2 respectively (Table 1). The time-adjusted incidence rates of any AEs, infection AEs, any SAEs, and selected SAEs before and after re-treatment are presented in Table 1. Incidence rates for AEs and SAEs declined after re-treatment, with the exception of SAEs in _-REL-II E2, which increased from 2.9/100 pyr to 10.9/100 pyr (no infection SAEs after retreatment in _-REL-II E2, and other SAEs fit no special pattern). In the total safety population (N_454, core and all extensions), there were 4 deaths, 2 in the core studies previously reported1 and 2 during the _-REL E2 study (one patient in the CAN group died from pneumonia; one patient in the TA group who never received CAN died of pneumococcal sepsis). None of the deaths was suspected by investigators to be study drug related. The mean rates of new attacks per year on CAN were 1.21 and 1.18 in _-REL E2 and in _-REL-II E2. Conclusion: The clinical safety profile of CAN upon re-treatment was maintained long-term with no new infection concerns

Fracture rates of IPS Empress all-ceramic crowns: a systematic review.

Purpose: The aim of this study was to evaluate the clinical fracture rate of crowns fabricated with the pressable, leucite-reinforced ceramic IPS Empress, and relate the results to the type of tooth restored. Materials and Methods: The database SCOPUS was searched for clinical studies involving full-coverage crowns made of IPS Empress. To assess the fracture rate of the crowns in relation to the type of restored tooth and study, Poisson regression analysis was used. Results: Seven clinical studies were identified involving 1,487 adhesively luted crowns (mean observation time: 4.5 +/- 1.7 years) and 81 crowns cemented with zinc-phosphate cement (mean observation time: 1.6 +/- 0.8 years). Fifty-seven of the adhesively luted crowns fractured (3.8%). The majority of fractures (62%) occurred between the third and sixth year after placement. There was no significant influence regarding the test center on fracture rate, but the restored tooth type played a significant role. The hazard rate (per year) for crowns was estimated to be 5 in every 1,000 crowns for incisors, 7 in every 1,000 crowns for premolars, 12 in every 1,000 crowns for canines, and 16 in every 1,000 crowns for molars. One molar crown in the zinc-phosphate group fractured after 1.2 years. Conclusion: Adhesively luted IPS Empress crowns showed a low fracture rate for incisors and premolars and a somewhat higher rate for molars and canines. The sample size of the conventionally luted crowns was too small and the observation period too short to draw meaningful conclusions. Int J Prosthodont 2010;23:129-133.

