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In this paper, an educational methodology based on collaborative and competitive learning is proposed. The suggested approach has been successfully applied to an undergraduate communication networks course, which is part of the core curriculum of the three-year degree in telecommunications engineering at the University of Valladolid in Spain. This methodology is supported by two tools: the Moodle wiki for the collaborative part and a competitive learning tool called QUESTOURnament, which has been created by the authors to encourage the development of students' inquiry, documentation, and critical analysis skills while raising the level of involvement and communication between students and teachers. This paper describes how the collaborative and competitive approaches were combined and how the activities were ordered in phases. This educational proposal has been validated with academic outcomes and students' feedback. (Contains 6 tables and 2 figures.)

This study presents an analysis of linear enamel hypoplasias (LEH) and plane-form defects (PFD) in the hominine dental sample from the Sima de los Huesos (SH) Middle Pleistocene site in Atapuerca (Spain). The SH sample comprises 475 teeth, 467 permanent and 8 deciduous, belonging to a minimum of 28 individuals. The method for recording PFD and LEH is discussed, as well as the definition of LEH. The prevalence of LEH and PFD in SH permanent dentition (unilateral total count) is 4.6% (13/280). Only one deciduous tooth (lower dc) showed an enamel disruption. Prevalence by individual ranges from 18.7-30%. The most likely explanation for the relatively low LEH and PFD prevalence in the SH sample suggests that the SH population exhibited a low level of develop- mental stress. The age at occurrence of LEH and PFD was determined by counting the number of perikymata between each lesion and the cervix of the tooth. Assuming a periodicity of nine days for the incremental lines, the majority of LEH in the SH sample occurred during the third year of life and may be related to the metabolic stress associated with weaning. [ABSTRACT FROM AUTHOR]

Human hearing differs from that of chimpanzees and most other anthropoids in maintaining a relatively high sensitivity from 2 kHz up to 4 kHz, a region that contains relevant acoustic information in spoken language. Knowledge of the auditory capacities in human fossil ancestors could greatly enhance the understanding of when this human pattern emerged during the course of our evolutionary history. Here we use a comprehensive physical model to analyze the influence of skeletal structures on the acoustic filtering of the outer and middle ears in five fossil human specimens from the Middle Pleistocene site of the Sima de los Huesos in the Sierra de Atapuerca of Spain. Our results show that the skeletal anatomy in these hominids is compatible with a human-like pattern of sound power transmission through the outer and middle ear at frequencies up to 5 kHz, suggesting that they already had auditory capacities similar to those of living humans in this frequency range. [ABSTRACT FROM AUTHOR]

This study presents quantitative data on the rates of anterior tooth wear in a Pleistocene human population. The data were obtained for the hominin sample of the Sima de los Huesos site in Atapuerca, Spain. The fossil record belongs to a minimum of 28 individuals of the same biological population, assigned to the species Homo heidelbergensis. We have estimated the original and the preserved crown height of the mandibular incisors (11 and 12) of 11 individuals, whose age at death can be ascertained from the mineralization stage and tooth eruption. Results provide a range of 0.2760.348 and 0.288-0.360 mm per year for the mean wear rate of the mandibular I1 and 12, respectively, in individuals ≈16-18 years old. These data suggest that incisors' crowns would be totally worn out toward the fifth decade of life. Thus, we expect the life expectancy of this population to be seriously limited. These data, which could be contrasted with results obtained on hominins at other sites, could be of interest for estimating the death age of adult individuals. [ABSTRACT FROM AUTHOR]

The author discusses the article by K. F. Otterbein on the cannibalism found in the TD6 level of the Gran Dolina site in Sierra de Atapuerca, Burgos, Spain. He notes the most interesting comment of Otterbein that focuses on the possibility of an armed confrontation between different political groups that occurred among early Pleistocene hominins. He also mentions about the case of exogenous cannibalism which resulted from the treatment of human bodies in TD6.

Abstract: Ascertaining the timing of the peopling of Europe, after the first out-of-Africa demographic expansion at the end of the Pliocene, is of great interest to paleoanthropologists. One of the earliest direct evidences for fossil hominins in western Europe comes from an infilled karstic cave site called Gran Dolina at Atapuerca, in a stratum ∼1.5m below the Brunhes–Matuyama (B–M) geomagnetic boundary (780ka) within lithostratigraphic unit TD6. However, most of the meters of fossil- and tool-bearing strata at Gran Dolina have been difficult to date. Therefore, we applied both thermoluminescence (TL) and infrared-stimulated-luminescence (IRSL) multi-aliquot dating methods to fine-silt fractions from sediment samples within Gran Dolina and the nearby Galería cave site. We also applied these methods to samples from the present-day surface soils on the surrounding limestone hill slopes to test the luminescence-clock-zeroing-by-daylight assumption. Within the uppermost 4m of the cave deposits at Gran Dolina, TL and paired TL and IRSL ages range stratigraphically from 198±19ka to 244±26ka. Throughout Gran Dolina, all luminescence results are stratigraphically self-consistent and, excepting results from two stratigraphic units, are consistent with prior ESR-U-series ages from progressively deeper strata. Thermoluminescence ages culminate at 960±120ka approximately 1m below the 780ka B–M boundary. At Galería, with one exception, TL and IRSL ages range stratigraphically downward from 185±26ka to 503±95ka at the base of the lowermost surface-inwash facies. These results indicate that TL and (sometimes) IRSL are useful dating tools for karstic inwash sediments older than ca. 100ka, and that a more accurate chronostratigraphic correlation is now possible among the main Atapuerca sites (Gran Dolina, Galería, Sima de los Huesos). Furthermore, the oldest TL age of ca. 960ka from Gran Dolina, consistent with biostratigraphic and paleomagnetic evidence, implies a probable numeric age of 900–950ka for the oldest hominin remains (∼0.8m below the TL sample). This age window suggests a correspondence to Marine Isotope Stage (MIS) 25, a relatively warm and humid interglaciation. [Copyright &y& Elsevier]

