The evolution of the footwall to the Ronda subcontinental mantle peridotites: insights from the Nieves Unit (western Betic Cordillera)

Strongly heterogeneous deformation and extreme metamorphic gradients characterize the dominantly carbonate Nieves Unit in the footwall to the Ronda mantle extrusion wedge in the western Betic Cordillera. A well-developed foliation and mineral lineation, together with isoclinal intrafolial folds, occur in silicate-bearing, calcite or dolomite marbles within a c. 1.5 km thick metamorphic aureole underlying the peridotites. For the inferred maximum pressure of 300 MPa, petrological investigations allow us to define temperature ranges for the main zones of the metamorphic aureole: >510 °C (probably c. 700 °C) for the forsterite zone; 510–430 °C for the diopside zone; 430–360 °C for the tremolite zone; 360–330 °C for the phlogopite zone. Field structural analysis integrated with petrological, microstructural and electron backscatter diffraction textural data document large finite strains consistent with general shear within the metamorphic aureole, associated with NW-directed thrusting of the peridotites. On the other hand, post-kinematic silicate growth suggests that heat diffusion from the high-temperature peridotites continued after the final emplacement of the Ronda mantle extrusion wedge, leading to final zoning of the metamorphic aureole and to local partial annealing of calcite marble textures, particularly in the highest-temperature zone of the thermally softened footwall carbonates. Following substantial cooling, renewed crustal shortening affected the whole Nieves Unit, resulting in widespread development of NE–SW-trending meso-scale folds

Breast cancer Multiple cycles of dose-intensive chemotherapy with repeated stem cell support as induction treatment in metastatic breast cancer: a feasibility study

Summary: The purpose of this trial was to study feasibility and tolerance of a dose-intensive multicyclic alternating induction chemotherapy with repeated stem cell support in a series of 43 metastatic breast cancer patients. ades. Extensive literature reviews by Hryniuk et al 1,2 have found dose intensity to be correlated with response rate and survival. This effect has been considered in the rationale of many clinical trials that attempted to improve long-term survival in metastatic BC by delivering single courses of high-dose chemotherapy (HDC). Despite some promising data derived from phase II trials, results of the randomized studies published thus far have failed to show a sound clinical benefit for single autografts. 8 Multicyclic treatment schemes appear to take advantage of the inherent time-dependant responsiveness of most cancer tissues. Autologous peripheral blood stem cell infusions have been extensively used to support single courses of HDC. Nonetheless, their possible use in programs of multicyclic non-myeloablative dose-intense chemotherapy has been little explored. Materials and methods Women with histologically proven metastatic BC were evaluated for study entry. An ECOG performance status of 0-1, age less than 65 years, and no evidence of cardiac, pulmonary, liver or renal impairment were required. All patients gave written informed consent according to institutional policy before entering the study. Patients presenting with brain metastases, leptomeningeal disease, or bone marrow involvement, as well as patients previousl

Tumor and Microenvironment Evolution during Immunotherapy with Nivolumab.

The mechanisms by which immune checkpoint blockade modulates tumor evolution during therapy are unclear. We assessed genomic changes in tumors from 68 patients with advanced melanoma, who progressed on ipilimumab or were ipilimumab-naive, before and after nivolumab initiation (CA209-038 study). Tumors were analyzed by whole-exome, transcriptome, and/or T cell receptor (TCR) sequencing. In responding patients, mutation and neoantigen load were reduced from baseline, and analysis of intratumoral heterogeneity during therapy demonstrated differential clonal evolution within tumors and putative selection against neoantigenic mutations on-therapy. Transcriptome analyses before and during nivolumab therapy revealed increases in distinct immune cell subsets, activation of specific transcriptional networks, and upregulation of immune checkpoint genes that were more pronounced in patients with response. Temporal changes in intratumoral TCR repertoire revealed expansion of T cell clones in the setting of neoantigen loss. Comprehensive genomic profiling data in this study provide insight into nivolumab\u27s mechanism of action

Variscan tectonics in the Malaguide Complex (Betic Cordillera, southern Spain): stratigraphic and structural Alpine vs. Pre-Alpine constraints from the Ardales area (Province of Malaga). Part II: Structure

Unraveling structural features related to different orogenic cycles is fundamental for a better understanding of collisional orogens, particularly concerning the role of structural inheritance and extent of crustal reworking. In the Internal Domains of the Betic Cordillera, the geometry and kinematics of pre-Alpine contractional deformation in the Paleozoic basements are rather poorly known. At Ardales, a strongly deformed area corresponding to part of the Alpine suture zone of the Betic Cordillera, the Malaguide Complex consists of two distinct, superposed Alpine tectonic units, including both Paleozoic basement and Mesozoic-Tertiary cover rocks. Within the Alpine footwall unit, stratigraphic data document a tectonic superposition of two subunits made of different Paleozoic successions, which was later fossilized by Triassic redbeds. Structural analysis indicates that the contact between these subunits is an east-directed overthrust and that the internal structure of the lower subunit is consistent with bulk noncoaxial strain dominated by top-to-the-E shearing. These features show a marked contrast with the well-known Alpine nappe transport direction to the N-NW, with tectonic features developed along the Internal-External Domain boundary and with the structural trends obtained from the analysis of Mesozoic-Tertiary Malaguide rocks of the area. This study demonstrates that east-directed thrusting and shearing within Paleozoic Malaguide rocks resulted from Variscan tectonics and that careful, detailed, and integrated stratigraphic and structural analysis is necessary to avoid confusion between older and newer orogenic cycles in the Internal Domain Units of the Betic Cordillera