Development of Values after Compulsory School: Work comes first, then family

During school-to-work transition, adolescents develop values and prioritize what is im-portant in their life. Values are concepts or beliefs about desirable states or behaviors that guide the selection or evaluation of behavior and events, and are ordered by their relative importance (Schwartz & Bilsky, 1987). Stressing the important role of values, career re-search has intensively studied the effect of values on educational decisions and early career development (e.g. Eccles, 2005; Hirschi, 2010; Rimann, Udris, & Weiss, 2000). Few re-searchers, however, have investigated so far how values develop in the early career phase and how value trajectories are influenced by individual characteristics. Values can be oriented towards specific life domains, such as work or family. Work values include intrinsic and extrinsic aspects of work (e.g., self-development, cooperation with others, income) (George & Jones, 1997). Family values include the importance of partner-ship, the creation of an own family and having children (Mayer, Kuramschew, & Trommsdroff, 2009). Research indicates that work values change considerably during early career development (Johnson, 2001; Lindsay & Knox, 1984). Individual differences in work values and value trajectories are found e.g., in relation to gender (Duffy & Sedlacek, 2007), parental background (Loughlin & Barling, 2001), personality (Lowry et al., 2012), educa-tion (Battle, 2003), and the anticipated timing of school-to-work transition (Porfeli, 2007). In contrast to work values, research on family value trajectories is rare and knowledge about the development during the school-to-work transition and early career development is lack-ing. This paper aims at filling this research gap. Focusing on family values and intrinsic work values and we expect a) family and work val-ues to change between ages 16 and 25, and b) that initial levels of family and work values as well as value change to be predicted by gender, reading literacy, ambition, and expected du-ration of education. Method. Using data from 2620 young adults (59.5% females), who participated in the Swiss longitudinal study TREE, latent growth modeling was employed to estimate the initial level and growth rate per year for work and family values. Analyses are based on TREE-waves 1 (year 2001, first year after compulsory school) to 8 (year 2010). Variables in the models included family values and intrinsic work values, gender, reading literacy, ambition and ex-pected duration of education. Language region was included as control variable. Results. Family values did not change significantly over the first four years after leaving compulsory school (mean slope = -.03, p =.36). They increased, however, significantly five years after compulsory school (mean slope = .13, p >.001). Intercept (.23, p < .001), first slope (.02, p < .001), and second slope (.01, p < .001) showed significant variance. Initial levels were higher for men and those with higher ambitions. Increases were found to be steeper for males as well as for participants with lower educational duration expectations and reading skills. Intrinsic work values increased over the first four years (mean slope =.03, p <.05) and showed a tendency to decrease in the years five to ten (mean slope = -.01, p < .10). Intercept (.21, p < .001), first slope (.01, p < .001), and second slope (.01, p < .001) showed signifi-cant variance, meaning that there are individual differences in initial levels and growth rates. Initial levels were higher for females, and those with higher ambitions, expecting longer educational pathways, and having lower reading skills. Growth rates were lower for the first phase and steeper for the second phase for males compared to females. Discussion. In general, results showed different patterns of work and family value trajecto-ries, and different individual factors related to initial levels and development after compul-sory school. Developments seem to fit to major life and career roles: in the first years after compulsory school young adults may be engaged to become established in one's job; later on, raising a family becomes more important. That we found significant gender differences in work and family trajectories may reflect attempts to overcome traditional roles, as over-all, women increase in work values and men increase in family values, resulting in an over-all trend to converge.

Diatom assemblages, HBIs and TEXL86 in sediment core NBP99-03_10

The West Antarctic ice sheet is particularly sensitive to global warming and its evolution and impact on global climate over the next few decades remains difficult to predict. In this context, investigating past sea ice conditions around Antarctica is of primary importance. Here, we document changes in sea ice presence, upper water column temperatures (0-200 m) and primary productivity over the last 9000 yr BP (before present) in the western Antarctic Peninsula (WAP) margin from a sedimentary core collected in the Palmer Deep Basin. Employing a multi-proxy approach, based on the combination of two biomarkers proxies (highly branched isoprenoid (HBI) alkenes for sea ice and TEXL86 for temperature) and micropaleontological data (diatom assemblages), we derived new Holocene records of sea ice conditions and upper water column temperatures. The early Holocene (9000-7000 yr BP) was characterized by a cooling phase with a short sea ice season. During the mid-Holocene (~7000-3800 yr BP), local climate evolved towards slightly colder conditions and a prominent extension of the sea ice season occurred, promoting a favorable environment for intensive diatom growth. The late Holocene (the last ~2100 yr) was characterized by warmer temperatures and increased sea ice presence, accompanied by reduced local primary productivity, likely in response to a shorter growing season compared to the early or mid-Holocene. The gradual increase in annual sea ice duration over the last 7000 yr might have been influenced by decreasing mean annual and spring insolation, despite increasing summer insolation. We postulate that, in addition to precessional changes in insolation, seasonal variability, via changes in the strength of the circumpolar Westerlies and upwelling activity, was further amplified by the increasing frequency/amplitude of the El Nino-Southern Oscillation (ENSO). However, between 3800 and 2100 yr BP, the lack of correlation between ENSO and climate variability in the WAP suggests that other climatic factors might have been more important in controlling WAP climate at this time.

Pollen record and age determination of a sediment profile from Schmiechener See, Germany

Die untersuchten Schluffe und Kiese sind unter kaltzeitlichen Bedingungen in einem See mit Schwimmpflanzengesellschaften abgelagert worden. Zur Sedimentationszeit gab es in der Umgebung des Sees eine tundrenartige Vegetation, die auch Steppenarten enthielt.