Background: Perioperative immunotherapy improves short-term outcomes in resectable non-small-cell lung cancer (NSCLC). We now report 5-year survival from the NADIM trial to assess its long-term benefit., Methods: NADIM was a multicentre, single-arm, phase 2 trial conducted across 18 hospitals in Spain. Patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had histologically or cytologically confirmed, treatment-naive, resectable stage IIIA NSCLC (American Joint Committee on Cancer, 7th edition criteria). The neoadjuvant treatment consisted of three cycles of intravenous paclitaxel (200 mg/m 2 ) and carboplatin (area under the curve 6 mg/mL per min) with nivolumab (360 mg). After surgery, 1 year of adjuvant treatment with intravenous nivolumab monotherapy was administered (240 mg every 2 weeks for 4 months, followed by 480 mg every 4 weeks for 8 months). The primary endpoint was 24-month progression-free survival, with 5-year progression-free survival and overall survival as secondary endpoints, assessed in the intention-to-treat population (ie, all patients who received neoadjuvant treatment). Toxicity profile was also assessed as a secondary endpoint. This trial is registered at ClinicalTrials.gov (NCT03081689) and is complete; this is the final report of the trial., Findings: Between April 26, 2017, and Aug 25, 2018, 51 patients were assessed for eligibility, of whom 46 comprised the intention-to-treat population (34 [74%] male and 12 [26%] female, median age 63 years [IQR 58-70]). Follow-up was concluded at 60 months (data cutoff July 11, 2023; median follow-up 60·0 months [IQR 60·0-60·0]). 5-year progression-free survival in the intention-to-treat population was 65·0% (95% CI 49·4-76·9), and overall survival was 69·3% (53·7-80·6). Disease progression occurred in 11 (24%) patients; 14 (30%) patients died, including nine (20%) from disease relapse and five (11%) from non-tumour-related causes. Treatment-related adverse events (TRAEs) of grade 3 or worse occurred in 14 (30%) of 46 patients during neoadjuvant treatment and in seven (19%) of 37 during adjuvant treatment. The most common grade 3 or worse TRAEs were increased lipase and febrile neutropenia (three [7%] each) during neoadjuvant treatment, and elevated serum lipase (four [7%]) and elevated serum amylase (three [8%]) during adjuvant treatment. Serious TRAEs included elevated serum lipase and neutropenia (one [2%] each) during neoadjuvant treatment, and elevated serum lipase (one [3%]) during adjuvant treatment. No treatment-related surgery delays, deaths, or unexpected long-term toxicities were reported., Interpretation: Perioperative chemoimmunotherapy showed a promising long-term benefit with no concerning safety data, reinforcing its use in resectable stage IIIA NSCLC., Funding: Bristol-Myers Squibb, Spanish Ministry of Science, Instituto de Salud Carlos III, European Union., Competing Interests: Declaration of interests MP reports non-financial support (reagents for T-cell receptor sequencing) from ThermoFisher Scientific; grants, consulting fees, and non-financial support from Bristol Myers Squibb, Roche, and AstraZeneca; and consulting fees from MSD and Takeda; outside the submitted work. EN reports grants from Roche, Pfizer, Bristol Myers Squibb, Merck, and Nanostring; consulting fees from Roche, Bristol Myers Squibb, Merck Sharpe & Dohme, Merck-Serono, Sanofi, Pfizer, Lilly, Amgen, Janssen, Daiichi-Sankyo, Boehringer-Ingelheim, AstraZeneca, Takeda, Sanofi, Pierre Fabre, Qiagen, and Bayer; payment of honoraria from Roche, Bristol Myers Squibb, Merck Sharpe & Dohme, Sanofi, Pfizer, Lilly, Amgen, Janssen, Daiichi-Sankyo, Boehringer-Ingelheim, AstraZeneca, Takeda, Sanofi, and Qiagen; support for attending meetings or travel from Takeda, MSD, Janssen, and Roche; and participation on advisory boards for Apollomics, Roche, and Pfizer. AI reports consulting fees from Pfizer, Amgen, and Astra Zeneca; payment for expert testimony from Bristol Myers Squibb, Roche, Pfizer, Astra Zeneca, and Takeda; support for attending meetings or travel from Roche, Takeda, and Pfizer; and participation on advisory boards for Roche and Bristol Myers Squibb. RG-C reports consulting fees from Bristol Myers Squibb, MSD, Roche, Pfizer, and AstraZeneca. MD reports consulting fees from AstraZeneca, Bristol Myers Squibb, MSD Oncology, Pfizer, Roche, and Takeda; and support for attending meetings or travel from AstraZeneca, MSD Oncology, Pfizer, and Takeda. BM reports consulting fees from Astra Zeneca and Amgen; payment or honoraria from Roche, Bristol Myers Squibb, and MSD; and support for attending meetings or travel from MSD and AstraZeneca. MM reports grants from Roche and Astra Zeneca; payment of honoraria from Roche, AstraZeneca, MSD, Pfizer, Helsinn, Cassen, Amgen, Janssen, Sanofi, Pierre Fabre, Bristol Myers Squibb, and Takeda; and support for attending meetings or travel from MSD, Roche, and AstraZeneca. DR-A reports honoraria for lectures from MSD, Roche, Bristol Myers Squibb, Novartis, Takeda, Lilly, and AstaZeneca; support for attending meetings or travel from Roche, MSD, Novartis, and Sanofi; and participation on advisory boards for Merck Sharpe & Dohme, Regeneron, Bristol Myers Squibb, GSK, and Lilly. AM-M reports consulting fees from AstraZeneca/MedImmune, Bristol Myers Squibb, F. Hoffmann La Roche, Merck Sharpe & Dohme, MSD Oncology, Pfizer, and Janssen; payment for expert testimony from AstraZeneca, MedImmune, Bristol Myers Squibb, and F. Hoffmann La Roche; support for attending meetings or travel from AstraZeneca, MedImmune, Bristol-Myers Squibb, F. Hoffmann La Roche, Merck Sharpe & Dohme, MSD Oncology, Pfizer, Janssen, and Lilly; and participation on advisory boards for AstraZeneca, MedImmune, Merck Sharpe & Dohme, F. Hoffmann La Roche, and Bristol-Myers Squibb. JdC reports consulting fees from AstraZeneca, Bristol Myers Squibb, Roche, MSD, Boehringer, Janssen, Lilly, Sanofi, Takeda, Pfizer, and GSK; support for attending meeting or travel from AstraZeneca, MSD, and Roche; participation on advisory boards for AstraZeneca, Bristol Myers Squibb, Roche, MSD, Glaxo, Janssen, and Gilea; and speaker's bureau fees from AstraZeneca/MedImmune, Bristol-Myers Squibb, F. Hoffmann La Roche, Merck Sharpe & Dohme, MSD Oncology, Pfizer, and Janssen. DG reports payment or honoraria from Astra Zeneca and Bristol Myers Squibb. VC reports consulting fees from Roche, AstraZeneca, MSD, Bristol Myers Squibb, Takeda, Sanofi, and Amgen; payment or honoraria from Roche, AstraZeneca, MSD, Bristol Myers Squibb, Takeda, SanofiI, and Amgen; and support for attending meetings or travel from AstraZeneca, Roche, MSD, and Takeda. RP reports payment or honoraria from Guardant Health and Pfizer; and support for attending meetings or travel from Merck Sharpe & Dohme; participation on an advisory board for AstraZeneca. AR reports payment or honoraria from Illumina, Health in Code, and ThermoFisher Scientific; support for attending meetings or travel from ThermoFisher Scientific, Bristol Myers Squibb Foundation, and Takeda; and advisory board participation for Takeda. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Recent advances in the treatment of locally advanced NSCLC have led to changes in the standard of care for this disease. For the selection of the best approach strategy for each patient, it is necessary the homogenization of diagnostic and therapeutic interventions, as well as the promotion of the evaluation of patients by a multidisciplinary oncology team., Objective: Development of an expert consensus document with suggestions for the approach and treatment of locally advanced NSCLC leaded by Spanish Lung Cancer Group GECP., Methods: Between March and July 2023, a panel of 28 experts was formed. Using a mixed technique (Delphi/nominal group) under the guidance of a coordinating group, consensus was reached in 4 phases: 1. Literature review and definition of discussion topics 2. First round of voting 3. Communicating the results and second round of voting 4. Definition of conclusions in nominal group meeting. Responses were consolidated using medians and interquartile ranges. The threshold for agreement was defined as 85% of the votes., Results: New and controversial situations regarding the diagnosis and management of locally advanced NSCLC were analyzed and reconciled based on evidence and clinical experience. Discussion issues included: molecular diagnosis and biomarkers, radiologic and surgical diagnosis, mediastinal staging, role of the multidisciplinary thoracic committee, neoadjuvant treatment indications, evaluation of response to neoadjuvant treatment, postoperative evaluation, and follow-up., Conclusions: Consensus clinical suggestions were generated on the most relevant scenarios such as diagnosis, staging and treatment of locally advanced lung cancer, which will serve to support decision-making in daily practice., (© 2024. The Author(s).)

