The Palaeozoic metamorphic evolution of the Alpine External Massifs

The pre-Mesozoic metamorphic pattern of the External Massifs, composed of subunits of different metamorphic histories, resulted from the telescoping of Variscan, Ordovician and older metamorphic and structural textures and formations. During an early period, the future External Massifs were part of a peri-Gondwanian microplate evolving as an active margin. Precambrian to lower Palaeozoic igneous and sedimentary protoliths were reworked during an Ordovician subduction cycle (eclogites, granulites) preceding Ordovician anatexis and intrusion of Ordovician granitoids. Little is known about the time period when the microcontinent containing the future External Massifs followed a migration path leading to collision with Laurussia. Corresponding rock-series have not been identified. This might be because they have been eroded or transformed by migmatisation or because they remain hidden in the monocyclic areas. Besides the transformations which originated during the Ordovician subduction cycle, strong metamorphic transformations resulted from Variscan collision when many areas underwent amphibolite facies transformations and migmatisation. The different subunits composing the External Massifs and their corresponding P-T evolution are the expression of different levels in a nappe pile, which may have formed before Visean erosion and cooling. The presence of durbachitic magmatic rocks may be the expression of a large scale Early Variscan upwelling line which formed after Variscan lithospheric subduction. Late Variscan wrench fault tectonics and crustal thinning accompanied by high thermal gradients triggered several pulses of granite intrusions.

Occurrence of sectoral choroidal occlusive vasculopathy and retinal arteriolar embolization after superselective ophthalmic artery chemotherapy for advanced intraocular retinoblastoma.

BACKGROUND: : Superselective ophthalmic artery chemotherapy (SOAC) has recently been proposed as an alternative to intravenous chemoreduction for advanced intraocular retinoblastoma. Preliminary results appear promising in terms of tumor control and eye conservation, but little is known regarding ocular toxicity and visual prognosis. In this study, we report on the vascular adverse effects observed in our initial cohort of 13 patients. METHODS: : The charts of 13 consecutive patients with retinoblastoma who received a total of 30 injections (up to 3 injections of a single agent per patient at 3-week interval) of melphalan (0.35 mg/kg) in the ophthalmic artery between November 2008 and June 2010 were retrospectively reviewed. RetCam fundus photography and fluorescein angiography were performed at presentation and before each injection. Vision was assessed at the latest visit. RESULTS: : Enucleation and external beam radiotherapy could be avoided in all cases but one, with a mean follow-up of 7 months. Sectoral choroidal occlusive vasculopathy leading to chorioretinal atrophy was observed temporally in 2 eyes (15%) 3 weeks to 6 weeks after the beginning of SOAC and retinal arteriolar emboli in 1 eye 2 weeks after injection. There was no stroke or other clinically significant systemic side effects except a perioperative transient spasm of the internal carotid artery in one patient. Vision ranged between 20/1600 and 20/32 depending on the status of the macula. CONCLUSION: : Superselective ophthalmic artery chemotherapy was effective in all patients with no stroke or other systemic vascular complications. Unlike intravenous chemoreduction, SOAC is associated with potentially sight-threatening adverse effects, such as severe chorioretinal atrophy secondary to subacute choroidal occlusive vasculopathy or central retinal artery embolism, not to mention the risk of ophthalmic artery obstruction, which was not observed in this series. Further analysis of the risks and benefits of SOAC will define its role within the therapeutic arsenal. Meanwhile, we suggest that SOAC should be given in one eye only and restricted to advanced cases of retinoblastoma, as an alternative to enucleation and/or external beam radiotherapy.

Phytochrome interacting factors 4 and 5 redundantly limit seedling de-etiolation in continuous far-red light.

