High-throughput and sensitive quantitation of plasma catecholamines by ultraperformance liquid chromatography-tandem mass spectrometry using a solid phase microwell extraction plate.

Plasma catecholamines provide a reliable biomarker of sympathetic activity. The low circulating concentrations of catecholamines and analytical interferences require tedious sample preparation and long chromatographic runs to ensure their accurate quantification by HPLC with electrochemical detection. Published or commercially available methods relying on solid phase extraction technology lack sensitivity or require derivatization of catecholamine by hazardous reagents prior to tandem mass spectrometry (MS) analysis. Here, we manufactured a novel 96-well microplate device specifically designed to extract plasma catecholamines prior to their quantification by a new and highly sensitive ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. Processing time, which included sample purification on activated aluminum oxide and elution, is less than 1 h per 96-well microplate. The UPLC-MS/MS analysis run time is 2.0 min per sample. This UPLC-MS/MS method does not require a derivatization step, reduces the turnaround time by 10-fold compared to conventional methods used for routine application, and allows catecholamine quantification in reduced plasma sample volumes (50-250 μL, e.g., from children and mice).

Post-mortem β-hydroxybutyrate determination in synovial fluid.

β-hydroxybutyrate concentrations were determined in blood and synovial fluid in a series of medico-legal cases including hypothermia fatalities, individuals found dead in a cold environment and non-hypothermia cases with various, non-traumatic causes of death. Hypothermia was considered to be the cause of death according to circumstantial elements indicating exposure to cold, autopsy findings, biochemical investigation results and exclusion of other causes of death. The intention of this study was to characterize β-hydroxybutyrate distribution in synovial fluid and assess its usefulness for the postmortem diagnosis of antemortem abnormalities in blood β-hydroxybutyrate levels. Unenhanced CT scans, autopsies, histology, neuropathology, toxicology, and biochemistry were systematically performed. Within the limited number of subjects included in the study, the results indicate that abnormalities in antemortem β-hydroxybutyrate blood levels, as may be observed in hypothermia fatalities, are reflected in postmortem synovial fluid values. These preliminary findings notwithstanding, synovial fluid analysis to determine β-hydroxybutyrate is unlikely to be generally applied due to the more invasive collection technique it requires and could be limited to special cases in which biological fluids systematically collected upon autopsy are unavailable.

Effectiveness of Electrochemical Chloride Extraction for the Iowa Avenue Pedestrian Bridge, TR-499, 2005

The main objective of this study is to determine the effectiveness of the Electrochemical Chloride Extraction (ECE) technique on a bridge deck with very high concentrations of chloride. This ECE technique was used during the summer of 2003 to reverse the effects of corrosion, which had occurred in the reinforcing steel embedded in the pedestrian bridge deck over Highway 6, along Iowa Avenue, in Iowa City, Iowa, USA. First, the half cell potential was measured to determine the existing corrosion level in the field. The half-cell potential values were in the indecisive range of corrosion (between -200 mV and -350 mV). The ECE technique was then applied to remove the chloride from the bridge deck. The chloride content in the deck was significantly reduced from 25 lb/cy to 4.96 lb/cy in 8 weeks. Concrete cores obtained from the deck were measured for their compressive strengths and there was no reduction in strength due to the ECE technique. Laboratory tests were also performed to demonstrate the effectiveness of the ECE process. In order to simulate the corrosion in the bridge deck, two reinforced slabs and 12 reinforced beams were prepared. First, the half-cell potentials were measured from the test specimens and they all ranged below -200 mV. Upon introduction of 3% salt solution, the potential reached up to -500 mV. This potential was maintained while a salt solution was being added for six months. The ECE technique was then applied to the test specimens in order to remove the chloride from them. Half-cell potential was measured to determine if the ECE technique can effectively reduce the level of corrosion.

Cerebrospinal fluid soluble amyloid-β protein precursor as a potential novel biomarkers of Alzheimer's disease.

In this report, we confirm our previous findings of increased concentrations of soluble amyloid-β protein precursor (sAβPP) in cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) in a large cohort of patients (n = 314), not overlapping with those of our previous study, and we extend our observations by including a control group of participants with normal cognition. In addition, we investigate the effects of age, the APOEε4 genotype, and the blood-CSF barrier function on the concentrations of sAβPPα and sAβPPβ. The study participants were categorized according to clinical-neuropsychological criteria, supported by CSF neurochemical dementia diagnostics (NDD) analyses. sAβPPα concentrations in the AD group (132.0 ± 44.8) were significantly higher than in the control group (105.3 ± 37.3, p < 0.0005) but did not differ from the MCI-AD group (138.5 ± 39.5, p = 0.91). The MCI-AD group differed significantly from the MCI-O (97.3 ± 34.3, p < 0.05) group. There was no difference between the control and the MCI-O groups (p = 0.94). Similarly, sAβPPβ concentrations in the AD group (160.2 ± 54.3) were significantly higher than in the control group (129.9 ± 44.6, p < 0.005) but did not differ from the MCI-AD group (184.0 ± 56.4, p = 0.20). The MCI-AD group differed significantly from the MCI-O (127.8 ± 46.2, p < 0.05) group. There was no difference between the control and the MCI-O groups (p > 0.99). We observed highly significant correlation of the two sAβPP forms. Age and the CSF-serum albumin ratio were significant albeit weak predictors of the sAβPPα and sAβPPβ concentrations, while carrying the APOEε4 allele did not influenced the levels of the sAβPP forms. Taken together, the results strongly suggest that CSF sAβPP concentrations may be considered as an extension of already available NDD tools.

Percolation and three-dimensional structure of supercritical water

It is well established that at ambient and supercooled conditions water can be described as a percolating network of H bonds. This work is aimed at identifying, by neutron diffraction experiments combined with computer simulations, a percolation line in supercritical water, where the extension of the H-bond network is in question. It is found that in real supercritical water liquidlike states are observed at or above the percolation threshold, while below this threshold gaslike water forms small, sheetlike configurations. Inspection of the three-dimensional arrangement of water molecules suggests that crossing of this percolation line is accompa- nied by a change of symmetry in the first neighboring shell of molecules from trigonal below the line to tetrahedral above.

Improved diagnosis of periprosthetic joint infection by multiplex PCR of sonication fluid from removed implants.

The microbiological diagnosis of periprosthetic joint infection (PJI) is crucial for successful antimicrobial treatment. Cultures have limited sensitivity, especially in patients receiving antibiotics. We evaluated the value of multiplex PCR for detection of microbial DNA in sonication fluid from removed orthopedic prostheses. Cases of PJI in which the prosthesis (or part of it) was removed were prospectively included. The removed implant was sonicated, and the resulting sonication fluid was cultured and subjected to multiplex PCR. Of 37 PJI cases (17 hip prostheses, 14 knee prostheses, 4 shoulder prostheses, 1 elbow prosthesis, and 1 ankle prosthesis), pathogens were identified in periprosthetic tissue in 24 (65%) cases, in sonication fluid in 23 (62%) cases, and by multiplex PCR in 29 (78%) cases. The pathogen was detected in 5 cases in sonication fluid only (Propionibacterium acnes in all cases; none of these patients had previously received antibiotics) and in 11 cases by multiplex PCR only (all of these patients had previously received antibiotics). After exclusion of 8 cases caused by P. acnes or Corynebacterium species, which cannot be detected due to the absence of specific primers in the PCR kit, sonication cultures were positive in 17 cases and multiplex PCR sonication cultures were positive in 29 cases (59% versus 100%, respectively; P < 0.01). Among 19 cases (51%) receiving antibiotics, multiplex PCR was positive in all 19 (100%), whereas sonication cultures grew the organism in 8 (42%) (P < 0.01). Multiplex PCR of sonication fluid is a promising test for diagnosis of PJI, particularly in patients who previously received antibiotics. With modified primer sets, multiplex PCR has the potential for further improvement of the diagnosis of PJI.