Background: There are scarce data of the costs of non-small cell lung cancer (NSCLC) recurrence in Spain. The objective of this study is to assess the economic burden of disease recurrence, for both locoregional and/or metastatic relapses, after appropriate early-stage NSCLC treatment in Spain., Materials and Methods: A two-round consensus panel of Spanish oncologists and hospital pharmacists was conducted to collect information on patient's flow, treatments, use of healthcare resources and sick leaves in patients with relapsed NSCLC. A decision-tree model was developed to calculate the economic burden of disease recurrence after appropriate early-stage NSCLC. Both direct and indirect costs were considered. Direct costs included drug acquisition and healthcare resources costs. Indirect costs were estimated using the human-capital approach. Unit costs were obtained from national databases (euros of 2022). A multi-way sensitivity analysis was performed to provide a range to the mean values., Results: Among a cohort of 100 patients with relapsed NSCLC, 45 patients would have locoregional relapse (36.3 would eventually progress to metastasis and 8.7 would be considered in remission) and 55 patients would have metastatic relapse. Over time, 91.3 patients would experience a metastatic relapse (55 as first relapse and 36.6 after previous locoregional relapse). The overall cost incurred by the 100-patients cohort is €10,095,846 (€9,336,782 direct costs, €795,064 indirect costs). The average cost of a locoregional relapse is €25,194 (€19,658 direct costs, €5536 indirect costs), while the average cost a patient with metastasis who receives up to 4 lines of treatment is €127,167 (€117,328 direct, €9839 indirect)., Conclusions: To our knowledge, this is the first study that specifically quantifies the cost of relapse in NSCLC in Spain. Our findings shown that the overall cost of a relapse after appropriate treatment of early-stage NSCLC patients is substantial, and it increases considerably in the metastatic relapse setting, mainly due to the high cost and long duration of first-line treatments., (© 2023. The Author(s).)

Purpose: This Delphi panel study assessed the level of consensus between medical oncologists on the clinical management of patients with early-stage EGFR-mutated non-small cell lung cancer (NSCLC)., Methods: A modified two-round Delphi approach was used. A scientific committee comprised of medical oncologists developed an online questionnaire. Delphi panel experts rated their level of agreement with each questionnaire statement on a 9-point Likert scale. The questionnaire included 36 statements from 3 domains (clinical management of early-stage NSCLC: 15 statements; role of adjuvant therapy in early-stage NSCLC: 9 statements; and role of adjuvant therapy in early-stage NSCLC with sensitizing EGFR mutation: 12 statements)., Results: In round 1, consensus was reached for 24/36 statements (66.7%). Nine statements that did not achieve consensus after the first round were evaluated in round 2, and none of them reached consensus. Overall, 84.4% of the panelists agreed that EGFR mutation testing should be done after surgery. Consensus was not achieved on whether the implementation of EGFR mutation testing in resected early-stage NSCLC could limit the use of adjuvant osimertinib. The panelists recognized the rationale for the use of osimertinib in the adjuvant scenario (88%) and 72% agreed that it may change the treatment paradigm in stage IB-IIIA EGFR-mutated NSCLC. Consensus was not reached on the inconvenience of prolonged duration of osimertinib., Conclusions: This Delphi study provides valuable insights into relevant questions in the management of early-stage EGFR-mutated NSCLC. However, specific issues remain unresolved. The expert consensus emphasizes the role of adjuvant treatment with osimertinib in this scenario., (© 2022. The Author(s).)

Background: In an effort to contribute to overcoming the platinum resistance exhibited by most solid tumors, we performed an array of epigenetic approaches, integrating next-generation methodologies and public clinical data to identify new potential epi-biomarkers in ovarian cancer, which is considered the most devastating of gynecological malignancies., Methods: We cross-analyzed data from methylome assessments and restoration of gene expression through microarray expression in a panel of four paired cisplatin-sensitive/cisplatin-resistant ovarian cancer cell lines, along with publicly available clinical data from selected individuals representing the state of chemoresistance. We validated the methylation state and expression levels of candidate genes in each cellular phenotype through Sanger sequencing and reverse transcription polymerase chain reaction, respectively. We tested the biological role of selected targets using an ectopic expression plasmid assay in the sensitive/resistant tumor cell lines, assessing the cell viability in the transfected groups. Epigenetic features were also assessed in 189 primary samples obtained from ovarian tumors and controls., Results: We identified PAX9 and FKBP1B as potential candidate genes, which exhibited epigenetic patterns of expression regulation in the experimental approach. Re-establishment of FKBP1B expression in the resistant OVCAR3 phenotype in which this gene is hypermethylated and inhibited allowed it to achieve a degree of platinum sensitivity similar to the sensitive phenotype. The evaluation of these genes at a translational level revealed that PAX9 hypermethylation leads to a poorer prognosis in terms of overall survival. We also set a precedent for establishing a common epigenetic signature in which the validation of a single candidate, MEST, proved the accuracy of our computational pipelines., Conclusions: Epigenetic regulation of PAX9 and FKBP1B genes shows that methylation in non-promoter areas has the potential to control gene expression and thus biological consequences, such as the loss of platinum sensitivity. At the translational level, PAX9 behaves as a predictor of chemotherapy response to platinum in patients with ovarian cancer. This study revealed the importance of the transcript-specific study of each gene under potential epigenetic regulation, which would favor the identification of new markers capable of predicting each patient's progression and therapeutic response., (© 2021. The Author(s).)

Introduction: Pulmonary carcinoids are relatively rare neuroendocrine neoplasms, accounting for only 1-2% of malignant thoracic tumours. We describe our experience in the management and follow-up of such an infrequent tumour, with special emphasis on possible problems that might arise., Patients and Methods: We present a descriptive retrospective study of all patients diagnosed with carcinoid tumour between January 2013 and January 2018. Demographic, histological and clinical data were collected and analyzed. Survival was recorded. SPSS version 21 was used for the statistical analysis., Results: 42 patients with an average age of 66.26 years were included. The mean period of follow-up was 60 months and the average survival 59.12 months. The only statistically significant factor related to an improved survival time was tumour stage at diagnosis., Conclusion: Carcinoid tumours are infrequent, which makes the objective collecting of data difficult. For this reason, we hope that the present study will contribute to a better understanding of their evolution., (Copyright © 2020 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.)

In 2011, the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathology (SEAP) initiated a joint project to establish guidelines for biomarker testing in patients with advanced non-small-cell lung cancer based on the information available at the time. As this field is constantly evolving, these guidelines were updated in 2012 and 2015 and now in 2019. Current evidence suggests it should be mandatory to test all patients with this kind of advanced lung cancer for EGFR and BRAF mutations, ALK and ROS1 rearrangements and PD-L1 expression. The growing need to study other emerging biomarkers has promoted the routine use of massive sequencing (next-generation sequencing, NGS). However, the coordination of every professional involved and the prioritisation of the most suitable tests and technologies for each case remain a challenge., (Copyright © 2020 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.)

