Combined use of the GGSFT data base and on Board Marine Collected Data to Model the Moho Beneath the Powell Basin, Antarctica

The Powell Basin is a small oceanic basin located at the NE end of the Antarctic Peninsula developed during the Early Miocene and mostly surrounded by the continental crusts of the South Orkney Microcontinent, South Scotia Ridge and Antarctic Peninsula margins. Gravity data from the SCAN 97 cruise obtained with the R/V Hespérides and data from the Global Gravity Grid and Sea Floor Topography (GGSFT) database (Sandwell and Smith, 1997) are used to determine the 3D geometry of the crustal-mantle interface (CMI) by numerical inversion methods. Water layer contribution and sedimentary effects were eliminated from the Free Air anomaly to obtain the total anomaly. Sedimentary effects were obtained from the analysis of existing and new SCAN 97 multichannel seismic profiles (MCS). The regional anomaly was obtained after spectral and filtering processes. The smooth 3D geometry of the crustal mantle interface obtained after inversion of the regional anomaly shows an increase in the thickness of the crust towards the continental margins and a NW-SE oriented axis of symmetry coinciding with the position of an older oceanic spreading axis. This interface shows a moderate uplift towards the western part and depicts two main uplifts to the northern and eastern sectors.

Reticulocyte dynamic and hemoglobin variability in hemodialysis patients treated with Darbepoetin alfa and C.E.R.A.: a randomized controlled trial.

BACKGROUND: In a simulation based on a pharmacokinetic model we demonstrated that increasing the erythropoiesis stimulating agents (ESAs) half-life or shortening their administration interval decreases hemoglobin variability. The benefit of reducing the administration interval was however lessened by the variability induced by more frequent dosage adjustments. The purpose of this study was to analyze the reticulocyte and hemoglobin kinetics and variability under different ESAs and administration intervals in a collective of chronic hemodialysis patients. METHODS: The study was designed as an open-label, randomized, four-period cross-over investigation, including 30 patients under chronic hemodialysis at the regional hospital of Locarno (Switzerland) in February 2010 and lasting 2 years. Four subcutaneous treatment strategies (C.E.R.A. every 4 weeks Q4W and every 2 weeks Q2W, Darbepoetin alfa Q4W and Q2W) were compared with each other. The mean square successive difference of hemoglobin, reticulocyte count and ESAs dose was used to quantify variability. We distinguished a short- and a long-term variability based respectively on the weekly and monthly successive difference. RESULTS: No difference was found in the mean values of biological parameters (hemoglobin, reticulocytes, and ferritin) between the 4 strategies. ESAs type did not affect hemoglobin and reticulocyte variability, but C.E.R.A induced a more sustained reticulocytes response over time and increased the risk of hemoglobin overshooting (OR 2.7, p = 0.01). Shortening the administration interval lessened the amplitude of reticulocyte count fluctuations but resulted in more frequent ESAs dose adjustments and in amplified reticulocyte and hemoglobin variability. Q2W administration interval was however more favorable in terms of ESAs dose, allowing a 38% C.E.R.A. dose reduction, and no increase of Darbepoetin alfa. CONCLUSIONS: The reticulocyte dynamic was a more sensitive marker of time instability of the hemoglobin response under ESAs therapy. The ESAs administration interval had a greater impact on hemoglobin variability than the ESAs type. The more protracted reticulocyte response induced by C.E.R.A. could explain both, the observed higher risk of overshoot and the significant increase in efficacy when shortening its administration interval.Trial registrationClinicalTrials.gov NCT01666301.

The neuroanatomical model of post-stroke depression: towards a change of focus?

One third of all stroke survivors develop post-stroke depression (PSD). Depressive symptoms adversely affect rehabilitation and significantly increase risk of death in the post-stroke period. One of the theoretical views on the determinants of PSD focuses on psychosocial factors like disability and social support. Others emphasize biologic mechanisms such as disruption of biogenic amine neurotransmission and release of proinflammatory cytokines. The "lesion location" perspective attempts to establish a relationship between localization of stroke and occurrence of depression, but empirical results remain contradictory. These divergences are partly related to the fact that neuroimaging methods, unlike neuropathology, are not able to assess precisely the full extent of stroke-affected areas and do not specify the different types of vascular lesions. We provide here an overview of the known phenomenological profile and current pathogenic hypotheses of PSD and present neuropathological data challenging the classic "single-stroke"-based neuroanatomical model of PSD. We suggest that vascular burden due to the chronic accumulation of small macrovascular and microvascular lesions may be a crucial determinant of the development and evolution of PSD.

Spinal cord T-cell infiltration in the spared nerve injury model of neuropathic pain: a time course study

Background : Numerous studies have shown that immune cells infiltrate the spinal cord after peripheral nerve injury and that they play a major contribution to sensory hypersensitivity in rodents. In particular, the role of monocyte-derived cells and T lymphocytes seems to be prominent in this process. This exciting new perspective in research on neuropathic pain opens many different areas of work, including the understanding of the function of these cells and how they impact on neural function. However, no systematic description of the time course or cell types that characterize this infiltration has been published yet, although this seems to be the rational first step of an overall understanding of the phenomenon. Objective : Describe the time course and cell characteristics of T lymphocyte infiltration in the spinal cord in the Spared Nerve Injury (SNI) model of neuropathic pain in rats. Methods : Collect of lumbar spinal cords of rats at days 2, 7, 21 and 40 after SNI or sham operation (n=4). Immunofluorescence detecting different proteins of T cell subgroups (CD2+CD4+, CD2+CD8+, Th1 markers, Th2 markers, Th17 markers). Quantification of the infiltration rate of the different subgroups. Expected results : First, we expect to see an infiltration of T cells in the spinal cord ipsilateral to nerve injury, higher in SNI rats than in sham animals. Second, we anticipate that different subtypes of T cells penetrate at different time points. Finally, the number of T lymphocytes are expected to decrease at the latest time point, showing a resolution of the process underlying their infiltrating the spinal cord in the first place. Impact : A systematic description of the infiltration of T cells in the spinal cord after peripheral nerve injury is needed to have a better understanding of the role of immune cells in neuropathic pain. The time course that we want to establish will provide the scientific community with new perspectives. First, it will confirm that T cells do indeed infiltrate the spinal cord after SNI in rats. Second, the type of T cells infiltrating at different time points will give clues about their function, in particular their inflammatory or anti-inflammatory profile. From there on, other studies could be lead, investigating the functional side of the specific subtypes put to light by us. Ultimately, this could lead to the discovery of new drugs targeting T cells or their infiltration, in the hope of improving neuropathic pain.

Inhibition of the Kit Ligand/c-Kit Axis Attenuates Metastasis in a Mouse Model Mimicking Local Breast Cancer Relapse after Radiotherapy.

PURPOSE: Local breast cancer relapse after breast-saving surgery and radiotherapy is associated with increased risk of distant metastasis formation. The mechanisms involved remain largely elusive. We used the well-characterized 4T1 syngeneic, orthotopic breast cancer model to identify novel mechanisms of postradiation metastasis. EXPERIMENTAL DESIGN: 4T1 cells were injected in 20 Gy preirradiated mammary tissue to mimic postradiation relapses, or in nonirradiated mammary tissue, as control, of immunocompetent BALB/c mice. Molecular, biochemical, cellular, histologic analyses, adoptive cell transfer, genetic, and pharmacologic interventions were carried out. RESULTS: Tumors growing in preirradiated mammary tissue had reduced angiogenesis and were more hypoxic, invasive, and metastatic to lung and lymph nodes compared with control tumors. Increased metastasis involved the mobilization of CD11b(+)c-Kit(+)Ly6G(high)Ly6C(low)(Gr1(+)) myeloid cells through the HIF1-dependent expression of Kit ligand (KitL) by hypoxic tumor cells. KitL-mobilized myeloid cells homed to primary tumors and premetastatic lungs, to give rise to CD11b(+)c-Kit(-) cells. Pharmacologic inhibition of HIF1, silencing of KitL expression in tumor cells, and inhibition of c-Kit with an anti-c-Kit-blocking antibody or with a tyrosine kinase inhibitor prevented the mobilization of CD11b(+)c-Kit(+) cells and attenuated metastasis. C-Kit inhibition was also effective in reducing mobilization of CD11b(+)c-Kit(+) cells and inhibiting lung metastasis after irradiation of established tumors. CONCLUSIONS: Our work defines KitL/c-Kit as a previously unidentified axis critically involved in promoting metastasis of 4T1 tumors growing in preirradiated mammary tissue. Pharmacologic inhibition of this axis represents a potential therapeutic strategy to prevent metastasis in breast cancer patients with local relapses after radiotherapy. Clin Cancer Res; 18(16); 4365-74. ©2012 AACR.

