Clinical implications of changing thyroglobulin and antithyroglobulin antibodies analytical methods in the follow-up of patients with differentiated thyroid carcinoma.

BACKGROUND AND AIMS: Patients' response to treatment in differentiated thyroid cancer (DTC) is classified according to serum thyroglobulin concentrations (Tg), usually using the American Thyroid Association guidelines and considering potential interfering anti-thyroglobulin antibodies (Ab-Tg). We aim to evaluate the clinical implications of changing Tg and Ab-Tg quantification method. MATERIAL AND METHODS: Tg and Ab-Tg were quantified in 82 serum samples (60 from DTC patients) by Elecsys and Access immunoassays. RESULTS: Elecsys immunoassay rendered higher values of Tg than Access: mean bias 5.03 ng/mL (95%CI:-14.14-24.21). In DTC patients, there was an almost perfect agreement for response classification (kappa index = 0.833). Discrepancies appeared in patients with undetermined response, with a more tendency to subclassification with Access. Ab-Tg showed a poor correlation (r = 0.5394). When Elecsys cut-off was reduced to 43 IU/mL, agreement for positive/negative classification improved from a kappa index of 0.607 to 0.650. Prospective study with personalized follow-up showed that only 6.3% of Tg results required an analytical confirmation, being confirmed 93% of them. CONCLUSIONS: Despite the biases observed, clinical impact of an analytical change is minimal in patients' management. However, cautious and personalized follow-up period after the change is still mandatory, especially in patients with Tg levels between 0.2 and 1 ng/mL.

Reassessment of the human mandible from Banyoles (Girona, Spain).

Since the discovery of a human mandible in 1887 near the present-day city of Banyoles, northeastern Spain, researchers have generally emphasized its archaic features, including the lack of chin structures, and suggested affinities with the Neandertals or European Middle Pleistocene (Chibanian) specimens. Uranium-series and electron spin resonance dating suggest the mandible dates to the Late Pleistocene (Tarantian), approximately ca. 45-66 ka. In this study, we reassessed the taxonomic affinities of the Banyoles mandible by comparing it to samples of Middle Pleistocene fossils from Africa and Europe, Neandertals, Early and Upper Paleolithic modern humans, and recent modern humans. We evaluated the frequencies and expressions of morphological features and performed a three-dimensional geometric morphometric analysis on a virtual reconstruction of Banyoles to capture overall mandibular shape. Our results revealed no derived Neandertal morphological features in Banyoles. While a principal component analysis based on Euclidean distances from the first two principal components clearly grouped Banyoles with both fossil and recent Homo sapiens individuals, an analysis of the Procrustes residuals demonstrated that Banyoles did not fit into any of the comparative groups. The lack of Neandertal features in Banyoles is surprising considering its Late Pleistocene age. A consideration of the Middle Pleistocene fossil record in Europe and southwest Asia suggests that Banyoles is unlikely to represent a late-surviving Middle Pleistocene population. The lack of chin structures also complicates an assignment to H. sapiens, although early fossil H. sapiens do show somewhat variable development of the chin structures. Thus, Banyoles represents a non-Neandertal Late Pleistocene European individual and highlights the continuing signal of diversity in the hominin fossil record. The present situation makes Banyoles a prime candidate for ancient DNA or proteomic analyses, which may shed additional light on its taxonomic affinities.

The timing and spatiotemporal patterning of Neanderthal disappearance.

