La tumba hipogea de Bolores (Torres Vedras): una aproximación interdisciplinar a la comprensión del paisaje social del Neolítico Final/Edad del Cobre de la Península Ibérica

To better understand the sociopolitical landscape of the Portuguese Estremadura during the Late Neolithic/Copper Age, interdisciplinary excavations were conducted at Bolores (Torres Vedras), in the Sizandro River Valley. Following a test season in 1986, a University of Iowa team conducted four campaigns between 2007 and 2012. Bolores is a rock-cut tomb used primarily between 2800-2600 cal BC for the burial of adults, adolescents, and children (MNI=36). The architectural, material cultural, and bioarchaeological evidence suggests that Bolores housed the remains of a distinctive group of local individuals who marked their difference from other burial populations in the Sizandro and Estremadura through material culture and tomb architecture. Social differences were denoted spatially and through offerings of material goods. No social stratification is evident, however, that would suggest a state-level society: there are no wealthy child burials and no significant health or dietary disparities within this population or between it and others in the region.Para comprender mejor el paisaje sociopolítico de la Extremadura portuguesa durante el Neolítico Final/Edad del Cobre se han llevado a cabo excavaciones interdisciplinares en Bolores (Torres Vedras), en el valle del río Sizandro. Tras una campaña de prueba en 1986, un equipo de la Universidad de Iowa realizó cuatro campañas entre 2007 y 2012. Bolores es una tumba hipogea que fue utilizada principalmente entre 2800 y 2600 cal BCE como enterramiento colectivo para adultos, adolescentes y niños (NMI=36). Los datos arquitectónicos, bioarqueológicos y de cultura material analizados hasta la fecha sugieren que Bolores albergó los restos de un grupo social distintivo compuesto de individuos locales que marcaban sus diferencias con otras poblaciones funerarias del Sizandro y Extremadura portuguesa mediante la cultura material y la arquitectura funeraria. Las diferencias sociales en la población de Bolores fueron señaladas espacialmente y marcadas mediante las ofrendas de bienes materiales. Sin embargo, no se aprecia una estratificación social significativa que sugiera una sociedad de nivel estatal: no hay enterramientos infantiles ricos, ni disparidades en la salud o dieta de esta población funeraria o entre esta población y otras en la región de Torres Vedras

Explore Transplant at Home: A randomized control trial of an educational intervention to increase transplant knowledge for Black and White socioeconomically disadvantaged dialysis patients

BackgroundCompared to others, dialysis patients who are socioeconomically disadvantaged or Black are less likely to receive education about deceased donor kidney transplant (DDKT) and living donor kidney transplant (LDKT) before they reach transplant centers, often due to limited availability of transplant education within dialysis centers. Since these patients are often less knowledgeable or ready to pursue transplant, educational content must be simplified, made culturally sensitive, and presented gradually across multiple sessions to increase learning and honor where they are in their decision-making about transplant. The Explore Transplant at Home (ETH) program was developed to help patients learn more about DDKT and LDKT at home, with and without telephone conversations with an educator.Methods and study designIn this randomized controlled trial (RCT), 540 low-income Black and White dialysis patients with household incomes at or below 250 % of the federal poverty line, some of whom receive financial assistance from the Missouri Kidney Program, will be randomly assigned to one of three education conditions: (1) standard-of-care transplant education provided by the dialysis center, (2) patient-guided ETH (ETH-PG), and (3) health educator-guided ETH (ETH-EG). Patients in the standard-of-care condition will only receive education provided in their dialysis centers. Those in the two ETH conditions will receive four video and print modules delivered over an 8 month period by mail, with the option of receiving supplementary text messages weekly. In addition, patients in the ETH-EG condition will participate in multiple telephonic educational sessions with a health educator. Changes in transplant knowledge, decisional balance, self-efficacy, and informed decision making will be captured with surveys administered before and after the ETH education.DiscussionAt the conclusion of this RCT, we will have determined whether an education program administered to socioeconomically disadvantaged dialysis patients, over several months directly in their homes, can help more individuals learn about the options of DDKT and LDKT. We also will be able to examine the efficacy of different educational delivery approaches to further understand whether the addition of a telephone educator is necessary for increasing transplant knowledge.Trial registrationClinicalTrials.gov, NCT02268682

Zirconium-catalyzed alkene hydrophosphination and dehydrocoupling with an air-stable, fluorescent primary phosphine