Fluid dynamical prediction of changed v1-flow at energies available at the CERN Large Hadron Collider

Substantial collective flow is observed in collisions between lead nuclei at Large Hadron Collider (LHC) as evidenced by the azimuthal correlations in the transverse momentum distributions of the produced particles. Our calculations indicate that the global v1-flow, which at RHIC peaked at negative rapidities (named third flow component or antiflow), now at LHC is going to turn toward forward rapidities (to the same side and direction as the projectile residue). Potentially this can provide a sensitive barometer to estimate the pressure and transport properties of the quark-gluon plasma. Our calculations also take into account the initial state center-of-mass rapidity fluctuations, and demonstrate that these are crucial for v1 simulations. In order to better study the transverse momentum flow dependence we suggest a new"symmetrized" vS1(pt) function, and we also propose a new method to disentangle global v1 flow from the contribution generated by the random fluctuations in the initial state. This will enhance the possibilities of studying the collective Global v1 flow both at the STAR Beam Energy Scan program and at LHC.

Fluid geochemistry of the Acqui Terme-Visone geothermal area (Piemonte, Italy)

The main geothermal reservoir of Acqui Terme-Visone hosts Na-Cl waters, which are in chemical equilibrium at 120-130 degrees C with typical hydrothermal minerals including quartz, albite, K-feldspar, illite, chlorite (or smectite), anhydrite, calcite and an unspecified Ca-Al-silicate. In the Acqui Terme-Visone area, these geothermal waters ascend along zones of high vertical permeability and discharge at the surface almost undiluted or mixed with cold, shallow waters. To the SW of Acqui Terme, other ascending geothermal waters, either undiluted or mixed with low-salinity waters, enter relatively shallow secondary reservoirs, where they reequilibrate at 65-70 degrees C. Both chemical and isotopic data indicate that bacterial SO4 reduction affects all these waters, especially those discharged by the secondary reservoirs. Therefore, geothermal waters must get in contact with oil, acquiring the relatively oxidized organic substances needed by SO4-reducing bacteria. This oil-water interaction process deserves further investigations, for potential economic implications. (C) 2000 Elsevier Science Ltd. All rights reserved.

