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Hematologic spread of carcinoma results in incurable metastasis; yet, the basic characteristics and travel mechanisms of cancer cells in the bloodstream are unknown. We have established a fluid phase biopsy approach that identifies circulating tumor cells (CTCs) without using surface protein-based enrichment and presents them in sufficiently high definition (HD) to satisfy diagnostic pathology image quality requirements. This “HD-CTC” assay finds >5 HD-CTCs/mL of blood in 80% of patients with metastatic prostate cancer (n=20), in 70% of patients with metastatic breast cancer (n=30), in 50% of patients with metastatic pancreatic cancer (n=18), and in 0% of normal controls (n=15). Additionally, it finds HD-CTC clusters ranging from 2 HDCTCs to greater than 30 HD-CTCs in the majority of these cancer patients. This initial validation of an enrichment-free assay demonstrates our ability to identify significant numbers of HD-CTCs in a majority of patients with prostate, breast and pancreatic cancers.

Mica and hornblende K‐Ar and Ar‐Ar data are presented from each of the three crustal components of the Himalayan collision zone in North Pakistan: the Asian plate, the Kohistan Island Arc, and the Indian plate. Together with U‐Pb and Rb‐Sr data published elsewhere these new data (1) date the age of suturing along the Northern Suture, which separates Kohistan from Asia, at 102–85 Ma; (2) establish that the basic magmatism in Kohistan, which postdates collision along the Northern Suture, predates 60 Ma, and that the later granite magmatism spanned a range of 60–25 Ma; (3) show that uplift amounts within Kohistan are greater toward the Nanga Parbat syntaxis than away from it and that rate of uplift near the syntaxis increased over the last 20 Ma to a current figure of about 5.5 mm a year; (4) show that much of southern Kohistan had cooled to below 500°C by 80 Ma and that the major deformation which imbricated Kohistan probably predated 80 Ma and certainly predated 60 Ma and was related to the Kohistan‐Asia collision rather than the Kohistan‐India one; (5) imply that uplift along the Hunza Shear in the Asian plate together with imbrication of the metamorphics in its hanging wall took place at about 10 Ma and was associated with breakback thrusting in the hanging wall of the Main Mantle Thrust; (6) suggest that the Indian plate has a lengthy pre‐Himalayan history with an early metamorphism at about 1900 Ma, major magmatism at 500–550 Ma and early Jurassic lithospheric extension or inversion; and (7) show that the Indian plate rocks were metamorphosed shortly after the collision within Kohistan, which occurred at circa 50 Ma, and subsequently cooled back through 500°C at circa 38 Ma and 300°C at 30–35 Ma with ages of cooling through 200° and 100°C (as determined by fission track data) locally controlled by Nanga Parbat related uplift tectonics.

Summary This overview summarizes aspects of 150 years of research in Alpine tectonics and in particular introduces the tectonic setting for the more detailed papers in this volume. The Alpine Mesozoic ocean, Tethys, formed as a large elongate pull-apart basin in the Jurassic, as a consequence of the opening of the Atlantic and of the movement of Africa towards the east relative to a fixed Europe. The NNE trending Tethys was bounded by WNW trending transforms, by the European/Iberian margin in the W and by the Adriatic promontory of Africa in the E, and its shape determined the present day configuration of the arcs of the Alpine chain. The closing of this ocean and the collision tectonics began during the Cretaceous, as Africa moved to the NE relative to Europe and as the N Atlantic gradually opened, to drive Iberia and the southern part of the European plate to the E. Subduction of oceanic crust and adjacent continental crust led to high pressure metamorphism of Cretaceous age. Ophiolites were obducted over the southern continental margin, but after collision the shear sense reversed so that the Austro-Alpine nappes of the African Adriatic promontory overthrust Europe in a WNW direction. During the main Tertiary deformation the overall anticlockwise rotation of Africa led to a change-over from N to NW and WNW-directed collisional structures. The E-W striking sector of the Alps in Switzerland and Austria is therefore a diffuse transpressive dextral shear belt, approximately reworking the northern transform boundary of Tethys, modifying it by compression related to the rotation of the African Adriatic promontory. Approximately 250 km of European lithosphere were involved in the building of the western Alps. As Alpine nappes consist largely of rock material confined to the upper crust, a large amount of lower crust and lithospheric mantle of the two continental blocks must be duplicated and/or subducted during the Alpine collision history.