Late Pleistocene Neanderthal exploitation of stable and mosaic ecosystems in northern Iberia shown by multi-isotope evidence

The carbon, nitrogen and sulphur stable isotope analyses and the stable isotope analyses of bioapatite carbonates were funded as part of the ABRUPT project (HAR2017-84997-P) funded by the Ministry of Science, Innovation and Universities and the SUBSILIENCE project funded by the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement no. 818299—ERC-2018-Consolidator), both awarded to ABM-A. SP was supported by the Max Planck Society and the University of Aberdeen during the time of this project, and the oxygen isotope analysis of bioapatite phosphates was funded by the Max Planck Society. Access to the archaeological collections was granted by the Museo de Arqueología de Bizkaia (Basque Government), and initial sampling for carbon and nitrogen isotope analysis was achieved by Hazel Reade funded by the FP7-PEOPLE-2012-CIG- 322112 project) and ABM-A. We appreciate Joseba Rios-Garaizar's advice about Axlor stratigraphy during the sampling process. We thank Ignacio Valera (IBBTEC, University of Cantabria) for kindly allowing the use of his laboratory facilities for collagen extraction. We thank Carlos Revilla Gómez (IBBTEC, University of Cantabria) for laboratory assistance during collagen extraction. Thanks are also due to Manuel Trost (MPI-EVA) for assistance during silver phosphate preparation and to Sven Steinbrenner for assistance with TC/EA-IRMS. KB is supported by a Philip Leverhulme Prize from the Leverhulme Trust (PLP-2019-284).Peer reviewedPublisher PD

Hospital-based Surveillance Provides Insights Into the Etiology of Pediatric Bacterial Meningitis in Yaoundé, Cameroon, in the Post-Vaccine Era.

BACKGROUND:Meningitis is endemic to regions of Cameroon outside the meningitis belt including the capital city, Yaoundé. Through surveillance, we studied the etiology and molecular epidemiology of pediatric bacterial meningitis in Yaoundé from 2010 to 2016. METHODS:Lumbar puncture was performed on 5958 suspected meningitis cases; 765 specimens were further tested by culture, latex agglutination, and/or polymerase chain reaction (PCR). Serotyping/grouping, antimicrobial susceptibility testing, and/or whole genome sequencing were performed where applicable. RESULTS:The leading pathogens detected among the 126 confirmed cases were Streptococcus pneumoniae (93 [73.8%]), Haemophilus influenzae (18 [14.3%]), and Neisseria meningitidis (15 [11.9%]). We identified more vaccine serotypes (19 [61%]) than nonvaccine serotypes (12 [39%]); however, in the latter years non-pneumococcal conjugate vaccine serotypes were more common. Whole genome data on 29 S. pneumoniae isolates identified related strains (<30 single-nucleotide polymorphism difference). All but 1 of the genomes harbored a resistance genotype to at least 1 antibiotic, and vaccine serotypes harbored more resistance genes than nonvaccine serotypes (P < .05). Of 9 cases of H. influenzae, 8 were type b (Hib) and 1 was type f. However, the cases of Hib were either in unvaccinated individuals or children who had not yet received all 3 doses. We were unable to serogroup the N. meningitidis cases by PCR. CONCLUSIONS:Streptococcus pneumoniae remains a leading cause of pediatric bacterial meningitis, and nonvaccine serotypes may play a bigger role in disease etiology in the postvaccine era. There is evidence of Hib disease among children in Cameroon, which warrants further investigation

Clinical Relevance of Tumor Cells with Stem-Like Properties in Pediatric Brain Tumors

BACKGROUND: Primitive brain tumors are the leading cause of cancer-related death in children. Tumor cells with stem-like properties (TSCs), thought to account for tumorigenesis and therapeutic resistance, have been isolated from high-grade gliomas in adults. Whether TSCs are a common component of pediatric brain tumors and are of clinical relevance remains to be determined. METHODOLOGY/PRINCIPAL FINDINGS: Tumor cells with self-renewal properties were isolated with cell biology techniques from a majority of 55 pediatric brain tumors samples, regardless of their histopathologies and grades of malignancy (57% of embryonal tumors, 57% of low-grade gliomas and neuro-glial tumors, 70% of ependymomas, 91% of high-grade gliomas). Most high-grade glioma-derived oncospheres (10/12) sustained long-term self-renewal akin to neural stem cells (>7 self-renewals), whereas cells with limited renewing abilities akin to neural progenitors dominated in all other tumors. Regardless of tumor entities, the young age group was associated with self-renewal properties akin to neural stem cells (P = 0.05, chi-square test). Survival analysis of the cohort showed an association between isolation of cells with long-term self-renewal abilities and a higher patient mortality rate (P = 0.013, log-rank test). Sampling of low- and high-grade glioma cultures showed that self-renewing cells forming oncospheres shared a molecular profile comprising embryonic and neural stem cell markers. Further characterization performed on subsets of high-grade gliomas and one low-grade glioma culture showed combination of this profile with mesenchymal markers, the radio-chemoresistance of the cells and the formation of aggressive tumors after intracerebral grafting. CONCLUSIONS/SIGNIFICANCE: In brain tumors affecting adult patients, TSCs have been isolated only from high-grade gliomas. In contrast, our data show that tumor cells with stem cell-like or progenitor-like properties can be isolated from a wide range of histological sub-types and grades of pediatric brain tumors. They suggest that cellular mechanisms fueling tumor development differ between adult and pediatric brain tumors