Pore-scale modeling of two-phase flow instabilities in porous media

Les problèmes d'écoulements multiphasiques en média poreux sont d'un grand intérêt pour de nombreuses applications scientifiques et techniques ; comme la séquestration de C02, l'extraction de pétrole et la dépollution des aquifères. La complexité intrinsèque des systèmes multiphasiques et l'hétérogénéité des formations géologiques sur des échelles multiples représentent un challenge majeur pour comprendre et modéliser les déplacements immiscibles dans les milieux poreux. Les descriptions à l'échelle supérieure basées sur la généralisation de l'équation de Darcy sont largement utilisées, mais ces méthodes sont sujettes à limitations pour les écoulements présentant de l'hystérèse. Les avancées récentes en terme de performances computationnelles et le développement de méthodes précises pour caractériser l'espace interstitiel ainsi que la distribution des phases ont favorisé l'utilisation de modèles qui permettent une résolution fine à l'échelle du pore. Ces modèles offrent un aperçu des caractéristiques de l'écoulement qui ne peuvent pas être facilement observées en laboratoire et peuvent être utilisé pour expliquer la différence entre les processus physiques et les modèles à l'échelle macroscopique existants. L'objet premier de la thèse se porte sur la simulation numérique directe : les équations de Navier-Stokes sont résolues dans l'espace interstitiel et la méthode du volume de fluide (VOF) est employée pour suivre l'évolution de l'interface. Dans VOF, la distribution des phases est décrite par une fonction fluide pour l'ensemble du domaine et des conditions aux bords particulières permettent la prise en compte des propriétés de mouillage du milieu poreux. Dans la première partie de la thèse, nous simulons le drainage dans une cellule Hele-Shaw 2D avec des obstacles cylindriques. Nous montrons que l'approche proposée est applicable même pour des ratios de densité et de viscosité très importants et permet de modéliser la transition entre déplacement stable et digitation visqueuse. Nous intéressons ensuite à l'interprétation de la pression capillaire à l'échelle macroscopique. Nous montrons que les techniques basées sur la moyenne spatiale de la pression présentent plusieurs limitations et sont imprécises en présence d'effets visqueux et de piégeage. Au contraire, une définition basée sur l'énergie permet de séparer les contributions capillaires des effets visqueux. La seconde partie de la thèse est consacrée à l'investigation des effets d'inertie associés aux reconfigurations irréversibles du ménisque causé par l'interface des instabilités. Comme prototype pour ces phénomènes, nous étudions d'abord la dynamique d'un ménisque dans un pore angulaire. Nous montrons que, dans un réseau de pores cubiques, les sauts et reconfigurations sont si fréquents que les effets d'inertie mènent à différentes configurations des fluides. A cause de la non-linéarité du problème, la distribution des fluides influence le travail des forces de pression, qui, à son tour, provoque une chute de pression dans la loi de Darcy. Cela suggère que ces phénomènes devraient être pris en compte lorsque que l'on décrit l'écoulement multiphasique en média poreux à l'échelle macroscopique. La dernière partie de la thèse s'attache à démontrer la validité de notre approche par une comparaison avec des expériences en laboratoire : un drainage instable dans un milieu poreux quasi 2D (une cellule Hele-Shaw avec des obstacles cylindriques). Plusieurs simulations sont tournées sous différentes conditions aux bords et en utilisant différents modèles (modèle intégré 2D et modèle 3D) afin de comparer certaines quantités macroscopiques avec les observations au laboratoire correspondantes. Malgré le challenge de modéliser des déplacements instables, où, par définition, de petites perturbations peuvent grandir sans fin, notre approche numérique apporte de résultats satisfaisants pour tous les cas étudiés. - Problems involving multiphase flow in porous media are of great interest in many scientific and engineering applications including Carbon Capture and Storage, oil recovery and groundwater remediation. The intrinsic complexity of multiphase systems and the multi scale heterogeneity of geological formations represent the major challenges to understand and model immiscible displacement in porous media. Upscaled descriptions based on generalization of Darcy's law are widely used, but they are subject to several limitations for flow that exhibit hysteric and history- dependent behaviors. Recent advances in high performance computing and the development of accurate methods to characterize pore space and phase distribution have fostered the use of models that allow sub-pore resolution. These models provide an insight on flow characteristics that cannot be easily achieved by laboratory experiments and can be used to explain the gap between physical processes and existing macro-scale models. We focus on direct numerical simulations: we solve the Navier-Stokes equations for mass and momentum conservation in the pore space and employ the Volume Of Fluid (VOF) method to track the evolution of the interface. In the VOF the distribution of the phases is described by a fluid function (whole-domain formulation) and special boundary conditions account for the wetting properties of the porous medium. In the first part of this thesis we simulate drainage in a 2-D Hele-Shaw cell filled with cylindrical obstacles. We show that the proposed approach can handle very large density and viscosity ratios and it is able to model the transition from stable displacement to viscous fingering. We then focus on the interpretation of the macroscopic capillary pressure showing that pressure average techniques are subject to several limitations and they are not accurate in presence of viscous effects and trapping. On the contrary an energy-based definition allows separating viscous and capillary contributions. In the second part of the thesis we investigate inertia effects associated with abrupt and irreversible reconfigurations of the menisci caused by interface instabilities. As a prototype of these phenomena we first consider the dynamics of a meniscus in an angular pore. We show that in a network of cubic pores, jumps and reconfigurations are so frequent that inertia effects lead to different fluid configurations. Due to the non-linearity of the problem, the distribution of the fluids influences the work done by pressure forces, which is in turn related to the pressure drop in Darcy's law. This suggests that these phenomena should be taken into account when upscaling multiphase flow in porous media. The last part of the thesis is devoted to proving the accuracy of the numerical approach by validation with experiments of unstable primary drainage in a quasi-2D porous medium (i.e., Hele-Shaw cell filled with cylindrical obstacles). We perform simulations under different boundary conditions and using different models (2-D integrated and full 3-D) and we compare several macroscopic quantities with the corresponding experiment. Despite the intrinsic challenges of modeling unstable displacement, where by definition small perturbations can grow without bounds, the numerical method gives satisfactory results for all the cases studied.

Measurement of β-tryptase in postmortem serum, pericardial fluid, urine and vitreous humor in the forensic setting.

In the realm of forensic pathology, β-tryptase measurement for diagnostic purposes is performed in postmortem serum obtained from femoral blood. This may be partially or completely unavailable in some specific cases, such as infant autopsies and severely damaged bodies. The aim of this study was to investigate the usefulness of determining β-tryptase levels for diagnostic purposes in alternative biological samples. Urine, vitreous humor and pericardial fluid were selected and measured in 94 subjects including: fatal anaphylaxis following contrast material administration (6 cases), hypothermia (10 cases), diabetic ketoacidosis (10 cases), gunshot suicide (10 cases), heroin injection-related deaths (18 cases), trauma (10 cases), sudden death with minimal coronary atherosclerosis (10 cases), severe coronary atherosclerosis without myocardial infarction (10 cases) and severe coronary atherosclerosis with myocardial infarction (10 cases). Postmortem serum and pericardial fluid β-tryptase levels higher than the clinical reference value (11.4ng/ml) were systematically identified in fatal anaphylaxis following contrast material administration and 6 cases unrelated to anaphylaxis. β-tryptase concentrations in urine and vitreous humor were lower than the clinical reference value in all cases included in this study. Determination of β-tryptase in pericardial fluid appears to be a possible alternative to postmortem serum in the early postmortem period when femoral blood cannot be collected during autopsy and biochemical investigations are required to objectify increased β-tryptase levels.

Determinants of the essential one-carbon metabolism metabolites, homocysteine, S-adenosylmethionine, S-adenosylhomocysteine and folate, in cerebrospinal fluid.

BACKGROUND: Disturbances in the levels of one-carbon (1C) metabolism metabolites have been associated with a wide variety of neuropsychiatric diseases. Cerebrospinal fluid (CSF) levels of homocysteine (Hcy) and the other 1C metabolites, nor their interrelatedness and putative determinants, have been studied extensively in a healthy population. METHODS: Plasma and CSF samples from 100 individuals free from neuropsychiatric diseases were analyzed (55 male, 45 female; age 50±17 years). In blood, we measured plasma Hcy, serum folate and serum vitamin B12. In CSF, we measured total Hcy, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) and 5-methyltetrahydrofolate (5-methylTHF). Highly selective analytical methods like liquid chromatography combined with either mass spectrometry or fluorescence detection were used. RESULTS: CSF Hcy was inversely correlated with CSF 5-methylTHF and positively with plasma Hcy, independent of serum folate status. CSF SAH correlated with age, lower CSF 5-methylTHF and higher CSF Hcy. CSF 5-methylTHF showed independent negative correlations with age and positive correlations with serum folate. CSF SAM did not correlate with any of the 1C metabolites. CONCLUSIONS: Aging is characterized by a reduction in CSF 5-methylTHF levels and increased CSF levels of the potentially neurotoxic transmethylation inhibitor SAH. CSF 5-methylTHF, which is itself determined in part by systemic folate status, is a powerful independent determinant of CSF levels of Hcy and SAH.

Transrectal specimen extraction after laparoscopic left colectomy: a case-matched study.

Aim  Avoiding 'mini-laparotomy' to extract a colectomy specimen may decrease wound complications and further improve recovery after laparoscopic surgery. The aim of this study was to develop a new technique for transrectal specimen extraction (TRSE) and to compare it with conventional laparoscopy (CL) for left sided colectomy. Method  Eleven patients with benign disease requiring either sigmoid or left colon resection underwent TRSE. The unfired circular stapler was inserted transanally and used as a guide to suture-close the recto-sigmoid junction laparoscopically and as a handle to pull the sutured sigmoid through the opened rectum inside a laparoscopic camera bag. The anvil was inserted into the lumen of the intussuscepted sigmoid and pushed to the level of the anastomosis. The anastomosis was fashioned end-to-end in the first patients and side-to-end in the following patients to improve safety. Intra-operative and postoperative outcomes of patients undergoing TRSE were compared with those of a group of 20 patients undergoing CL, who were matched for type of resection, body mass index and age. Results  The procedure was successful in all but the first patient who was converted to conventional laparoscopic colectomy without any additional morbidity. Two patients in the end-to-end anastomosis group, but none in the side-to-end group, developed peri-anastomotic sepsis. Compared with CL, patients undergoing TRSE did not show any significant differences in operative time, recovery or morbidity. Conclusion  Transrectal specimen extraction after left colectomy using the circular stapler technique is feasible. A side-to-end anastomosis appears safer than an end-to-end anastomosis. Further studies are needed to explore the potential advantages of this procedure over CL.

