Multi-episodic remagnetization related to deformation in the Pyrenean Internal Sierras

The Internal Sierras (IS) in the southern margin of the Western and Central Axial Zone (Southern Pyrenees) are affected by a syn-orogenic remagnetization that provides information to reconstruct deformation geometries at the time of acquisition of magnetization. Furthermore, the IS structure changes strike along its structural trend, from ∼N120 to 130°E in the western and eastern margins to ∼N070–090°E in the central part. Palaeomagnetic techniques have been used to (i) accurately define the timing of remagnetization with regard to deformation and (ii) determine if the along-strike trend variation in the IS was induced by deformation and thrust emplacement during the Pyrenean compression or, on the contrary, was the result of a primary orientation controlled by structures inherited from pre-orogenic times. From 23 new palaeomagnetic sites, collected in Upper Cretaceous marls and marly limestones, two meaningful and stable palaeomagnetic components were resolved, principally carried by magnetite: (1) a lower-temperature component (B) that unblocks between 200 °C and 325–400 °C and (2) a higher-temperature component (C) that has been successfully isolated by means of combined thermal (up to 400 °C) and AF demagnetization (generally up to 50–100 mT). The B component is a late remagnetization that post-dates folding and emplacement of basement thrust sheets in the IS (mainly the Gavarnie thrust). It supports small but statistically significant clockwise rotations in the western part of the IS (from +18 to +26°). These rotations can be attributed to the westwards shortening decrease in the thrust system below the Gavarnie unit that results from its along-strike structural change, with a higher number of basement thrusts to the east. The C component has been interpreted as an early remagnetization, based on the results of conglomerate and fold tests. This component predates basement thrusting and is diachronous across the study area: reverse and normal polarities dominate in the eastern and western margins of the IS, respectively. New and previous palaeomagnetic data point out that curvature in the IS is probably a primary feature and the along-strike change in their trend could be interpreted as the result of basement geometrical features inherited from Variscan, Late Variscan or Mesozoic times. A complex, multi-episodic remagnetization probably related to burial and deformation processes occurred during Eocene times

Adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab and abatacept for the treatment of rheumatoid arthritis not previously treated with disease-modifying antirheumatic drugs and after the failure of conventional disease-modifying antirheumatic drugs only: systematic review and economic evaluation.

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increasing disability, reduced quality of life and substantial costs (as a result of both intervention acquisition and hospitalisation). The objective was to assess the clinical effectiveness and cost-effectiveness of seven biologic disease-modifying antirheumatic drugs (bDMARDs) compared with each other and conventional disease-modifying antirheumatic drugs (cDMARDs). The decision problem was divided into those patients who were cDMARD naive and those who were cDMARD experienced; whether a patient had severe or moderate to severe disease; and whether or not an individual could tolerate methotrexate (MTX). DATA SOURCES: The following databases were searched: MEDLINE from 1948 to July 2013; EMBASE from 1980 to July 2013; Cochrane Database of Systematic Reviews from 1996 to May 2013; Cochrane Central Register of Controlled Trials from 1898 to May 2013; Health Technology Assessment Database from 1995 to May 2013; Database of Abstracts of Reviews of Effects from 1995 to May 2013; Cumulative Index to Nursing and Allied Health Literature from 1982 to April 2013; and TOXLINE from 1840 to July 2013. Studies were eligible for inclusion if they evaluated the impact of a bDMARD used within licensed indications on an outcome of interest compared against an appropriate comparator in one of the stated population subgroups within a randomised controlled trial (RCT). Outcomes of interest included American College of Rheumatology (ACR) scores and European League Against Rheumatism (EULAR) response. Interrogation of Early Rheumatoid Arthritis Study (ERAS) data was undertaken to assess the Health Assessment Questionnaire (HAQ) progression while on cDMARDs. METHODS: Network meta-analyses (NMAs) were undertaken for patients who were cDMARD naive and for those who were cDMARD experienced. These were undertaken separately for EULAR and ACR data. Sensitivity analyses were undertaken to explore the impact of including RCTs with a small proportion of bDMARD experienced patients and where MTX exposure was deemed insufficient. A mathematical model was constructed to simulate the experiences of hypothetical patients. The model was based on EULAR response as this is commonly used in clinical practice in England. Observational databases, published literature and NMA results were used to populate the model. The outcome measure was cost per quality-adjusted life-year (QALY) gained. RESULTS: Sixty RCTs met the review inclusion criteria for clinical effectiveness, 38 of these trials provided ACR and/or EULAR response data for the NMA. Fourteen additional trials contributed data to sensitivity analyses. There was uncertainty in the relative effectiveness of the interventions. It was not clear whether or not formal ranking of interventions would result in clinically meaningful differences. Results from the analysis of ERAS data indicated that historical assumptions regarding HAQ progression had been pessimistic. The typical incremental cost per QALY of bDMARDs compared with cDMARDs alone for those with severe RA is > £40,000. This increases for those who cannot tolerate MTX (£50,000) and is > £60,000 per QALY when bDMARDs were used prior to cDMARDs. Values for individuals with moderate to severe RA were higher than those with severe RA. Results produced using EULAR and ACR data were similar. The key parameter that affected the results is the assumed HAQ progression while on cDMARDs. When historic assumptions were used typical incremental cost per QALY values fell to £38,000 for those with severe disease who could tolerate MTX. CONCLUSIONS: bDMARDs appear to have cost per QALY values greater than the thresholds stated by the National Institute for Health and Care Excellence for interventions to be cost-effective. Future research priorities include: the evaluation of the long-term HAQ trajectory while on cDMARDs; the relationship between HAQ direct medical costs; and whether or not bDMARDs could be stopped once a patient has achieved a stated target (e.g. remission). STUDY REGISTRATION: This study is registered as PROSPERO CRD42012003386. FUNDING: The National Institute for Health Research Health Technology Assessment programme

Geochronological constraints on mesoproterozoic and neoproterozoic(?) high-grade metasedimentary rocks of north-central Idaho, U.S.A.

We analyzed detrital zircons in seven samples of metasedimentary rock from north-central Idaho, U.S.A., to test the previous assignment of these rocks to the Mesoproterozoic Belt–Purcell Supergroup. Correlating these rocks with known sedimentary units through field observations is difficult if not impossible due to the high metamorphic grade (amphibolite facies) and intensity of deformation. Zircon analysis by laser-ablation inductively coupled plasma mass spectrometry (LA-ICPMS) reveals that five of the seven samples contain multiple zircon populations between 1700 and 1400 Ma and a scatter of Paleoproterozoic and Archean ages, similar to results reported from the Belt Supergroup to the north and east. These results indicate that the likely protoliths of most high-grade metamorphic rocks northwest of the Idaho batholith were upper strata of the Belt Supergroup. In contrast, a quartzite at Bertha Hill north of Pierce lacks grains younger than 1600 Ma and thus is distinctly unlike the Ravalli Group of the Belt Supergroup, with which it was previously correlated. Possible correlatives that contain similarly old populations of zircons and feldspar-poor quartzite include the Neihart Formation (lowermost Belt Supergroup in Montana), Neoproterozoic quartzite (Syringa metamorphic sequence), and Cambrian quartzite. A sample from the North Fork of the Clearwater River yielded a large number of zircons with concordant Neoproterozoic ages, all of which had low Th/U ratios that suggest either a Neoproterozoic metamorphic event or the transport and deposition of zircons that were metamorphosed in the Neoproterozoic. SHRIMP (sensitive high-resolution ion microprobe) dating of a granite (now augen gneiss) that intruded sedimentary rocks west of Pierce, Idaho, yields an age of 1379 ± 12 Ma based on seven of fourteen analyses; this provides a lower age limit for sediment deposition of some rocks mapped as metamorphosed Belt Supergroup, and which had detrital zircon populations in the 1700 to 1400 Ma range. Additional analyses of three zircon rims yield an age range of 87–82 Ma, which is similar to the youngest ages from the North Fork sample. We interpret these ages to reflect the time of zircon overgrowth synchronous with the emplacement of the Cretaceous Idaho Batholith. None of the metasedimentary rocks dated can be older than Mesoproterozoic, and, with the exception of the Bertha Hill quartzite, none can be older than the Belt–Purcell Supergroup

I Am A Monument

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