In 2011 the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathology (SEAP) started a joint project to establish guidelines on biomarker testing in patients with advanced non-small-cell lung cancer (NSCLC) based on current evidence. As this field is constantly evolving, these guidelines have been updated, previously in 2012 and 2015 and now in 2019. Current evidence suggests that the mandatory tests to conduct in all patients with advanced NSCLC are for EGFR and BRAF mutations, ALK and ROS1 rearrangements and PD-L1 expression. The growing need to study other emerging biomarkers has promoted the routine use of massive sequencing (next-generation sequencing, NGS). The coordination of every professional involved and the prioritisation of the most suitable tests and technologies for each case remains a challenge.

Purpose: Immunotherapy-based approaches are standard first-line treatments for advanced/metastatic lung cancer or for chemoradiotherapy consolidation in locally advanced disease. Uncertainty on how to treat patients at disease progression prompted us to develop a consensus document on post-immunotherapy options in Spain for patients with advanced wild-type lung adenocarcinoma., Methods: After extensive literature review, a 5-member scientific committee generated 33 statements in 4 domains: general aspects (n = 4); post-durvalumab in locally advanced disease (n = 6); post-first-line immunotherapy ± chemotherapy in advanced/metastatic disease (n = 11); and post-first-line platinum-based chemotherapy in advanced/metastatic disease (n = 12). A panel of 26 lung cancer experts completed 2 Delphi iterations through an online platform rating their degree of agreement/disagreement (first-round scale 1-5 and second-round scale 1-4, 1 = strongly disagree, 4/5 = strongly agree) for each statement. Second-round consensus: ≥ 70% of responses were in categories 1/2 (disagreement) or 3/4 (agreement)., Results: Consensus was reached for 2/33 statements in the first Delphi round and in 29/31 statements in the second round. Important variables informing treatment at disease progression with an immunotherapy-based treatment include: disease aggressiveness, previous treatment, accumulated toxicity, progression-free interval, PD-L1 expression, and tumour mutational burden. A platinum-based chemotherapy should follow a first-line immunotherapy treatment without chemotherapy. Treatment with docetaxel + nintedanib may be appropriate post-durvalumab in refractory patients or following progression to first-line chemotherapy + immunotherapy, or second-line chemotherapy after first-line immunotherapy, or first-line chemotherapy in some patients with low/negative PD-L1 expression, or second-line immunotherapy after first-line chemotherapy., Conclusions: To support decision making following progression to immunotherapy-based treatment in patients with advanced wild-type lung adenocarcinoma, a consensus document has been developed.

Purpose: To determine the current management of oral and intravenous chemotherapy (OC and IVC) in outpatient clinics of Oncology Departments in Spain to detect opportunities for improvement., Materials and Methods: The Spanish Society of Medical Oncology designed a questionnaire specifically for Heads of Oncology Department: 142 were invited and 52 responded., Results: In most centers, the waiting time (69.7%) and time at the outpatient clinic (84.8%) was shorter for patients receiving OC compared to those receiving IVC. The time spent at the outpatient clinic by the patients having OC was approximately 30 min (88.5%). In addition, the time expended by the oncologist with each patient was shorter when they were treated with OC in 21.2% of cases., Conclusions: Patients' waiting times and individual dedication of oncologists might be reduced by administering OC, and general management might be improved. This should be considered when planning therapies if OC is an option.

In 2011, the Spanish Society of Medical Oncology and the Spanish Society of Pathology started a joint project to establish recommendations on biomarker testing in patients with advanced non-small-cell lung cancer based on the current evidence. Most of these recommendations are still valid, but new evidence requires some aspects to be updated. Specifically, the recommendation about which biomarkers to test in which patients is being amended, and the best way to manage tumour samples and minimum requirements for biomarker test material are defined. Suitable techniques for testing for epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangement are also reviewed, and a consensus is reached on which situations warrant re-biopsy.

Purpose: The objective of the present study was to describe the prevalence and management of anaemia and iron deficiency (ID) in treatment-naïve patients with solid tumours in Spain and the incidence of anaemia over 4 months of cancer treatment in clinical practice., Methods: Multicentre, prospective and observational study in newly diagnosed cancer patients. Data on anaemia and iron parameters and its management were collected prior to the initiation of chemotherapy, at each cycle of chemotherapy and after 4 months of treatment. The main outcomes of the study were the prevalence of anaemia at baseline, its incidence during cancer treatment and the prevalence of absolute ID (AID) and functional ID (FID) prior to chemotherapy initiation., Results: A total of 295 patients were included in the study. Anaemia was present at diagnosis in 38.6 % of patients and was treated only in 32.5 % of those. A total of 106 patients (60.2 %) without anaemia at baseline developed anaemia during cancer treatment. Serum ferritin and transferrin saturation data were available for 151 of the patients (51.2 %) included in the study. The overall prevalence of ID was 59 %: 48 patients (31.8 %) presented with AID and 41 patients (27.2 %) presented with FID before starting anti-cancer therapy. Thirty-three of 44 non-anaemic iron-deficient patients did not receive any type of iron supplementation before initiating cancer therapy., Conclusions: Iron parameters are not commonly measured in newly diagnosed cancer patients. A correct evaluation and early management of ID could reduce the incidence of treatment-related anaemia in cancer patients.

Seventeen Middle Pleistocene crania from the Sima de los Huesos site (Atapuerca, Spain) are analyzed, including seven new specimens. This sample makes it possible to thoroughly characterize a Middle Pleistocene hominin paleodeme and to address hypotheses about the origin and evolution of the Neandertals. Using a variety of techniques, the hominin-bearing layer could be reassigned to a period around 430,000 years ago. The sample shows a consistent morphological pattern with derived Neandertal features present in the face and anterior vault, many of which are related to the masticatory apparatus. This suggests that facial modification was the first step in the evolution of the Neandertal lineage, pointing to a mosaic pattern of evolution, with different anatomical and functional modules evolving at different rates., (Copyright © 2014, American Association for the Advancement of Science.)

Lung cancer incidence is decreasing worldwide among men but rising among women due to recent changes in smoking patterns in both sexes. In Europe, the smoking epidemic has evolved different rates and times, and policy responses to it, vary substantially between countries. Differences in smoking prevalence are much more evident among European women reflecting the heterogeneity in cancer incidence rates. Other factors rather than smoking and linked to sex may increase women's susceptibility to lung cancer, such as genetic predisposition, exposure to sex hormones and molecular features, all of them linked to epidemiologic and clinical characteristics of lung cancer in women. However, biological bases of sex-specific differences are controversial and need further evaluation. This review focuses on the epidemiology and outcome concerning non-small cell lung cancer in women, with emphasis given to the Spanish population.

Neutropenia induced by chemotherapy (CT) is an infection risk factor associated to greater morbidity/mortality and dose-limiting toxicity that on many occasions requires a reduction of the dose of cytostatics or a delay in the administration of treatment. This may have a negative effect on the patient's quality of life and even diminish the efficacy of the treatment, especially when the intention is to cure or prolong survival. Management of treatment or prophylaxis of grade 3-4 neutropenia and febrile neutropenia with myeloid growth factors (CSF) varies very much in clinical practice, both in the time of starting treatment and the types of patients it is given to. The need to generalise and facilitate practice based on clinical evidence has led the Spanish Society of Medical Oncology (SEOM) to prepare clinical practice guidelines on the use of myeloid growth factors.