Detection and characterization of hydraulically active fractures in a carbonate aquifer: Results from self-potential, temperature and fluid conductivity logging along a 260-m-deep borehole in the Combioula hydrothermal system in the southwestern Swiss Alps

A geophysical and geochemical study has been conducted in a fractured carbonate aquifer located at Combioula in the southwestern Swiss Alps with the objective to detect and characterize hydraulically active fractures along a 260-m-deep borehole. Hydrochemical analyses, borehole diameter, temperature and fluid electrical conductivity logging data were integrated in order to relate electrokinetic self-potential signals to groundwater flow inside the fracture network. The results show a generally good, albeit locally variable correlation of variations of the self-potential signals with variations in temperature, fluid electrical conductivity and borehole diameter. Together with the hydrochemical evidence, which was found to be critical for the interpretation of the self-potential data, these measurements not only made it possible to detect the hydraulically active fractures but also to characterize them as zones of fluid gain or fluid loss. The results complement the available information from the corresponding litholog and illustrate the potential of electrokinetic self-potential signals in conjunction with temperature, fluid electrical conductivity and hydrochemical analyses for the characterization of fractured aquifers, and thus may offer a perspective for an effective quantitative characterization of this increasingly important class of aquifers and geothermal reservoirs.

Impact of restrictive intravenous fluid replacement and combined epidural analgesia on perioperative volume balance and renal function within a Fast Track program.

BACKGROUND AND OBJECTIVE: Key factors of Fast Track (FT) programs are fluid restriction and epidural analgesia (EDA). We aimed to challenge the preconception that the combination of fluid restriction and EDA might induce hypotension and renal dysfunction. METHODS: A recent randomized trial (NCT00556790) showed reduced complications after colectomy in FT patients compared with standard care (SC). Patients with an effective EDA were compared with regard to hemodynamics and renal function. RESULTS: 61/76 FT patients and 59/75 patients in the SC group had an effective EDA. Both groups were comparable regarding demographics and surgery-related characteristics. FT patients received significantly less i.v. fluids intraoperatively (1900 mL [range 1100-4100] versus 2900 mL [1600-5900], P < 0.0001) and postoperatively (700 mL [400-1500] versus 2300 mL [1800-3800], P < 0.0001). Intraoperatively, 30 FT compared with 19 SC patients needed colloids or vasopressors, but this was statistically not significant (P = 0.066). Postoperative requirements were low in both groups (3 versus 5 patients; P = 0.487). Pre- and postoperative values for creatinine, hematocrit, sodium, and potassium were similar, and no patient developed renal dysfunction in either group. Only one of 82 patients having an EDA without a bladder catheter had urinary retention. Overall, FT patients had fewer postoperative complications (6 versus 20 patients; P = 0.002) and a shorter median hospital stay (5 [2-30] versus 9 d [6-30]; P< 0.0001) compared with the SC group. CONCLUSIONS: Fluid restriction and EDA in FT programs are not associated with clinically relevant hemodynamic instability or renal dysfunction.

Construction mechanisms and thermal evolution of upper crustal intrusions : the Saint-Jean-du-Doigt bimodal intrusion (Brittany, France)