Phytochromes are red/far-red photosensors that regulate numerous developmental programs in plants. Among them, phytochrome A (phyA) is essential to enable seedling de-etiolation under continuous far-red (FR) light, a condition that mimics the environment under a dense canopy. The ecological relevance of this response is demonstrated by the high mortality rate of phyA mutant plants that germinate in deep vegetational shade. phyA signaling involves direct interaction of the photoreceptor with phytochrome-interacting factors PIF1 and PIF3, members of the bHLH transcription factor family. Here we investigated the involvement of PIF4 and PIF5 in phyA signaling, and found that they redundantly control de-etiolation in FR light. The pif4 pif5 double mutant is hypersensitive to low fluence rates of FR light. This phenotype is dependent on FR light perception by phyA, but does not rely on alterations in the phyA level. Our microarray analysis shows that PIF4 and PIF5 are part of an inhibitory mechanism that represses the expression of some light-responsive genes in the dark, and that they are also needed for full expression of several growth-related genes in the light. Unlike PIF1 and PIF3, PIF4 and PIF5 are not degraded in response to FR light, indicating that they are light-regulated by a different mechanism. Our genetic analysis suggests that this is achieved through sequestration of these PIFs by the closely related bHLH transcription factor HFR1 (long hypocotyl in FR light).

Shedding light on proteolytic cleavage of CD44: the responsible sheddase and functional significance of shedding.

CD44 is the major cell-surface receptor for hyaluronan, which is implicated in cell-cell and cell-matrix adhesion, cell migration, and signaling. Studies have shown that CD44-dependent migration requires CD44 to be shed from the cell surface and that matrix metalloproteinase-mediated cleavage may provide an underlying mechanism. However, the full spectrum of proteases that may participate in CD44 shedding has yet to be defined. In this issue, Anderegg et al. demonstrate that ADAM10, but not ADAM17 or MMP14, mediates constitutive shedding of CD44 in human melanoma cells and that knockdown of ADAM10 blocks the antiproliferative activity of the soluble proteolytic cleavage product of CD44.

Atrial natriuretic peptide administered as intravenous infusion or bolus injection to patients with liver cirrhosis and ascites.

The effect of a synthetic atrial natriuretic peptide (h-ANP, 25 amino acids, Wy-47.663) on blood pressure, renal electrolyte excretion, plasma catecholamines, and plasma renin activity was studied in nine patients with cirrhosis of the liver and ascites. The peptide was infused intravenously at 24-h intervals for 2 h in groups of four patients each in two different doses (0.015 and 0.075 micrograms/kg/min or 0.06 and 0.3 micrograms/kg/min). A control experiment with the vehicle was performed in all patients. In three patients h-ANP (1 and 2 micrograms/kg i.v.) was administered as an intravenous bolus injection. Consistent falls in blood pressure were observed during h-ANP infusion only with the two higher doses. The two lower infused doses induced a consistent natriuresis; this renal response was abolished when the two larger doses were used. When given as a bolus, h-ANP had a natriuretic effect comparable to that of the two lower doses of infused h-ANP. Plasma catecholamines and plasma renin activity increased during infusion of the two higher doses of h-ANP. It thus appears that in patients with cirrhosis and ascites, the natriuretic effect of infused h-ANP decreases rather than increases when the doses are raised. Bolus administration of h-ANP may be less prone to trigger counterbalancing responses and side-effects.

Subconjunctival Injection of XG-102, a JNK Inhibitor Peptide, in Patients with Intraocular Inflammation: A Safety and Tolerability Study.

Abstract Purpose: We aimed to investigate the safety, tolerability, and systemic diffusion of a single escalating dose of XG-102 (a 31-D-amino-acid peptide inhibiting JNK pathway activation), administered subconjunctivally in the treatment of post-surgery or post-trauma intraocular inflammation. Methods: This is a dose-escalating, tolerance Phase Ib study. Twenty patients with post-surgery or post-traumatic intraocular inflammation were assigned to 1 of the 4 dose escalating (45, 90, 450, or 900 μg XG-102) groups of 5 patients each. Patients were evaluated at 24, 48 h, 8, and 28 days following the administration of XG-102, including laboratory tests, standard eye examinations, vital signs, and occurrence of adverse events. A single plasma quantification of XG-102 was performed 30 min after administration, according to previous pharmacokinetics studies performed on volunteers. Results: A total of 17 non-serious adverse events, considered unrelated to the study treatment, were reported for 10 patients. The adverse event incidence was not related to the drug dose. All patients experienced a decrease in intraocular inflammation as of 24 h post-administration and this decrease was sustained up to 28 days thereafter. No patient required local injection or systemic administration of corticoids following the administration of XG-102. XG-102 was undetectable in the first 3 dose groups. In the fourth-dose group (900 μg) the XG-102 plasma levels were above the limit of detection for 3 patients and above the limit of quantification for 1 patient. Conclusions: In this first clinical trial using XG-102, administered as a single subconjunctival injection as adjunct therapy, in patients with recent post-surgery or post-trauma intraocular inflammation is safe and well tolerated. Further studies are required to evaluate its efficacy.