Patients with advanced non-small-cell lung cancer (NSCLC) carrying epidermal growth factor receptor (EGFR) mutations can now have specific treatment based on the result of biomarker analysis and patients with rearrangements of the anaplastic lymphoma kinase (ALK) gene will probably soon be able to. This will give them better quality of life and progression-free survival than conventional chemotherapy. This consensus statement was conceived as a joint initiative of the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathology (SEAP), and makes diagnostic and treatment recommendations for advanced NSCLC patients based on the scientific evidence on biomarker use. It therefore provides an opportunity to improve healthcare efficiency and resource use, which will undoubtedly benefit these patients. Although this field is in continuous evolution, at present, with the available data, this panel of experts recommends that all patients with advanced NSCLC of non-squamous cell subtype, or non-smokers regardless of the histological subtype, should be tested for EGFR gene mutations within a maximum of 7 days from the pathological diagnosis. Involved laboratories must participate in external quality control programmes. In contrast, ALK gene rearrangements should only be tested in the context of a clinical trial, although the promising data obtained will certainly justify in the near future its routine testing in patients with no EGFR mutations. Lastly, routine testing for other molecular abnormalities is not considered necessary in the current clinical practice.

The aim of this study is to describe the morphology of the roots and root canals of permanent lower second premolars (LP4s) with fully developed roots of five hominin groups: Homo sp. (ATE9-1 specimen) from Atapuerca-Sima del Elefante locality, H. antecessor (ATD6-4 and ATD6-125) from Atapuerca-Gran Dolina TD6 locality, H. heidelbergensis from Atapuerca-Sima de los Huesos locality, H. neanderthalensis from Krapina, Regourdou, and Abri Bourgeois-Delaunay localities, and two contemporary H. sapiens groups. The teeth were scanned by means of microtomography. The roots were divided into three virtual segments by three planes: cemento-enamel junction (CEJ), mid-root (MR), and mid-apex (MA). Volumetric and planar direct measurements of the whole teeth and each segment were taken. Descriptive statistical analyses and nonparametric Mann-Whiney test were performed to test for significant differences (P < 0.025) between groups. ATE9-1 and Gran Dolina-TD6 fossils present intricate radicular complexes that might be transitional between the morphologies of Australopithecus robustus and African early Homo and the derived conditions typically found in later Homo. In H. neanderthalensis and H. heidelbergensis, the root canals are wide, with small apical convergence. This trait is particularly pronounced in the Sima de los Huesos sample which may reflect a particularity of this population. Our study demonstrates the potential of hominin roots and root canals as untapped sources of taxonomic information when the tooth crown is fragmented. Future studies, including more fossil specimens and species will shed light in the polarity of the morphologies observed., (Copyright © 2012 Wiley Periodicals, Inc.)

The dispersal of hominins may have been favored by the opening of the landscape during the Early-Middle Pleistocene transition (EMP) in Western Europe. The structure of the small-vertebrate assemblages of the archaeo-paleontological karstic site of Gran Dolina in Atapuerca (Burgos, Spain) shows important environmental and climatic changes in the faunal succession, across the Matuyama-Brunhes boundary at 780 ka. These changes are interpreted to indicate impoverishment of the forests, along with an increase in dry meadows, and open lands in general that entailed a tendency towards the loss of diversity in small-vertebrate communities above the EMP. We evaluate variation in diversity of the faunal succession of Gran Dolina using Shannon's Second Theorem as an index of ecosystem structure. The long cultural-stratigraphic sequence of Gran Dolina during the EMP is somewhat similar in its completeness and continuity to that in the locality of Gesher Benot Ya'aqov in the Upper Jordan Valley. We also evaluate related data including faunal and floral (pollen) succession. Both localities present cold, dry and humid, warm fluctuations at the transition between the Early and the Middle Pleistocene. Comparisons between these sites present opportunities to understand large-scale climatic changes., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Paleomagnetic results obtained from the sedimentary fill at the Sima del Elefante site in Atapuerca, Spain, reveal a geomagnetic reversal, interpreted as the Matuyama-Brunhes boundary (0.78 Ma). The uppermost lithostratigraphic units (E17 through E19), which contain Mode II and III archaeological assemblages, display normal polarity magnetization, whereas the six lowermost units (E9 through E16) yield negative latitudinal virtual geomagnetic pole positions. Units E9 through E13, all of which display reverse magnetic polarity, contain Mode I (Oldowan) lithic tools, testifying to the presence of humans in the early Pleistocene (0.78-1.77 Ma).

We present a mandible recovered in 2003 from the Aurora Stratum of the TD6 level of the Gran Dolina site (Sierra de Atapuerca, northern Spain). The specimen, catalogued as ATD6-96, adds to the hominin sample recovered from this site in 1994-1996, and assigned to Homo antecessor. ATD6-96 is the left half of a gracile mandible belonging to a probably female adult individual with premolars and molars in place. This mandible shows a primitive structural pattern shared with all African and Asian Homo species. However, it is small and exhibits a remarkable gracility, a trait shared only with the Early and Middle Pleistocene Chinese hominins. Furthermore, none of the mandibular features considered apomorphic in the European Middle and Early Upper Pleistocene hominin lineage are present in ATD6-96. This evidence reinforces the taxonomic identity of H. antecessor and is consistent with the hypothesis of a close relationship between this species and Homo sapiens.

This study presents quantitative data on the rates of anterior tooth wear in a Pleistocene human population. The data were obtained for the hominin sample of the Sima de los Huesos site in Atapuerca, Spain. The fossil record belongs to a minimum of 28 individuals of the same biological population, assigned to the species Homo heidelbergensis. We have estimated the original and the preserved crown height of the mandibular incisors (I1 and I2) of 11 individuals, whose age at death can be ascertained from the mineralization stage and tooth eruption. Results provide a range of 0.276-0.348 and 0.288-0.360 mm per year for the mean wear rate of the mandibular I1 and I2, respectively, in individuals approximately 16-18 years old. These data suggest that incisors' crowns would be totally worn out toward the fifth decade of life. Thus, we expect the life expectancy of this population to be seriously limited. These data, which could be contrasted with results obtained on hominins at other sites, could be of interest for estimating the death age of adult individuals.

Systematic excavations, begun in 1987, at the Valdegoba cave site in northern Spain have yielded the remains of five individuals associated with a Middle Paleolithic stone tool technology and Pleistocene fauna. A fragmentary mandible of an adolescent (VB1), preserving nearly a full set of teeth, exhibits a symphyseal tubercle and slight incurvatio mandibulae anterior on the external symphysis. Both the superior and inferior transverse tori are present on the internal aspect. A second individual (VB2) is represented by a set of ten deciduous teeth consistent with an age at death of 6-9 months. A proximal manual phalanx (VB3) displays a relatively broad head, a characteristic which is found in both Neandertals, as well as European Middle Pleistocene hominids. VB4 is a fourth metatarsal that lacks the distal epiphysis, indicating it comes from an adolescent individual, and has a relatively high robusticity index. Finally, VB5 is a fifth metatarsal of an adult. The VB1 mandible shows a combination of archaic characteristics as well as more specific Neandertal morphological traits. The VB2 deciduous teeth are very small, and both the metrics and morphology seem more consistent with a modern human classification. The postcranial elements are undiagnostic, U-Th dating has provided an age of >350 ka for the base of the sequence and a date of <73.2+/-5 ka for level 7, near the top. Faunal analysis and radiometric dates from other nearby Mousterian sites suggests that the Valdegoba site is correlative with oxygen isotope stages 3-6 on the Iberian peninsula, and an Upper Pleistocene age for the Valdegoba hominids seems most reasonable., (Copyright 2001 Academic Press.)