Research in the Bioarchaeology Laboratory in the International Institute for Prehistoric Research (IIIPC) - University of Cantabria

RESUMEN: Cantabria se caracteriza por ser una región especialmente rica en yacimientos de época prehistórica. En ellos, se han podido recuperar múltiples evidencias que, con la aplicación de las técnicas metodológicas adecuadas, permiten reconstruir los modos de vida de los grupos humanos del pasado, la explotación que realizaban del medio, su tipo de dieta, su movilidad, así como el tipo de clima y medioambiente en que habitaron, entre otros aspectos. Una de las líneas de investigación más novedosas desarrollada en la región es la Bioarqueología, entendida como el estudio y análisis de restos biológicos procedentes de yacimientos arqueológicos. En este artículo se muestran las diferentes colecciones de referencia de materiales bioarqueológicos que alberga el Laboratorio de Bioarqueología del Instituto Internacional de Investigaciones Prehistóricas de Cantabria (Universidad de Cantabria), así como las investigaciones desarrolladas en dicha institución sobre esta temática en los últimos años.ABSTRACT: Cantabria is a region characterised as especially rich in prehistoric archaeological sites. These sites can be investigated using stateof- the art methodologies, making it possible to reconstruct the way of life of humans in the past, answering questions about diet and mobility, and what the climate and environment was like, amongst other things. One of these newly-developed lines of research in the region is bioarchaeology, which is the study and analysis of biological remains recovered from archaeological sites. This article introduces the different bioarchaeological reference collection materials housed in the Bioarchaeology Laboratory at the International Institute of Prehistoric Research in Cantabria (University of Cantabria), as well as the bioarchaeological research that has been carried out within the institution in the last few years.La investigación llevada a cabo por el grupo de investigadores del Laboratorio de Bioarqueología ha sido posible gracias a diversas fuentes de financiación españolas y europeas. En primer lugar, a título personal señalar las siguientes ayudas: Programa Ramon y Cajal a ABMA (RYC-2011-00695), Programa Juan de la Cierva a IGZ (JCI-2012-12094) y DCS (IJCI- 2014-20590), Marie Skłodowska-Curie Individual Fellowship a JJ (H2020-MSCA-IF-2014-Ref. 656122), Becas Predoctorales FPI a JMG (BES-2013-063309) y RSR (BES-2014-070075), AH (BES-2015-075176), Predoctorales UC a ILD y AGE y Técnicos de Apoyo I+D a LAP (PTA2013-8401-I). En segundo lugar, parte de estas investigaciones forma o ha formado parte de los siguientes proyectos de investigación financiados por la Comisión Europea (FP7-PEOPLE- 2012-CIG (322112), la British Academy y The Royal Society (Newton International Fellowship NF100413), y el Ministerio de Economía y Competitividad de España (HAR2008-06477-C03-00/HIST; HAR2010- 22115-C02-01; HAR2011-29907-C03-00; HAR2012- 33956; HAR2013-46802-P; HAR2014-51830-P). Por último, queremos agradecer el acceso a los fondos de museos como los depositados en el Museo de Prehistoria y Arqueología de Cantabria (MUPAC), el Museo de Altamira, Centro de Patrimonio Cultural Mueble de Gipuzkoa (Gordailua), Museo Arqueológico de Asturias, Grupo de Ingeniería Fotónica de la Universidad de Cantabria, Laboratorio de la División de Ciencia e Ingeniería de los Materiales de la Universidad de Cantabria (LADICIM) e Instituto de Biomedicina y Biotecnología de Cantabria

Challenge of conducting a placebo-controlled randomized efficacy study for influenza vaccine in a season with low attack rate and a mismatched vaccine B strain: a concrete example

<p>Abstract</p> <p>Background</p> <p>Our aim was to determine the efficacy of a trivalent inactivated split virus influenza vaccine (TIV) against culture-confirmed influenza A and/or B in adults 18 to 64 years of age during the 2005/2006 season in the Czech Republic.</p> <p>Methods</p> <p>6203 subjects were randomized to receive TIV (N = 4137) or placebo (N = 2066). The sample size was based on an assumed attack rate of 4% which provided 90% power to reject the hypothesis that vaccine efficacy (VE) was ≥ 45%. Cases of influenza like illness (defined as fever (oral temperature ≥37.8°C) plus cough and/or sore throat) were identified both by active (biweekly phone contact) and passive (self reporting) surveillance and nasal and throat swabs were collected from subjects for viral culture.</p> <p>Results</p> <p>TIV was well tolerated and induced a good immune response. The 2005/2006 influenza season was exceptionally mild in the study area, as it was throughout Europe, and only 46 culture-confirmed cases were found in the study cohort (10 influenza A and 36 influenza B). Furthermore among the B isolates, 35 were identified as B/Hong Kong 330/2001-like (B/Victoria/2/87 lineage) which is antigenically unrelated to the vaccine B strain (B/Yamagata/16/88 lineage). The attack rate in the vaccine group (0.7%) was not statistically significantly different from the attack rate in the placebo group (0.9%).</p> <p>Conclusion</p> <p>Due to the atypical nature of the influenza season during this study we were unable to assess TIV efficacy. This experience illustrates the challenge of conducting a prospective influenza vaccine efficacy trial during a single season when influenza attack rates and drift in circulating strains or B virus lineage match can be difficult to estimate in advance.</p> <p>Trial Registration</p> <p>Clinical trial registery: NCT00197223.</p

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead