Soft-bed experiments beneath Engabreen, Norway: regelation infiltration, basal slip and bed deformation

To avoid some of the limitations of studying soft-bed processes through boreholes, a prism of simulated till (1.8 m × 1.6 m × 0.45 m) with extensive instrumentation was constructed in a trough blasted in the rock bed of Engabreen, a temperate glacier in Norway. Tunnels there provide access to the bed beneath 213 m of ice. Pore-water pressure was regulated in the prism by pumping water to it. During experiments lasting 7–12 days, the glacier regelated downward into the prism to depths of 50– 80 mm, accreting ice-infiltrated till at rates predicted by theory. During periods of sustained high pore water pressure (70–100% of overburden), ice commonly slipped over the prism, due to a water layer at the prism surface. Deformation of the prism was activated when this layer thinned to a sub-millimeter thickness. Shear strain in the till was pervasive and decreased with depth. A model of slip by ploughing of ice-infiltrated till across the prism surface accounts for the slip that occurred when effective pressure was sufficiently low or high. Slip at low effective pressures resulted from water-layer thickening that increased non-linearly with decreasing effective pressure. If sufficiently widespread, such slip over soft glacier beds, which involves no viscous deformation resistance, may instigate abrupt increases in glacier velocity

Persistent Hepatitis B Viral Replication in a FVB/N Mouse Model: Impact of Host and Viral Factors

The mechanism underlying the chronicity of hepatitis B virus (HBV) infection has long been an interesting question. However, this mechanism remains unclear largely due to the lack of an animal model that can support persistent HBV replication and allow for the investigation of the relevant immune responses. In this study, we used hydrodynamic injection to introduce HBV replicon DNA into the livers of three different mouse strains: BALB/c, C57BL/6, and FVB/N. Interestingly, we found that an HBV clone persistently replicated in the livers of FVB/N mice for up to 50 weeks but was rapidly cleared from the livers of BALB/c and C57BL/6 mice. Flow cytometric analysis and quantitative reverse transcription PCR analysis of the mouse livers indicated that after DNA injection, FVB/N mice had few intrahepatic activated cytotoxic T lymphocytes (CTLs) and produced low levels of alanine aminotransferase, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and the CXCL9 and CXCL10 chemokines. These findings were in sharp contrast with those observed in BALB/c and C57BL/6 mice, reflecting a strong correlation between the degree of liver inflammation and viral clearance. Mutational analysis further demonstrated that a change of Asn-214 to Ser-214 in the HBV surface antigen rendered the persistent HBV clone clearable in FVB/N mice, which was accompanied by increased levels of activated CTL and upregulated expression of IFN-γ, CXCL9, and CXCL10 in the livers. These results indicate that the heterogeneity of the host factors and viral sequences may influence the immune responses against HBV. An inadequate activation of immune or inflammatory responses can lead to persistent HBV replication in vivo

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Beyond the Economic Gaze: Childbearing During and After Recessions in the Nordic Countries

none9siDuring the 2010s, fertility rates fell across the Nordic region. The onset of these declines seems linked to the Great Recession of 2008-2009, but their continuation cannot easily be linked to subsequent economic change. The 1990s, too, brought episodes of economic crises to the Nordic region that were followed by different degrees of fertility decline. In this study, we provide an empirical overview of parity-, age- and education-specific fertility developments in the five Nordic countries in the wake of the economic recessions in 2008 and the early 1990s, respectively. We demonstrate a high degree of heterogeneity in fertility developments across countries after 1990, whereas after 2008, the trends are much more similar across the five countries. Likewise, the educational differences in birth hazards that characterized the developments after 1990 were much smaller in the initial years after 2008-2009. This reversal from heterogeneity to homogeneity in the fertility response to recessions calls for an expansion of theories on the cyclicality of fertility in relation to uncertainty and economic and social change. In our discussion, we consider the role of a set of factors that also incorporates the state, crisis management, and perceptions of economic and welfare uncertainty.mixedComolli C; Neyer G; Andersson G; Dommermuth L; Fallesen P; Jalovaara M; Jonsson AK; Kolk M; Lappegard TComolli C; Neyer G; Andersson G; Dommermuth L; Fallesen P; Jalovaara M; Jonsson AK; Kolk M; Lappegard

Soft-bed experiments beneath Engabreen, Norway: regelation infiltration, basal slip and bed deformation

To avoid some of the limitations of studying soft-bed processes through boreholes, a prism of simulated till (1.8 m × 1.6 m × 0.45 m) with extensive instrumentation was constructed in a trough blasted in the rock bed of Engabreen, a temperate glacier in Norway. Tunnels there provide access to the bed beneath 213 m of ice. Pore-water pressure was regulated in the prism by pumping water to it. During experiments lasting 7–12 days, the glacier regelated downward into the prism to depths of 50– 80 mm, accreting ice-infiltrated till at rates predicted by theory. During periods of sustained high pore water pressure (70–100% of overburden), ice commonly slipped over the prism, due to a water layer at the prism surface. Deformation of the prism was activated when this layer thinned to a sub-millimeter thickness. Shear strain in the till was pervasive and decreased with depth. A model of slip by ploughing of ice-infiltrated till across the prism surface accounts for the slip that occurred when effective pressure was sufficiently low or high. Slip at low effective pressures resulted from water-layer thickening that increased non-linearly with decreasing effective pressure. If sufficiently widespread, such slip over soft glacier beds, which involves no viscous deformation resistance, may instigate abrupt increases in glacier velocity.This article is from Journal of Glaciology 53 (2007): 323, doi:10.3189/002214307783258431. Posted with permission.</p

Non-Invasive whole-body detection of complement activation using radionuclide imaging in a mouse model of myocardial ischaemia-reperfusion injury

Abstract Complement activation is a recognised mediator of myocardial ischaemia-reperfusion-injury (IRI) and cardiomyocytes are a known source of complement proteins including the central component C3, whose activation products can mediate tissue inflammation, cell death and profibrotic signalling. We investigated the potential to detect and quantify the stable covalently bound product C3d by external body imaging, as a marker of complement activation in heart muscle in a murine model of myocardial IRI. We used single-photon-emission-computed-tomography (SPECT) in conjunction with 99mTechnecium-labelled recombinant complement receptor 2 (99mTc-rCR2), which specifically detects C3d at the site of complement activation. Compared to control imaging with an inactive CR2 mutant (99mTc-K41E CR2) or an irrelevant protein (99mTc-PSMA) or using 99mTc-rCR2 in C3-deficient mice, the use of 99mTc-rCR2 in complement-intact mice gave specific uptake in the reperfused myocardium. The heart to skeletal muscle ratio of 99mTc-rCR2 was significantly higher than in the three control groups. Histological analysis confirmed specific uptake of 99mTc-rCR2. Following therapeutic inhibition of complement C3 activation, we found reduced myocardial uptake of 99mTc-rCR2. We conclude, therefore that 99mTc-rCR2 imaging can be used for non-invasive detection of activated complement and in future could be exploited to quantify the severity of myocardial damage due to complement activation