The Middle Pleistocene Atapuerca-Sima de los Huesos (SH) site in Spain has yielded the largest sample of fossil hominids so far found from a single site and belonging to the same biological population. The SH dental sample includes a total of 452 permanent and deciduous teeth, representing a minimum of 27 individuals. We present a study of the dental size variation in these hominids, based on the analysis of the mandibular permanent dentition: lateral incisors, n=29; canines, n=27; third premolars, n=30; fourth premolars, n=34; first molars, n=38; second molars, n=38. We have obtained the buccolingual diameter and the crown area (measured on occlusal photographs) of these teeth, and used the bootstrap method to assess the amount of variation in the SH sample compared with the variation of a modern human sample from the Museu Antropologico of the Universidade of Coimbra (Portugal). The SH hominids have, in general terms, a dental size variation higher than that of the modern human sample. The analysis is especially conclusive for the canines. Furthermore, we have estimated the degree of sexual dimorphism of the SH sample by obtaining male and female dental subsamples by means of sexing the large sample of SH mandibular specimens. We obtained the index of sexual dimorphism (ISD=male mean/female mean) and the values were compared with those obtained from the sexed modern human sample from Coimbra, and with data found in the literature concerning several recent human populations. In all tooth classes the ISD of the SH hominids was higher than that of modern humans, but the differences were generally modest, except for the canines, thus suggesting that canine size sexual dimorphism in Homo heidelbergensis was probably greater than that of modern humans. Since the approach of sexing fossil specimens has some obvious limitations, these results should be assessed with caution. Additional data from SH and other European Middle Pleistocene sites would be necessary to test this hypothesis., (Copyright 2001 Academic Press.)

. We describe the pattern of dental development of Hominid XVIII from the Middle Pleistocene Sima de los Huesos (SH) site of the Sierra de Atapuerca (Burgos, Spain). As expected, this pattern is similar to that of modern humans. A delay of development of the lower and upper canines was observed. In contrast, the relative advanced development of the lower second molars and, especially, the upper and lower third molars is noteworthy. This latter feature seems to be common in Pleistocene hominids, and suggests that the pattern of dental development evolved in the genus Homo during the Pleistocene. In European Middle Pleistocene hominids, this pattern probably was facilitated by the extra space available in the mandible and maxilla for developing teeth., (Copyright 2001 Wiley-Liss, Inc.)

Parameters of a Middle Pleistocene human population such as the expected length of the female reproductive period (E(Y)), the expected interbirth interval (E(X)), the survival rate (tau) for females after the expected reproductive period, the rate (phi(2)) of women who, given that they reach first birth, do not survive to the end of the expected reproductive period, and the female infant plus juvenile mortality rate (phi(1)) have been assessed from a probabilistic standpoint provided that such a population were stationary. The hominid sample studied, the Sima de los Huesos (SH) cave site, Sierra de Atapuerca (Spain), is the most exhaustive human fossil sample currently available. Results suggest that the Atapuerca (SH) sample can derive from a stationary population. Further, in the case that the expected reproductive period ends between 37 and 40 yr of age, then 24 less, similarE(Y) less, similar27 yr, E(X)=3 yr, 0.224

Metric and shape features of the Lower Pleistocene mandibular specimen ATD605 from the level 6 of Gran Dolina site (Atapuerca, Spain) are compared with a large sample of fossil hominid mandibles. The analysis shows that ATD6-5 displays a generalized morphology largely shared with both African and European Lower and Middle Pleistocene samples. However, distinctive African traits, such as corpus robustness and strong alveolar prominence, are absent in the Gran Dolina specimen. At the same time, none of the apomorphic features that characterize Middle and early Upper Pleistocene European hominids can be recognized in ATD6-5. Finally, the Gran Dolina specimen displays a remarkable position of the mylohyoid groove, only comparable to that found in immature specimens of Homo ergaster, and very rarely in adult H. sapiens. The morphology of ATD6-5 supports the hypothesis of an African origin for the first Europeans with subsequent phylogenetic continuity with Middle Pleistocene populations in Europe. These findings are consistent with H. antecessor being the last common ancestor of Neandertals and H. sapiens., (Copyright 1999 Academic Press.)

Gran Dolina is part of an archaeological and paleontological complex located in the Sierra de Atapuerca karstic system (Burgos, Spain). The Trinchera del Ferrocarril sites were discovered as a consequence of the construction of a railway for the transport of minerals at the end of the nineteenth century. The systematic excavation of the upper Gran Dolina levels was initiated in 1981. In 1993, a 6 m(2)biostratigraphic survey pit was started, reaching level TD6 in 1994. This level was excavated during four consecutive years, yielding human fossils, identified as Homo antecessor, in association with lithic and faunal remains, dating to more than 0.78 m.y.a., (Copyright 1999 Academic Press.)

Hominid remains found in 1994 from the stratified Gran Dolina karst-filling at the Atapuerca site in NE Spain were dated to somewhat greater than 780 ka based on palaeomagnetic measurements, making these the oldest known hominids in Europe (sensu stricto). We report new ESR and U-series results on teeth from four levels of the Gran Dolina deposit which confirm the palaeomagnetic evidence, and indicate that TD6 (from which the human remains have been recovered) dates to the end of the Early Pleistocene. The results for the other levels are consistent with estimates based mainly on microfaunal evidence, and suggest that TD8, TD10 and TD11 date to the Middle Pleistocene., (Copyright 1999 Academic Press.)

A descriptive and comparative study of the human dental remains recovered from level six (Aurora stratum) of the Gran Dolina (TD) site, Sierra de Atapuerca, northern Spain, is presented. The TD6 dental sample consists of two deciduous and 28 permanent teeth, belonging to a minimum of six individuals. Paleomagnetic analyses of the TD sequence suggest an age for the Aurora stratum of greater than 780 ka. The associated fossil macro- and micrommals are consistent with a date for the Atapuerca-TD6 hominids at the end of the Early Pleistocene. As a whole, the size of the TD6 teeth is large and comparable to that of the African Lower Pleistocene hominids. Most morphological dental traits are plesiomorphic for the genus Homo, whereas the shape analysis has revealed some size-related trends that differ from those seen in early Homo. Thus, the relative size increase of the maxillary and mandibular anterior teeth and buccolingual diameter of the first molars, the reduction of the third molars and lower canines, and the P(3)>P(4)size sequence are all characteristic of the population represented by the TD6 hominids. The morphological evidence suggests that the TD6 hominids are closer to African Lower and early Middle Pleistocene hominids than they are to European Middle Pleistocene hominids. However, some dental traits of the TD6 hominids, such as the expansion of the anterior teeth, the P(3)>P(4)size sequence, and the morphology of the lower canine also suggest an evolutionary continuity between the population represented by these hominids and the European Middle Pleistocene population. Furthermore, dental evidence indicates that the TD6 hominids are clearly distinct from Asian H. erectus. Dental evidence also suggests that the TD6 hominids could represent an evolutionary connection between H. ergaster and H. heidelbergensis., (Copyright 1999 Academic Press.)

The study of the faunal and lithic assemblage (including almost a hundred human fossil remains) recovered from the Aurora stratum-TD6 level of the Lower Pleistocene cave site of Gran Dolina (Sierra de Atapuerca, Spain) has allowed us to answer some important questions concerning the debate about the earliest evidence for human occupation of Europe. However, it has also started new discussions about some geographical, ecological, and economic aspects of this earliest occupation. The nature (definitive or ephemeral) of the first occupation, as well as the model for the arrival of the Acheulean (Mode 2) in Europe are also issues for discussion., (Copyright 1999 Academic Press.)

The Middle Pleistocene site of Sima de los Huesos in Sierra de Atapuerca, Spain, has yielded around 2,500 fossils from at least 33 different hominid individuals. These have been dated at more than 200,000 years ago and have been classified as ancestors of Neanderthals. An almost complete human male pelvis (labelled Pelvis 1) has been found, which we associate with two fragmentary femora. Pelvis 1 is robust and very broad with a very long superior pubic ramus, marked iliac flare, and a long femoral neck. This pattern is probably the primitive condition from which modern humans departed. A modern human newborn would pass through the birth canal of Pelvis 1 and this would be even larger in a female individual. We estimate the body mass of this individual at 95 kg or more. Using the cranial capacities of three specimens from Sima de los Huesos, the encephalization quotients are substantially smaller than in Neanderthals and modern humans.

Casts of nonocclusal enamel surfaces of 190 teeth from the Middle Pleistocene site of Sima de los Huesos have been micrographed by scanning electron microscopy. Microscopic analyses of striation density and length by orientation show distinct patterns of intrapopulation variability. Significant differences in the number and length of the striations by orientation are found between maxillary and mandibular teeth. This probably reflects differences in the mechanical forces involved in the process of chewing food. Significant differences are present between isolated and in situ teeth that could be caused by postdepositional processes differentially affecting the isolated teeth. In addition, a distinct and very unusual striation pattern is observed in a sample of teeth that can be explained only by a strong nondietary, most probably postmortem abrasion of the enamel surfaces. These teeth have a very high density of scratches, shorter in length than those found on other teeth, that are not indicative of dietary habits. No known depositional process may account for the presence of such postmortem wear since heavy transportation of materials within the clayish sediments has been discarded for the site. Despite this, a characteristic dietary striation pattern can be observed in most of the teeth analyzed. Most likely the diet of the Homo heidelbergensis hominids from Sima de los Huesos was highly abrasive, probably with a large dependence on hard, poorly processed plant foods, such as roots, stems, and seeds. A highly significant sex-related difference in the striation pattern can also be observed in the teeth analyzed, suggesting a differential consistency in the foods eaten by females and males.

The study of life history evolution in hominids is crucial for the discernment of when and why humans have acquired our unique maturational pattern. Because the development of dentition is critically integrated into the life cycle in mammals, the determination of the time and pattern of dental development represents an appropriate method to infer changes in life history variables that occurred during hominid evolution. Here we present evidence derived from Lower Pleistocene human fossil remains recovered from the TD6 level (Aurora stratum) of the Gran Dolina site in the Sierra de Atapuerca, northern Spain. These hominids present a pattern of development similar to that of Homo sapiens, although some aspects (e.g., delayed M3 calcification) are not as derived as that of European populations and people of European origin. This evidence, taken together with the present knowledge of cranial capacity of these and other late Early Pleistocene hominids, supports the view that as early as 0.8 Ma at least one Homo species shared with modern humans a prolonged pattern of maturation.

Background: The prevalence of tobacco consumption in scholars has been determined by self-governed inquiries, methodology that presents limitations of reliability and validity. This obstacle has been endeavoured to overcome through methodological inspections such as the test-retest valuation. On the contrary, the available analytical methods (i.e., determination of cotinine in urine or determination of carbon monoxide [CO] in exhaled air) have not been used up to now in this type of studies. Their use together with the inquiries could complement the results of the questionnaires and verify their reliability., Population and Methods: 814 scholars took part in the survey, being valid the results of 809, 385 male students and 424 female students, 13 to 24 years old (mean 15.90, SD 1.73) from an urban high school and another in the rural area. The survey included a survey and the measurement of CO levels in exhaled air in the same scholar centre., Results: 257 scholars stated that they had never tried tobacco and in 15 of them (5.8%) levels of CO were equal or higher than 10 ppm (14.26, SD 4.35 ppm). 589 students stated that were not regular smokers; in 46 of them (7.8%) levels of CO were superior to 10 ppm (13.87, SD 4.68). The morning when the survey was held 629 students assured that they had not smoked: in 52 of them (8.3%) levels of CO higher than 10 ppm were observed. The mean level of CO observed in these students was 13.5 (SD 4.4) ppm. In our survey, the measurement of CO in exhaled air allowed us to show percentage between 5.8 and 8.3% of students whose answers to the different questions were not reliable., Conclusions: The reliability of the results, observed through the carrying out of surveys, can be determined with the use of analytical methods that, owe to their simplicity, can be used massively. We have not found any relation between the shortage of reliability and the variants studied (age, sex or habitat), which reaffirms the difficulty in identifying variants that can determine those "deceives" and demands for its identification the need of practicing analytical determinations.

Castilla y León is a rural region with a very sparse population of about 2,560,000 habitants. Special health care challenges appear due to this region's very aged population and large dimensions. A theoretical model of services of Telemedicine is proposed and an experimental teleradiology trial is carried out between a rural Health Care Centre and its Reference Hospital to make easier the planning of future projects. The total number of studies was increased due to availability of specialised support and higher skills of physicians, but the percentage of studies consulted to specialists diminished. Continuing education through physicians communication was highly improved.

Studies carried out in the past ten years have found the prevalence or smoking among children and adolescents to be high, with the greatest increase observed for girls and young women, indicating increasing gender-related differences. The aim of our study was to determine the prevalences and differences among children and adolescents of both sexes with regard to experimentation and use of tobacco products and to determine any possible influence related to urban or rural environment. Eight hundred fourteen students participated, with 809 providing valid data for study: 385 males and 424 females ranging in age from 13 to 24 years old (15.90 +/- 1.73 years). The subjects studied in either an urban or a rural school. Data was collected on campus by questionnaire and carbon monoxide in expired air was measured. Smoking had been tried by 68.2%: 241 males (62.5%) and 31 females (73.3%) (p < 0.001). Habitual smoking was reported by 27.2%: 78 males (20.2%) and 142 females (33.4%) (p < 0.001). Mean ages of experimenters (16.18 +/- 1.78 years) and smokers (16.55 +/- 1.85 years) were higher than the mean age of non-experimenters (15.29 +/- 1.43) (p < 0.001). Habitual smokers consumed a mean 2.71 +/- 1.68 cigarettes/day and consumption was similar for both sexes. CO in expired air was 12.61 +/- 6.39 ppm in these smokers, significantly higher (p < 0.001) than that found in experimenters and non smokers (p 0.001). One hundred eighty students (22.2%), 119 females and 61 males (p < 0.001), reported having smoked on the morning of the study. In total, 81.8% of the students who described themselves as smokers had smoked that morning: 78.2% of the males and 83.9% of the females. CO in this group was 13.95 +/- 1.69 ppm, significantly higher than that found for the other groups (non smokers or experimenters). We found no significant differences between number of cigarettes/day smoked by students who reported being habitual smokers and the number consumed the morning of data collection by students who had smoked the day of the study. Changes can be observed in patterns of tobacco use among children and young people. We found that nearly all aspects related to experimentation and consumption of tobacco are significantly higher in females.

It has been suggested that European Middle Pleistocene humans, Neandertals, and prehistoric modern humans had a greater sexual dimorphism than modern humans. Analysis of body size variation and cranial capacity variation in the large sample from the Sima de los Huesos site in Spain showed instead that the sexual dimorphism is comparable in Middle Pleistocene and modern populations.

We report here on the palaeodemographic analysis of the hominid sample recovered to date from the Sima de los Huesos (SH) Middle Pleistocene cave site in the Sierra de Atapuerca (Burgos, Spain). The analysis of the mandibular, maxillary, and dental remains has made it possible to estimate that a minimum of 32 individuals, who probably belonged to the same biological population, are represented in the current SH human hypodigm. The remains of nine-individuals are assigned to males, and nine to females, suggesting that a 1:1 sex ratio characterizes this hominid sample. The survivorship curve shows a low representation of infants and children, a high mortality among the adolescents and prime-age adults, and a low older adult mortality. Longevity was probably no greater than 40 years. This mortality pattern (adolescents and adults); which in some aspects resembles that observed in Neandertals, is quite different from those reported for recent foraging human groups. The adult age-at-death distribution of the SH hominid sample appears to be neither the consequence of underaging the older adults, nor of differential preservation or of the recognition of skeletal remains. Thus if we accept that they had a life history pattern similar to that of modern humans there would appear to be a clear contradiction between the demographic distribution and the demographic viability of the population represented by the SH hominid fossils. The possible representational bias of the SH hominid sample, as well as some aspects of the reproductive biology of the Pleistocene populations are also discussed.

Human fossil remains recovered from the TD6 level (Aurora stratum) of the lower Pleistocene cave site of Gran Dolina, Sierra de Atapuerca, Spain, exhibit a unique combination of cranial, mandibular, and dental traits and are suggested as a new species of Homo-H. antecessor sp. nov. The fully modern midfacial morphology of the fossils antedates other evidence of this feature by about 650, 000 years. The midfacial and subnasal morphology of modern humans may be a retention of a juvenile pattern that was not yet present in H. ergaster. Homo antecessor may represent the last common ancestor for Neandertals and modern humans.

The dental sample recovered from the Sima de los Huesos (SH) Middle Pleistocene cave site of the Sierra de Atapuerca (Spain) includes 296 specimens. Interproximal wear grooves have been observed in 20 maxillary and mandibular posterior teeth belonging to at least five of the 32 individuals identified so far in the SH hypodigm. Interproximal grooving affected only the adults, and at an age between 25 and 40 years. The appearance, morphology, and location pattern of the SH wear grooves are similar to those reported in other fossil hominids and in more recent human populations. Two alternative proposals, the toothpicking and the fiber or sinew processing hypotheses, compete for explaining the formation of this anomalous wear. The characteristics observed in the wear grooves of the SH teeth are compatible only with the habitual probing of interdental spaces by means of hard and inflexible objects. Dietary grit may also have contributed to the abrasion of the root walls during the motion of the dental probes.

Human remains dating to more than 780,000 years ago are associated with a rich faunal and lithic assemblage in the Pleistocene cave site of Gran Dolina (TD), Sierra de Atapuerca, Burgos, Spain. The micromammal species represent the late Biharian (Mimomys savini zone), and the lithic objects represent pre-Acheulean technology (Mode 1) and comes from the TD6 level below the Matuyama-Brunhes boundary. The Gran Dolina hominid fossils cannot be comfortably accommodated in any of the defined Homo species. They could be considered a primitive form of Homo heidelbergensis, but a new species might be named in the future if the sample is enlarged. The new human fossil evidence demonstrates that Western Europe was settled at least since the late early Pleistocene.

In order to reassess previous hypotheses concerning dental size reduction of the posterior teeth during Pleistocene human evolution, current fossil dental evidence is examined. This evidence includes the large sample of hominid teeth found in recent excavations (1984-1993) in the Sima de los Huesos Middle Pleistocene cave site of the Sierra de Atapuerca (Burgos, Spain). The lower fourth premolars and molars of the Atapuerca hominids, probably older than 300 Kyr, have dimensions similar to those of modern humans. Further, these hominids share the derived state of other features of the posterior teeth with modern humans, such as a similar relative molar size and frequent absence of the hypoconulid, thus suggesting a possible case of parallelism. We believe that dietary changes allowed size reduction of the posterior teeth during the Middle Pleistocene, and the present evidence suggests that the selective pressures that operated on the size variability of these teeth were less restrictive than what is assumed by previous models of dental reduction. Thus, the causal relationship between tooth size decrease and changes in food-preparation techniques during the Pleistocene should be reconsidered. Moreover, the present evidence indicates that the differential reduction of the molars cannot be explained in terms of restriction of available growth space. The molar crown area measurements of a modern human sample were also investigated. The results of this study, as well as previous similar analyses, suggest that a decrease of the rate of cell proliferation, which affected the later-forming crown regions to a greater extent, may be the biological process responsible for the general and differential dental size reduction that occurred during human evolution.

The prevalence and chronology of enamel hypoplasias were studied in a hominid dental sample from the Sima de los Huesos (SH) Middle Pleistocene site at the Sierra de Atapuerca (Burgos, northern Spain). A total of 89 permanent maxillary teeth, 143 permanent mandibular teeth, and one deciduous lower canine, belonging to a minimum of 29 individuals, were examined. Excluding the antimeres (16 maxillary and 37 mandibular cases) from the sample, the prevalence of hypoplasias in the permanent dentition is 12.8% (23/179), whereas the deciduous tooth also showed an enamel defect. No statistically significant differences were found between both arcades and between the anterior and postcanine teeth for the prevalence of hypoplasias. In both the maxilla and the mandible the highest frequency of enamel hypoplasias was recorded in the canines. Only one tooth (a permanent upper canine) showed two different enamel defects, and most of the hypoplasias were expressed as faint linear horizontal defects. Taking into account the limitations that the incompleteness of virtually all permanent dentitions imposes, we have estimated that the frequency by individual in the SH hominid sample was not greater than 40%. Most of the hypoplasias occurred between birth and 7 years (N = 18, X = 3.5, SD = 1.3). Both the prevalence and severity of the hypoplasias of the SH hominid sample are significantly less than those of a large Neandertal sample. Furthermore, prehistoric hunter-gatherers and historic agricultural and industrial populations exhibit a prevalence of hypoplasias generally higher than that of the SH hominids. Implications for the survival strategies and life quality of the SH hominids are also discussed.