The dating of shallow faults in the Earth's crust

Direct dating of ductile shear zones and calculation of uplift/exhumation rates can be done using various radiometric dating techniques. But radiometric dating of shallow crustal faulting, which occurs in the crust's brittle regime, has remained difficult(1-4) because the low temperatures typical of shallow crusted faults prevent the complete syntectonic mineral recrystallization that occurs in deeper faults. Both old (detrital) and newly grown (authigenic) fine-grained phyllosilicates are thus preserved in shallow fault zones and therefore their radiometric ages reflect a mixture of both mineral populations. Also, the loss of Ar-39 during neutron irradiation in dating of clay minerals can produce erroneously old ages. Here we present a method of characterizing the clay populations in fault gouge, using X-ray modelling, combined with sample encapsulation, and show how it can be used to date near-surface fault activity reliably. We examine fault gouge from the Lewis thrust of the southern Canadian Rockies, which we determine to be similar to 52 Myr old. This result requires the western North America stress regime to have changed from contraction to extension in only a few million years during the Eocene. We also estimate the uplift/exhumation age and sedimentary source of these rocks to be similar to 172 Myr.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62567/1/412172a0.pd

Longitudinal Linkages Between Father and Mother Autonomy Support and Adolescent Problem Behaviors: Between-Family Differences and Within-Family

Despite existing evidence on negative associations between parental autonomy support and children’s internalizing and externalizing problem behavior, it is difficult to draw conclusions on the effect that parents’ autonomy support has on children’s problem behavior. This study contributed to the existing literature by unraveling the temporal ordering of parental autonomy support and adolescent problem behavior. In addition, this study examined whether these linkages differed by parent’s sex, child sex, and reporter of autonomy support. Data of 497 adolescents (mean age at T1 = 13.03 years, percentage male = 56.9) and their parents from six annual waves of the Dutch study Research on Adolescent Development And Relationships (RADAR) were used. The results showed that stable differences between families explained most linkages between autonomy support and problem behavior. Adolescents with fewer problem behaviors have fathers (both child- and parent-reported) and mothers (only child-reported) who are more autonomy supportive. The results did not differ between boys and girls. The findings suggest that prior studies may have overstated the existence of a causal effect of parental autonomy support on adolescent problem behavior

Evaluation of hydrogeologic properties of the Barbados accretionary prism: a synthesis of Leg 156 results

In situ and laboratory studies of permeability, conducted by Ocean Drilling Program scientists from Leg 156, provide constraints on parameters controlling the hydrogeologic system in the Barbados accretionary prism. Results from these studies indicate that core-scale and formation-scale permeability values differ by at least several orders of magnitude and are dependent on pore-fluid pressure and effective stress conditions. Direct measurement from packer experiments and indirect evidence from consolidation tests suggest that pore-fluid pressures are commonly above hydrostatic values and approach lithostatic values within the décollement zone. Permeability and fluid pressure conditions in the Barbados accretionary prism reflect the complexity of the hydrogeologic system of such an active tectonic environment

Comparative analysis of the lambda-interferons IL-28A and IL-29 regarding their transcriptome and their antiviral properties against hepatitis C virus.

Specific differences in signaling and antiviral properties between the different Lambda-interferons, a novel group of interferons composed of IL-28A, IL-28B and IL-29, are currently unknown. This is the first study comparatively investigating the transcriptome and the antiviral properties of the Lambda-interferons IL-28A and IL-29. Expression studies were performed by microarray analysis, quantitative PCR (qPCR), reporter gene assays and immunoluminometric assays. Signaling was analyzed by Western blot. HCV replication was measured in Huh-7 cells expressing subgenomic HCV replicon. All hepatic cell lines investigated as well as primary hepatocytes expressed both IFN-λ receptor subunits IL-10R2 and IFN-λR1. Both, IL-28A and IL-29 activated STAT1 signaling. As revealed by microarray analysis, similar genes were induced by both cytokines in Huh-7 cells (IL-28A: 117 genes; IL-29: 111 genes), many of them playing a role in antiviral immunity. However, only IL-28A was able to significantly down-regulate gene expression (n = 272 down-regulated genes). Both cytokines significantly decreased HCV replication in Huh-7 cells. In comparison to liver biopsies of patients with non-viral liver disease, liver biopsies of patients with HCV showed significantly increased mRNA expression of IL-28A and IL-29. Moreover, IL-28A serum protein levels were elevated in HCV patients. In a murine model of viral hepatitis, IL-28 expression was significantly increased. IL-28A and IL-29 are up-regulated in HCV patients and are similarly effective in inducing antiviral genes and inhibiting HCV replication. In contrast to IL-29, IL-28A is a potent gene repressor. Both IFN-λs may have therapeutic potential in the treatment of chronic HCV

High discontinuation rate of azathioprine in autoimmune hepatitis, independent of time of treatment initiation