Palynological and geochemical data of sediment core GeoB3910-2 located offshore Northeast Brazil

High resolution palynological and geochemical data of sediment core GeoB 3910-2 (located offshore Northeast Brazil) spanning the period between 19 600 and 14 500 calibrated year bp (19.6-14.5 ka) show a land-cover change in the catchment area of local rivers in two steps related to changes in precipitation associated with Heinrich Event 1 (H1 stadial). At the end of the last glacial maximum, the landscape in semi-arid Northeast Brazil was dominated by a very dry type of caatinga vegetation, mainly composed of grasslands with some herbs and shrubs. After 18 ka, considerably more humid conditions are suggested by changes in the vegetation and by Corg and C/N data indicative of fluvial erosion. The caatinga became wetter and along lakes and rivers, sedges and gallery forest expanded. The most humid period was recorded between 16.5 and 15 ka, when humid gallery (and floodplain) forest and even small patches of mountainous Atlantic rain forest occurred together with dry forest, the latter being considered as a rather lush type of caatinga vegetation. During this humid phase erosion decreased as less lithogenic material and more organic terrestrial material were deposited on the continental slope of northern Brazil. After 15 ka arid conditions returned. During the humid second phase of the H1 stadial, a rich variety of landscapes existed in Northeast Brazil and during the drier periods small pockets of forest could probably survive in favorable spots, which would have increased the resilience of the forest to climate change.

Geochemical composition and ages of sediment core BELQ300 obtained from Lake Belau, north Germany

Geochemical and palynological data from an annually laminated core sequence (Lake Belau, Schleswig-Holstein) are interpreted with respect to vegetation and settlement history on the basis of a chronostratigraphical model and archaeological evidence. Most settlement periods indicated by pollen and archaeological data can be geochemically identified in the sediment sequence using tracer elements such as K, Rb, Zr and the K/Zr ratio. Whilst air-borne pollen carry a more regional signal, the sedimentary flux of these trace elements is determined by the allogenic input from the catchment area of the lake and, therefore, provides information about the local history of settlement and agricultural land use in the lake's vicinity. This is exemplified for the period of the middle Neolithic Funnel Beaker Culture ('Iversen landnam'), where a time offset of 250 years between both signals has been detected. In contrast, both geochemical and pollen signals are highly synchronous during the Early Migration Period and the High Medieval Period. Additionally, the Fe/Ca and/or U/Fe ratio may serve as a sensitive tracer for human impact on the trophic state of the lake. The suggested impact of the Romans and the High Medieval civilization can clearly be seen (and quantified) from elevated lead input into Lake Belau sediments at this time. Effects of secular climatic changes on the sedimentary chemistry have not been detected and, if present, seem to have been obliterated by anthropogenic activity.

Beryllium-10 and aluminium-26 concentration and production rates in glacial deposits from the Quartermain Mountains

Many glacial deposits in the Quartermain Mountains, Antarctica present two apparent contradictions regarding the degradation of unconsolidated deposits. The glacial deposits are up to millions of years old, yet they have maintained their meter-scale morphology despite the fact that bedrock and regolith erosion rates in the Quartermain Mountains have been measured at 0.1-4.0 m/Ma. Additionally, ground ice persists in some Miocene-aged soils in the Quartermain Mountains even though modeled and measured sublimation rates of ice in Antarctic soils suggest that without any recharge mechanisms ground ice should sublimate in the upper few meters of soil on the order of 10**3 to 10**5 years. This paper presents results from using the concentration of cosmogenic nuclides beryllium-10 (10Be) and aluminum-26 (26Al) in bulk sediment samples from depth profiles of three glacial deposits in the Quartermain Mountains. The measured nuclide concentrations are lower than expected for the known ages of the deposits, erosion alone does not always explain these concentrations, and deflation of the tills by the sublimation of ice coupled with erosion of the overlying till can explain some of the nuclide concentration profiles. The degradation rates that best match the data range 0.7-12 m/Ma for sublimation of ice with initial debris concentrations ranging 12-45% and erosion of the overlying till at rates of 0.4-1.2 m/Ma. Overturning of the tills by cryoturbation, vertical mixing, or soil creep is not indicated by the cosmogenic nuclide profiles, and degradation appears to be limited to within a few centimeters of the surface. Erosion of these tills without vertical mixing may partially explain how some glacial deposits in the Quartermain Mountains maintain their morphology and contain ground ice close to the surface for millions of years.