Zirconium-catalyzed alkene hydrophosphination and dehydrocoupling with an air-stable, fluorescent primary phosphine 8-[(4-phosphino)phenyl]-4,4-dimethyl-1,3,5,7-tetramethyl-2,6-diethyl- 4-bora-3a,4a-diaza-s-indacene furnishes fluorescent phosphine products. Hydrophosphination of the fluorescent phosphine produces products with a complete selectivity for the secondary product. A key intermediate in catalysis, a zirconium phosphido compound, was isolated

A mid-third millennium BC collective burial cave in central Iberia: El Rebollosillo (Torrelaguna, Madrid)

El Rebollosillo es una pequeña cueva kárstica situada en el centro de la Península Ibérica utilizada para la disposición de enterramientos secundarios en la mitad del III milenio AC. Presentamos resultados bioantropológicos, isotópicos (87Sr/86Sr, δ13C y δ18O) y 16 dataciones radiocarbónicas de los restos humanos, una descripción cuantificada de los 43 fragmentos cerámicos y de caracterización mineralógica de 6 cuentas recuperadas durante la excavación de 1989, cuatro de las cuales probablemente proceden de Palazuelo de las Cuevas (Zamora). El análisis bioantropológico indica un mínimo de 21 individuos con todos los rangos de edad y sexo. Se han detectado bajos porcentajes de patologías, mayoritariamente cálculo dental y caries, con casos puntuales de cribra orbitalia, periostosis y artrosis. La disposición de los restos sugiere que sólo los adultos recibieron un tratamiento claramente individualizado, quizás acorde con un estatus adquirido con la edad. Proponemos que el registro representa la última fase de un programa mortuorio cuyas etapas previas debieron desarrollarse en otros lugares y valoramos estos resultados en el contexto del registro funerario regional.El Rebollosillo is a small karstic cave located in the center of Iberia used for the disposition of secondary burials during the mid third millennium BC. We present bioanthropological, isotopic (87Sr/86Sr, δ 13C y δ 18O) analyses and 16 radiocarbon dates on human remains, as well as mineralogical characterization of 6 beads (4 of them variscite from Palazuelo de las Cuevas, Zamora), and a quantitative analysis of 43 pottery fragments recovered during the 1989 excavations. A minimum of 21 individu-als have been identified, covering all age ranges and sex. Low percentages of pathologies have been detected, mainly dental calculus and caries, with specific cases of cribra orbitalia, periostosis and arthritis. Only adults received a clearly individualized treatment, suggestive of achieved status. We interpret the evidence as a multi-staged mortuary program, the last phase of which is documented at the site, with previous stages perhaps carried out elsewhere, and we evaluate these results in the context of the regional funerary record

Isotopic evidence for mobility in the Copper and Bronze Age Cemetery of Humanejos (Parla, Madrid): a diachronic approach using biological and archaeological variables

Over the last several decades, the application of aDNA and strontium isotope analyses on archaeologically recovered human remains has provided new avenues for the investigation of mobility in past societies. Data on human mobility can be valuable in the reconstruction of prehistoric residential patterns and kinship systems, which are at the center of human social organization and vary across time and space. In this paper, we aim to contribute to our understanding of mobility, residence, and kinship patterns in late Prehistoric Iberia (c. 3300–1400BC) by providing new strontium data on 44 individuals from the site of Humanejos (Parla, Madrid). The study presented here is multi-proxy and looks at these new data by interweaving biological, chronological, and archaeological information. This analysis found that 7/44 individuals buried at Humanejos could be identified as non-local to the necropolis. Although more men (n = 5) than women (n = 2) were found in the non-local category, and more non-local individuals were identified in the pre-Bell Beaker (n = 5) than in Bell Beaker (n = 1) or Bronze Age (n = 1), we find no statistically significant differences concerning sex or time period. This contrasts with other archaeological datasets for late prehistoric Europe which suggest higher female mobility, female exogamy, and male-centered residential patterns were common. At Humanejos, we have also identified one non-local female whose exceptional Beaker grave goods suggest she was an individual of special status, leading to additional questions about the relationships between gender, mobility, and social position in this region and time periodThe project leading to this publication has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie Grant Agreement No 891776, project “WOMAM. Women, Men and Mobility: Understanding Gender Inequality in Prehistory.” This article was also supported by the Spanish Ministerio de Ciencia e Innovación Grants No. PID2019-105690 GB-I00 and HAR2013- 47776-R, the Dirección General de Patrimonio Cultural (Comunidad de Madrid) and the SFB 1070 “Ressourcenkulturen” (DFG

Aeromonas spp.-mediated cell-contact cytotoxicity is associated with the presence of type III secretion system