High-resolution three-dimensional aortic magnetic resonance angiography and quantitative vessel wall characterization of different atherosclerotic stages in a rabbit model

PURPOSE: Atherosclerosis results in a considerable medical and socioeconomic impact on society. We sought to evaluate novel magnetic resonance imaging (MRI) angiography and vessel wall sequences to visualize and quantify different morphologic stages of atherosclerosis in a Watanabe hereditary hyperlipidemic (WHHL) rabbit model. MATERIAL AND METHODS: Aortic 3D steady-state free precession angiography and subrenal aortic 3D black-blood fast spin-echo vessel wall imaging pre- and post-Gadolinium (Gd) was performed in 14 WHHL rabbits (3 normal, 6 high-cholesterol diet, and 5 high-cholesterol diet plus endothelial denudation) on a commercial 1.5 T MR system. Angiographic lumen diameter, vessel wall thickness, signal-/contrast-to-noise analysis, total vessel area, lumen area, and vessel wall area were analyzed semiautomatically. RESULTS: Pre-Gd, both lumen and wall dimensions (total vessel area, lumen area, vessel wall area) of group 2 + 3 were significantly increased when compared with those of group 1 (all P < 0.01). Group 3 animals had significantly thicker vessel walls than groups 1 and 2 (P < 0.01), whereas angiographic lumen diameter was comparable among all groups. Post-Gd, only diseased animals of groups 2 + 3 showed a significant (>100%) signal-to-noise ratio and contrast-to-noise increase. CONCLUSIONS: A combination of novel 3D magnetic resonance angiography and high-resolution 3D vessel wall MRI enabled quantitative characterization of various atherosclerotic stages including positive arterial remodeling and Gd uptake in a WHHL rabbit model using a commercially available 1.5 T MRI system.

Constraining ACT-R models of decision strategies: An experimental paradigm

It has been repeatedly debated which strategies people rely on in inference. These debates have been difficult to resolve, partially because hypotheses about the decision processes assumed by these strategies have typically been formulated qualitatively, making it hard to test precise quantitative predictions about response times and other behavioral data. One way to increase the precision of strategies is to implement them in cognitive architectures such as ACT-R. Often, however, a given strategy can be implemented in several ways, with each implementation yielding different behavioral predictions. We present and report a study with an experimental paradigm that can help to identify the correct implementations of classic compensatory and non-compensatory strategies such as the take-the-best and tallying heuristics, and the weighted-linear model.

Navigator-gated free-breathing 3D balanced FFE projection renal MRA: Comparison with contrast-enhanced breath-hold 3D MRA in a swine model.

A cardiac-triggered, free-breathing, 3D balanced FFE projection renal MR angiography (MRA) technique with a 2D pencil beam aortic labeling pulse for selective aortic spin tagging was developed. For respiratory motion artifact suppression during free breathing, a prospective real-time navigator was implemented for renal MRA. Images obtained with the new approach were compared with standard contrast-enhanced (CE) 3D breath-hold MRA in seven swine. Signal properties and vessel visualization were analyzed. With the presented technique, high-resolution, high-contrast renal projection MRA with superior vessel length visualization (including a greater visible number of distal branches of the renal arteries) compared to standard breath-hold CE-MRA was obtained. The present results warrant clinical studies in patients with renal artery disease.

Selective in vivo visualization of immune-cell infiltration in a mouse model of autoimmune myocarditis by fluorine-19 cardiac magnetic resonance.