Biases of the ordinary least squares and instrumental variables estimators of the intergenerational earnings elasticity : revisited in the light of panel data

The OLS estimator of the intergenerational earnings correlation is biased towards zero, while the instrumental variables estimator is biased upwards. The first of these results arises because of measurement error, while the latter rests on the presumption that the education of the parent family is an invalid instrument. We propose a panel data framework for quantifying the asymptotic biases of these estimators, as well as a mis-specification test for the IV estimator. [Author]

The Variscan evolution in the External massifs of the Alps and place in their Variscan framework

In the general discussion on the Variscan evolution of central Europe the pre-Mesozoic basement of the Alps is, in many cases, only included with hesitation. Relatively well-preserved from Alpine metamorphism, the Alpine External massifs can serve as an excellent example of evolution of the Variscan basement, including the earliest Gondwana-derived microcontinents with Cadomian relics. Testifying to the evolution at the Gondwana margin, at least since the Cambrian, such pieces took part in the birth of the Rheic Ocean. After the separation of Avalonia, the remaining Gondwana border was continuously transformed through crustal extension with contemporaneous separation of continental blocks composing future Pangea, but the opening of Palaeotethys had only a reduced significance since the Devonian. The Variscan evolution in the External domain is characterised by an early HP-evolution with subsequent granulitic decompression melts. During Visean crustal shortening, the areas of future formation of migmatites and intrusion of monzodioritic magmas in a general strike-slip regime, were probably in a lower plate situation, whereas the so called monometamorphic areas may have been in an upper plate position of the nappe pile. During the Latest Carboniferous, the emplacement of the youngest granites was associated with the strike-slip faulting and crustal extension at lower crustal levels, whereas, at the surface, detrital sediments accumulated in intramontaneous transtensional basins on a strongly eroded surface. To cite this article: J.R von Raumer et al., C. R. Geoscience 341 (2009). (C) 2008 Academie des sciences. Published by Elsevier Masson SAS. All rights reserved.

Maturation of the lymphoid system. III. Induction of selective unresponsiveness by injection of a haptenated carbohydrate into neonatal mice.

Neonatal treatment of A/J mice with DNP-Ficoll reduced or eliminated indirect anti-DNP PFC normally produced in response to adult challenge with DNP-keyhole limpet hemocyanin. The remaining direct anti-DNP PFC response was of low avidity. Spleen cells from neonatal A/J mice inhibited the in vitro but not the in vivo response of adult spleen cells to DNP-Ficoll.

Leukocyte-endothelial cell interaction is necessary for photodynamic therapy induced vascular permeabilization.