Understanding the emplacement and growth of intrusive bodies in terms of mechanism, duration, ther¬mal evolution and rates are fundamental aspects of crustal evolution. Recent studies show that many plutons grow in several Ma by in situ accretion of discrete magma pulses, which constitute small-scale magmatic reservoirs. The residence time of magmas, and hence their capacities to interact and differentiate, are con¬trolled by the local thermal environment. The latter is highly dependant on 1) the emplacement depth, 2) the magmas and country rock composition, 3) the country rock thermal conductivity, 4) the rate of magma injection and 5) the geometry of the intrusion. In shallow level plutons, where magmas solidify quickly, evi¬dence for magma mixing and/or differentiation processes is considered by many authors to be inherited from deeper levels. This work shows however that in-situ differentiation and magma interactions occurred within basaltic and felsic sills at shallow depth (0.3 GPa) in the St-Jean-du-Doigt (SJDD) bimodal intrusion, France. This intrusion emplaced ca. 347 Ma ago (IDTIMS U/Pb on zircon) in the Precambrian crust of the Armori- can massif and preserves remarkable sill-like emplacement processes of bimodal mafic-felsic magmas. Field evidence coupled to high precision zircon U-Pb dating document progressive thermal maturation within the incrementally built ioppolith. Early m-thick mafic sills (eastern part) form the roof of the intrusion and are homogeneous and fine-grained with planar contacts with neighboring felsic sills; within a minimal 0.8 Ma time span, the system gets warmer (western part). Sills are emplaced by under-accretion under the old east¬ern part, interact and mingle. A striking feature of this younger, warmer part is in-situ differentiation of the mafic sills in the top 40 cm of the layer, which suggests liquids survival in the shallow crust. Rheological and thermal models were performed in order to determine the parameters required to allow this observed in- situ differentiation-accumulation processes. Strong constraints such as total emplacement durations (ca. 0.8 Ma, TIMS date) and pluton thickness (1.5 Km, gravity model) allow a quantitative estimation of the various parameters required (injection rates, incubation time,...). The results show that in-situ differentiation may be achieved in less than 10 years at such shallow depth, provided that: (1) The differentiating sills are injected beneath consolidated, yet still warm basalt sills, which act as low conductive insulating screens (eastern part formation in the SJDD intrusion). The latter are emplaced in a very short time (800 years) at high injection rate (0.5 m/y) in order to create a "hot zone" in the shallow crust (incubation time). This implies that nearly 1/3 of the pluton (400m) is emplaced by a subsequent and sustained magmatic activity occurring on a short time scale at the very beginning of the system. (2) Once incubation time is achieved, the calculations show that a small hot zone is created at the base of the sill pile, where new injections stay above their solidus T°C and may interact and differentiate. Extraction of differentiated residual liquids might eventually take place and mix with newly injected magma as documented in active syn-emplacement shear-zones within the "warm" part of the pluton. (3) Finally, the model show that in order to maintain a permanent hot zone at shallow level, injection rate must be of 0.03 m/y with injection of 5m thick basaltic sills eveiy 130yr, imply¬ing formation of a 15 km thick pluton. As this thickness is in contradiction with the one calculated for SJDD (1.5 Km) and exceed much the average thickness observed for many shallow level plutons, I infer that there is no permanent hot zone (or magma chambers) at such shallow level. I rather propose formation of small, ephemeral (10-15yr) reservoirs, which represent only small portions of the final size of the pluton. Thermal calculations show that, in the case of SJDD, 5m thick basaltic sills emplaced every 1500 y, allow formation of such ephemeral reservoirs. The latter are formed by several sills, which are in a mushy state and may interact and differentiate during a short time.The mineralogical, chemical and isotopic data presented in this study suggest a signature intermediate be¬tween E-MORB- and arc-like for the SJDD mafic sills and feeder dykes. The mantle source involved produced hydrated magmas and may be astenosphere modified by "arc-type" components, probably related to a sub¬ducting slab. Combined fluid mobile/immobile trace elements and Sr-Nd isotopes suggest that such subduc¬tion components are mainly fluids derived from altered oceanic crust with minor effect from the subducted sediments. Close match between the SJDD compositions and BABB may point to a continental back-arc setting with little crustal contamination. If so, the SjDD intrusion is a major witness of an extensional tectonic regime during the Early-Carboniferous, linked to the subduction of the Rheno-Hercynian Ocean beneath the Variscan terranes. Also of interest is the unusual association of cogenetic (same isotopic compositions) K-feldspar A- type granite and albite-granite. A-type granites may form by magma mixing between the mafic magma and crustal melts. Alternatively, they might derive from the melting of a biotite-bearing quartz-feldspathic crustal protolith triggered by early mafic injections at low crustal levels. Albite-granite may form by plagioclase cu¬mulate remelting issued from A-type magma differentiation.