Contains fulltext : 225262.pdf (Publisher’s version ) (Open Access)BACKGROUND: Guidelines regarding treatment for autoimmune hepatitis (AIH) favour two strategies for azathioprine (AZA) introduction: concurrent with steroids at induction or delayed by 2-4 weeks. The safety and efficacy of both strategies have been unexplored. METHODS: We established a cohort of 900 AIH patients from 12 centres in 7 European countries. There were 631 patients who used AZA as part of the therapeutic regimen. We distinguished two groups: patients with early AZA (<2 weeks) or delayed AZA initiation (≥2 weeks). Primary outcome was discontinuation of AZA in the first year of treatment. Cox regression and propensity score matching was performed to determine difference in outcomes between groups. RESULTS: Patients with early AZA initiation had significantly lower transaminases and bilirubin at baseline. Discontinuation rates of AZA did not differ between early and delayed starters (16.6% vs 14.2%), which did not reach statistical significance (hazard ratio 0.97, 95% confidence interval 0.61-1.55, P = .90). Stratification according to baseline disease activity or propensity score matching did not alter the results. Main reason for AZA discontinuation was intolerance to treatment (14.0% vs 13.2%, P = .78) with nausea and vomiting as main side effects. AIH remission rates were comparable among groups. CONCLUSION: The discontinuation rate of AZA in AIH treatment is ~15% in the first year of treatment. Early or delayed AZA initiation does not differ in remission and discontinuation rates in AIH induction therapy. Our data suggest that either strategy may be used as part of AIH treatment

Predniso(lo)ne Dosage and Chance of Remission in Patients With Autoimmune Hepatitis

Background & Aims Patients with autoimmune hepatitis (AIH) commonly receive induction therapy with predniso(lo)ne followed by maintenance therapy with azathioprine. European Association for Study of the Liver clinical practice guidelines advise a predniso(lo)ne dose range of 0.50–1 mg/kg/day, which leaves room for practice variation. We performed a multicenter study to determine the efficacy of different dose ranges of predniso(lo)ne induction therapy in a large European cohort of patients with AIH. Methods We performed a retrospective cohort study using a comparative effectiveness design. We collected data from 451 adults with AIH who began treatment from 1978 through 2017 at 9 centers in 5 European countries. We assigned patients to a high-dose group (initial predniso(lo)ne dose ≥0.50 mg/kg/day; n=281) or a low-dose group (<0.50 mg/kg/day; n=170). Logistic regression was performed to determine difference in outcomes between the groups. The primary outcome was normal serum levels of transaminases at 6 months after initiation of therapy. Results There was no significant difference in rates of normalization of transaminases between the high-dose predniso(lo)ne group and the low-dose group (70.5% vs 64.7%; P =.20). After multivariable logistic regression with correction for confounders, there was no difference in the likelihood of normalization of transaminases between the groups (odds ratio, 1.21; 95% CI, 0.78 – 1.87; P =.38). Patients given an initial high dose of predniso(lo)ne received more predniso(lo)ne over time than patients started on a lower dose (median doses over 6 months: 3780 mg vs 2573 mg) ( P <.01). Conclusions In a retrospective study of patients with AIH in Europe, we found that the dose of predniso(lo)ne to induce remission in patients with AIH is less relevant than assumed. An initial predniso(lo)ne dose below 0.50 mg/kg/day substantially decreases unnecessary exposure to predniso(lo)ne in patients with AIH

The relation between plasma tyrosine concentration and fatigue in primary biliary cirrhosis and primary sclerosing cholangitis

BACKGROUND: In primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) fatigue is a major clinical problem. Abnormal amino acid (AA) patterns have been implicated in the development of fatigue in several non-hepatological conditions but for PBC and PSC no data are available. This study aimed to identify abnormalities in AA patterns and to define their relation with fatigue. METHODS: Plasma concentrations of tyrosine, tryptophan, phenylalanine, valine, leucine and isoleucine were determined in plasma of patients with PBC (n = 45), PSC (n = 27), chronic hepatitis C (n = 22) and healthy controls (n = 73). Fatigue and quality of life were quantified using the Fisk fatigue severity scale, a visual analogue scale and the SF-36. RESULTS: Valine, isoleucine, leucine were significantly decreased in PBC and PSC. Tyrosine and phenylalanine were increased (p < 0.0002) and tryptophan decreased (p < 0.0001) in PBC. In PBC, but not in PSC, a significant inverse relation between tyrosine concentrations and fatigue and quality of life was found. Patients without fatigue and with good quality of life had increased tyrosine concentrations compared to fatigued patients. Multivariate analysis indicated that this relation was independent from disease activity or severity or presence of cirrhosis. CONCLUSION: In patients with PBC and PSC, marked abnormalities in plasma AA patterns occur. Normal tyrosine concentrations, compared to increased concentrations, may be associated with fatigue and diminished quality of life

The NuRD chromatin–remodeling complex regulates signaling and repair of DNA damage

NuRD is recruited to DNA double-strand breaks, where it promotes RNF8/RNF168 histone ubiquitylation and accumulation of DNA repair factors (see also related paper by Larsen et al. in this issue)