BACKGROUND: The goal of this study was to characterize the performance of fluorine-19 ((19)F) cardiac magnetic resonance (CMR) for the specific detection of inflammatory cells in a mouse model of myocarditis. Intravenously administered perfluorocarbons are taken up by infiltrating inflammatory cells and can be detected by (19)F-CMR. (19)F-labeled cells should, therefore, generate an exclusive signal at the inflamed regions within the myocardium. METHODS AND RESULTS: Experimental autoimmune myocarditis was induced in BALB/c mice. After intravenous injection of 2×200 µL of a perfluorocarbon on day 19 and 20 (n=9) after immunization, in vivo (19)F-CMR was performed at the peak of myocardial inflammation (day 21). In 5 additional animals, perfluorocarbon combined with FITC (fluorescein isothiocyanate) was administered for postmortem immunofluorescence and flow-cytometry analyses. Control experiments were performed in 9 animals. In vivo (19)F-CMR detected myocardial inflammation in all experimental autoimmune myocarditis-positive animals. Its resolution was sufficient to identify even small inflammatory foci, that is, at the surface of the right ventricle. Postmortem immunohistochemistry and flow cytometry confirmed the presence of perfluorocarbon in macrophages, dendritic cells, and granulocytes, but not in lymphocytes. The myocardial volume of elevated (19)F signal (rs=0.96; P<0.001), the (19)F signal-to-noise ratio (rs=0.92; P<0.001), and the (19)F signal integral (rs=0.96; P<0.001) at day 21 correlated with the histological myocarditis severity score. CONCLUSIONS: In vivo (19)F-CMR was successfully used to visualize the inflammation specifically and robustly in experimental autoimmune myocarditis, and thus allowed for an unprecedented insight into the involvement of inflammatory cells in the disease process.

Prospective sampling based on model ensembles improves the detection of rare species

Identifying the geographic distribution of populations is a basic, yet crucial step in many fundamental and applied ecological projects, as it provides key information on which many subsequent analyses depend. However, this task is often costly and time consuming, especially where rare species are concerned and where most sampling designs generally prove inefficient. At the same time, rare species are those for which distribution data are most needed for their conservation to be effective. To enhance fieldwork sampling, model-based sampling (MBS) uses predictions from species distribution models: when looking for the species in areas of high habitat suitability, chances should be higher to find them. We thoroughly tested the efficiency of MBS by conducting an important survey in the Swiss Alps, assessing the detection rate of three rare and five common plant species. For each species, habitat suitability maps were produced following an ensemble modeling framework combining two spatial resolutions and two modeling techniques. We tested the efficiency of MBS and the accuracy of our models by sampling 240 sites in the field (30 sitesx8 species). Across all species, the MBS approach proved to be effective. In particular, the MBS design strictly led to the discovery of six sites of presence of one rare plant, increasing chances to find this species from 0 to 50%. For common species, MBS doubled the new population discovery rates as compared to random sampling. Habitat suitability maps coming from the combination of four individual modeling methods predicted well the species' distribution and more accurately than the individual models. As a conclusion, using MBS for fieldwork could efficiently help in increasing our knowledge of rare species distribution. More generally, we recommend using habitat suitability models to support conservation plans.

Electric dipole polarizability in 208Pb: insights from the droplet model

We study the electric dipole polarizability α D in 208 Pb based on the predictions of a large and representative set of relativistic and nonrelativistic nuclear mean-field models. We adopt the droplet model as a guide to better understand the correlations between α D and other isovector observables. Insights from the droplet model suggest that the product of α D and the nuclear symmetry energy at saturation density J is much better correlated with the neutron skin thickness r np of 208 Pb than the polarizability alone. Correlations of α D J with r np and with the symmetry energy slope parameter L suggest that α D J is a strong isovector indicator. Hence, we explore the possibility of constraining the isovector sector of the nuclear energy density functional by comparing our theoretical predictions against measurements of both α D and the parity-violating asymmetry in 208 Pb. We find that the recent experimental determination of α D in 208 Pb in combination with the range for the symmetry energy at saturation density J = [31 ± (2) est] MeV suggests r np (208 Pb) = 0 . 165 ± (0 . 009) expt ± (0 . 013) theor ± (0.021) est fm and L = 43 ± (6) expt ± (8) theor ± (12) est MeV