The timing of Neanderthal disappearance and the extent to which they overlapped with the earliest incoming anatomically modern humans (AMHs) in Eurasia are key questions in palaeoanthropology. Determining the spatiotemporal relationship between the two populations is crucial if we are to understand the processes, timing and reasons leading to the disappearance of Neanderthals and the likelihood of cultural and genetic exchange. Serious technical challenges, however, have hindered reliable dating of the period, as the radiocarbon method reaches its limit at ∼50,000 years ago. Here we apply improved accelerator mass spectrometry (14)C techniques to construct robust chronologies from 40 key Mousterian and Neanderthal archaeological sites, ranging from Russia to Spain. Bayesian age modelling was used to generate probability distribution functions to determine the latest appearance date. We show that the Mousterian ended by 41,030-39,260 calibrated years bp (at 95.4% probability) across Europe. We also demonstrate that succeeding 'transitional' archaeological industries, one of which has been linked with Neanderthals (Châtelperronian), end at a similar time. Our data indicate that the disappearance of Neanderthals occurred at different times in different regions. Comparing the data with results obtained from the earliest dated AMH sites in Europe, associated with the Uluzzian technocomplex, allows us to quantify the temporal overlap between the two human groups. The results reveal a significant overlap of 2,600-5,400 years (at 95.4% probability). This has important implications for models seeking to explain the cultural, technological and biological elements involved in the replacement of Neanderthals by AMHs. A mosaic of populations in Europe during the Middle to Upper Palaeolithic transition suggests that there was ample time for the transmission of cultural and symbolic behaviours, as well as possible genetic exchanges, between the two groups.

Chronological and environmental context of the Middle Pleistocene human tooth from Mollet Cave (Serinyà, NE Iberian Peninsula).

Mollet Cave is a small cave situated in Serinyà (north-east Iberian Peninsula). It was excavated in 1947-48, 1958 and 1972 by Josep M. Corominas. An archaic human molar comes from its base layer (Layer 5). Up till now, this layer has only been dated based on a relative and imprecise chronology of macromammals and the archaeostratigraphic evidence from the early excavations. Recent excavations, conducted between 2001 and 2005, have made it possible to ascertain more precisely the archaeological and palaeontological contents of Mollet Cave, gather microvertebrates, and collect samples for radiometric dating. The aim of this paper is to present the absolute dating of Layer 5, as well as its palaeo environmental and climatic characterisation. The macromammal assemblage seems to have been the result of accumulations produced by the most abundant carnivore, the hyena, which would have used the cave as a den. The results obtained using uranium-series disequilibrium dating ascribe to Layer 5 an age of ca. 215 ka (thousands of years ago), which would correspond to MIS 7. The faunal association suggests a landscape formed by an open and humid woodland characteristic of an interstadial phase, which would have been an environment well suited to sustaining both hyenas and human groups.

ESR and U-series analyses of enamel and dentine fragments of the Banyoles mandible.

The Banyoles mandible presents a puzzle. Its anatomy has been described as pre-Neandertal, but the travertine in which it was found has been dated to 45,000 +/- 4000 years. By this time, any pre-Neandertals had supposedly been absent from the European fossil record for more than 100,000 years. It was therefore proposed that the age of the travertine may represent a minimum age estimate, with the mandible possibly having been reworked from older deposits. We carried out a non-destructive ESR analysis of an enamel fragment removed from a molar and performed a series of in situ laser ablation U-series analyses on dentine fragments adjacent to the enamel piece. The analyses resulted in an apparent combined ESR-U-series age of 66,000 +/- 7000 years. The encasing travertine matrix was also analyzed for U-series isotopes and showed signs of U-mobilization. It cannot be excluded that the travertine matrix is older than the previously determined age. If the mandible was not reworked, then the combined ESR-U-series result on the tooth enamel would give its best age estimate. If, on the other hand, the mandible was reworked from another deposit, the actual ESR-U-series age will depend on the external dose rate from the previous matrix and the depth of its burial, which controls the degree of the attenuation of the cosmic dose rate over time. Considering a range of possible burial histories, the mean age of the mandible would lie somewhere between the combined ESR-U-series age and the previously determined age of the travertine matrix. Regarding the morphology of the mandible, a review of its features in the context of larger Neandertal samples indicates that the anatomy of the specimen is not incompatible with such a young age determination, although it further highlights morphological variation in the late Neandertal sample.