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) affects vascular barrier function and thus increases vessel permeability. This phenomenon may be exploited to facilitate targeted drug delivery and may lead to a new clinical application of photodynamic therapy. Here, we investigate the role of leukocyte recruitment for PDT-induced vascular permeabilization. STUDY DESIGN/MATERIAL AND METHODS: Fluorescein isothiocyanate dextran (FITC-D, 2,000 kDa) was injected intravenously 120 minutes after focal PDT on striated muscle in nude mice bearing dorsal skinfold chambers (Visudyne® 800 µg/kg, fluence rate 300 mW/cm2 , light dose of 200 J/cm2). Leukocyte interaction with endothelial cells was inhibited by antibodies functionally blocking adhesion molecules ("MABS-PDT" group, n = 5); control animals had PDT but no antibody injection (group "PDT", n = 7). By intravital microscopy, we monitored leukocyte rolling and sticking in real-time before, 90 and 180 minutes after PDT. The extravasation of FITC-D from striated muscle vessels into the interstitial space was determined in vivo during 45 minutes to assess treatment-induced alterations of vascular permeability. RESULTS: PDT significantly increased the recruitment of leukocytes and enhanced the leakage of FITC-D. Neutralization of adhesion molecules before PDT suppressed the rolling of leukocytes along the venular endothelium and significantly reduced the extravasation of FITC-D as compared to control animals (156 ± 27 vs. 11 ± 2 (mean ± SEM, number of WBC/30 seconds mm vessel circumference; P < 0.05) at 90 minutes after PDT and 194 ± 21 vs. 14 ± 4 at 180 minutes after PDT). In contrast, leukocyte sticking was not downregulated by the antibody treatment. CONCLUSION: Leukocyte recruitment plays an essential role in the permeability-enhancing effect of PDT.

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Pollution of air, water and soil by industrial chemicals presents a potential health risk to humans. Such chemicals can enter the human body by three routes, namely by inhalation, dermal absorption, and ingestion and in special cases by injection (needle sticks, bites, cuts, etc.). In the workplace, pulmonary and dermal absorption are the main routes of entry, but poor personal hygiene and work habits can result in ingestion that contributes to the dose. Air monitoring provides reliable information on inhalation exposure, and patches can be used to estimate dermal exposure. Local adverse effects, such as skin and eye irritation, or nose and lung irritation, are closely related to the external exposure. Systemic adverse effects, on the other hand, are related to the absorbed amount (dose), or to the level of the pollutant or its metabolite in the target organ. Human biological monitoring is becoming a powerful tool for scientists and policy makers to assess and manage the risk of exposure to chemicals both in the general population and at the workpalce. This chapter will focus on the occupational environment keeping in mind that biological monitoring in humans is a very actual issue in public health politics, in environmental medicine, and in science in general.

Localized amyloid light-chain amyloidosis and extramedullary plasmacytoma of the mitral valve.

An unusual case of localized amyloid light-chain (AL) amyloidosis and extramedullary plasmacytoma of the mitral valve is described. The worsening of a mitral regurgitation led to investigations and surgery. The valve presented marked distortion and thickening by type AL amyloid associated with a monotypic CD138+ immunoglobulin lambda plasma cell proliferation. Systemic staging showed a normal bone marrow and no evidence of amyloid deposition in other localizations. The patient's outcome after mitral valve replacement was excellent. To our knowledge, this is the first description of a localized AL amyloidosis as well as of a primary extramedullary plasmacytoma of the mitral valve.

CT-guided sacroiliac joint injection: Easy or difficult? : 53

Purpose: Fluoroscopy-guided sacroiliac joint (SIJ) injections are technically difficult to perform because of the complex anatomy with helicoidal conformation of the joint. Our study describes the procedure of CT-guided SIJ injection, its feasibility and its rate of success. Methods and materials: Retrospective study included 46 consecutive patients. The procedure was performed by 3 MSK radiologists and consisted in a puncture with a posterior approach in the inferior articular part of SIJ, then in an injection of iodinated contrast agent (1ml) with CT control of SIJ space opacification and finally in an injection of slowacting corticosteroid. The SIJ approach was noticed as correct if there was an inferior articular puncture and if the needle was in the articular space, and as impossible if there was ankylosis or osteophytosis. The study was divided in two successive periods: period 1 (4 first months) and period 2 (12 last months). Results: SIJ opacification was successful in 57% (26/46). We observed a learning curve: opacification was succeeded in 66% (23/35) and there was incorrect approach in 9% (3/35) during period 2 versus respectively 27% (3/11) and 45% (5/11) during period 1. Causes of failure were incorrect approach in 40% (6/20 too low, 2/20 too high), impossible approach in 30% (6/20) and unexplained in 30% (6/20). Mean duration of procedure was about 28 minutes. No complication occurred. Conclusion: CT guided SIJ injection is safe and successful in 66% after a training period. The success depends on SIJ correct approach and also on anatomical lesions.