In order to search for sequence variants conferring risk of thyroid cancer we conducted a genomewide association study in 192 and 37,196 Icelandic cases and controls, respectively, followed by a replication study in individuals of European descent. Here we show that two common variants, located on 9q22.33 and 14q13.3, are associated with the disease. Overall, the strongest association signals were observed for rs965513 on 9q22.33 (OR = 1.75; P = 1.7 × 10 −27 ) and rs944289 on 14q13.3 (OR = 1.37; P = 2.0 × 10 −9 ). The gene nearest to the 9q22.33 locus is FOXE1 (TTF2) and NKX2-1 (TTF1) is among the genes located at the 14q13.3 locus. Both variants contribute to an increased risk of both papillary and follicular thyroid cancer. Approximately 3.7% of individuals are homozygous for both variants, and their estimated risk of thyroid cancer is 5.7-fold greater than that of noncarriers. In a study on a large sample set from the general population, both risk alleles are associated with low concentrations of thyroid stimulating hormone (TSH), and the 9q22.33 allele is associated with low concentration of thyroxin (T 4 ) and high concentration of triiodothyronine (T 3 ).Thyroid carcinoma is the most common endocrine malignancy, and its incidence in industrialized countries has been rising over the past few decades: at present, its incidence is 4.9 and 14.1 per 100,000 in the United States for males and females of European ancestry, respectively (see URLs section in Methods). It has been determined that the risk of thyroid cancer has a greater genetic component than the risk of any other cancer, and the effect has been shown to extend beyond the nuclear family 1-3 . The risk has been reported to be highest for first-degree male relatives of male probands but lowest for first-degree female relatives of female probands 4 . Not much is known about variants in the sequence of the genome that affect the risk of thyroid cancer. However, recently variants at 1p12, 8q24 and in the premiR146a at 5q33 have been implicated in the disease 5-8 .Thyroid cancer is classified histologically into four main groups: papillary (PTC), follicular (FTC), medullary (MTC) and undifferentiated or anaplastic thyroid carcinomas. Most of all thyroid tumors are PTC (80-85%) or FTC (10-15%) 9,10 . Among established risk factors for FTC is deficiency in iodine intake, and for PTC the risk factors include ionizing radiation, nodular disease of the thyroid as well as family history 9 . Medullary thyroid cancer is a part of the multiple endocrine neoplasia type 2 syndrome (MEN2) and accounts for about 1-3% of all thyroid cancer cases. Its pathogenesis can mainly be explained by mutations in the RET oncogene 11 . Anaplastic thyroid cancer accounts for between 1% and 5% of all carcinomas of the thyroid. This subphenotype is one of the most aggressive of all human malignancies, but little is known about its pathogenesis 12 .In Iceland, the annual incidence of thyroid cancer is similar to that in the United States, at 4.6 and 12.1 per 100,000 for males and fe...

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Systematic excavation and multidisciplinary research undertaken over three decades have deepened our understanding of the early Palaeolithic archaeology at Cueva Negra del Estrecho del Río Quípar (Caravaca de la Cruz, Murcia, Spain). New results from biochronology and combined ESR and U-series dating corroborate previous magnetostratigraphy, placing the entire excavated sequence between the Jaramillo sub-chron and the Matuyama-Brunhes boundary (i.e., ca. 990-772 thousand years ago [ka]); palaeontological and palynological findings reflect temperate environmental conditions. A bifacially-flaked limestone hand-axe was excavated one metre below the top of the Pleistocene sequence. The Equus cf. altidens tooth that provided the ESR estimate was excavated one metre below the hand-axe. Throughout its five-metre-deep sedimentary sequence, small nodules, fragments, and struck flakes make up the bulk of the Palaeolithic assemblage. Stratigraphical analysis points to undisturbed continuous sedimentary deposition above a layer of ashy sediment, encountered 4.5 m below the top of the Pleistocene sequence, which contained thermallyaltered bone and heat-shattered chert cores and flakes. Cueva Negra is among the earliest European sites with firm evidence of combustion..Introduction Context Geographical locationCueva Negra del Estrecho del Río Quípar is a large, north-facing, rock-shelter (ca. 10x10 m in area), in Upper Miocene (Tortonian) biocalcarenite rock, lying at 740 m above sea level, a.s.l. (38° 02' 12.5" N; 1° 53' 5.8" W) on the right bank 40 m above the Quípar River where it flows northwards from a one-kilometre-long gorge (the Estrecho, i.e., "the Narrows") below the hamlet of La Encarnación in Caravaca de la Cruz municipality (Murcia, Spain) (Figure 1). The Quípar is a tributary of the Segura River that reaches the Mediterranean Sea 110 km E of Cueva Negra, even though the cave lies only 70 km N of the Murcian coast. Important geological faults determine the alignment of tributaries in the Segura drainage basin. The Estrecho follows the sinistral reverse Quípar Fault, active since the Late Miocene (Messinian). Activity caused uplift of the right bank of the river, thereby saving from riverine erosion the fine-grained fluviatile sediments that had accumulated in Cueva Negra under conditions of low transport energy by intermittent overflow of an erstwhile swampy lake fed by the Quípar during the late Early Pleistocene. The Quípar enters the gorge at 725 m a.s.l. and leaves it at 690 m a.s.l.. The height of the land above sea level during the Early Pleistocene is unknown. The Upper Miocene (Tortonian) calcarenite formed under the Tethys Sea, arising to become a shoreline surface in the Upper Pliocene. Cueva Negra is a vestige of a trapezoidal endokarstic cavity that likely developed in relation to low-lying lagoons or lakes. LithostratigraphyThe fluviatile sediments inside Cueva Negra include clasts eroded from the cave roof and walls. Palaeolithic and faunal remains are present throughout the five-metre depth, implying...

RESUMENSe presentan los resultados preliminares de la excavación de un enterramiento múltiple en cueva que contiene restos de más de 1300 individuos, en lo que parece ser la representación completa de una población calcolítica de la segunda mitad del III milenio a.C. depositada durante un período continuado de unos 350-400 años. Una pequeña parte de esa población se acompaña de un ajuar que incluye, entre otros elementos, algunos elementos metáli-cos característicos del horizonte campaniforme. También se documenta el enterramiento de cánidos acompañando a diversos inhumados. El carácter excepcional del hallazgo y las circunstancias de la excavación han obligado a un desarrollo metodológico novedoso para este tipo de actuaciones. (1) No sería justo obviar la encomiable actitud y buena disposición del promotor de las obras en las que se localizó el yacimiento, D. Pedro Antonio Robles, quien no sólo paró inmediatamente la obra e informó del hallazgo a las autoridades sino que, más allá de su obligación como ciudadano, asumió la cubrición y cerramiento del yacimiento para su ulterior excavación, así como numerosos gastos directamente relacionados con los trabajos de campo, tanto de contratación de personal como de alojamiento de parte del equipo. ABSTRACT