In the study we examined the production of cytotonic and cytotoxic toxins and the presence of a type III secretion system (TTSS) in 64 Aeromonas spp. strains isolated from fecal specimens of patients with gastroenteritis. We observed that contact of the bacteria with host epithelial cells is a prerequisite for their cytotoxicity at 3 h incubation. Cell-contact cytotoxic activity of the strains was strongly associated with the presence of the TTSS. Culture supernatants of the strains induced low cytotoxicity effects at the same time of incubation. Cell-free supernatants of 61 (95%) isolates expressed cytotoxic activity which caused the destruction of HEp-2 cells at 24 h. Moreover, 44% strains were cytotonic towards CHO cells and 46% of strains invaded epithelial cells

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Current European Labyrinthula zosterae Are Not Virulent and Modulate Seagrass (Zostera marina) Defense Gene Expression

Pro- and eukaryotic microbes associated with multi-cellular organisms are receiving increasing attention as a driving factor in ecosystems. Endophytes in plants can change host performance by altering nutrient uptake, secondary metabolite production or defense mechanisms. Recent studies detected widespread prevalence of Labyrinthula zosterae in European Zostera marina meadows, a protist that allegedly caused a massive amphi-Atlantic seagrass die-off event in the 1930's, while showing only limited virulence today. As a limiting factor for pathogenicity, we investigated genotype×genotype interactions of host and pathogen from different regions (10–100 km-scale) through reciprocal infection. Although the endophyte rapidly infected Z. marina, we found little evidence that Z. marina was negatively impacted by L. zosterae. Instead Z. marina showed enhanced leaf growth and kept endophyte abundance low. Moreover, we found almost no interaction of protist×eelgrass-origin on different parameters of L. zosterae virulence/Z. marina performance, and also no increase in mortality after experimental infection. In a target gene approach, we identified a significant down-regulation in the expression of 6/11 genes from the defense cascade of Z. marina after real-time quantitative PCR, revealing strong immune modulation of the host's defense by a potential parasite for the first time in a marine plant. Nevertheless, one gene involved in phenol synthesis was strongly up-regulated, indicating that Z. marina plants were probably able to control the level of infection. There was no change in expression in a general stress indicator gene (HSP70). Mean L. zosterae abundances decreased below 10% after 16 days of experimental runtime. We conclude that under non-stress conditions L. zosterae infection in the study region is not associated with substantial virulence

Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis

BACKGROUND Two phase 3 trials (UNCOVER-2 and UNCOVER-3) showed that at 12 weeks of treatment, ixekizumab, a monoclonal antibody against interleukin-17A, was superior to placebo and etanercept in the treatment of moderate-to-severe psoriasis. We report the 60-week data from the UNCOVER-2 and UNCOVER-3 trials, as well as 12-week and 60-week data from a third phase 3 trial, UNCOVER-1. METHODS We randomly assigned 1296 patients in the UNCOVER-1 trial, 1224 patients in the UNCOVER-2 trial, and 1346 patients in the UNCOVER-3 trial to receive subcutaneous injections of placebo (placebo group), 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg (2-wk dosing group), or 80 mg of ixekizumab every 4 weeks after a starting dose of 160 mg (4-wk dosing group). Additional cohorts in the UNCOVER-2 and UNCOVER-3 trials were randomly assigned to receive 50 mg of etanercept twice weekly. At week 12 in the UNCOVER-3 trial, the patients entered a long-term extension period during which they received 80 mg of ixekizumab every 4 weeks through week 60; at week 12 in the UNCOVER-1 and UNCOVER-2 trials, the patients who had a response to ixekizumab (defined as a static Physicians Global Assessment [sPGA] score of 0 [clear] or 1 [minimal psoriasis]) were randomly reassigned to receive placebo, 80 mg of ixekizumab every 4 weeks, or 80 mg of ixekizumab every 12 weeks through week 60. Coprimary end points were the percentage of patients who had a score on the sPGA of 0 or 1 and a 75% or greater reduction from baseline in Psoriasis Area and Severity Index (PASI 75) at week 12. RESULTS In the UNCOVER-1 trial, at week 12, the patients had better responses to ixekizumab than to placebo; in the 2-wk dosing group, 81.8% had an sPGA score of 0 or 1 and 89.1% had a PASI 75 response; in the 4-wk dosing group, the respective rates were 76.4% and 82.6%; and in the placebo group, the rates were 3.2% and 3.9% (P<0.001 for all comparisons of ixekizumab with placebo). In the UNCOVER-1 and UNCOVER-2 trials, among the patients who were randomly reassigned at week 12 to receive 80 mg of ixekizumab every 4 weeks, 80 mg of ixekizumab every 12 weeks, or placebo, an sPGA score of 0 or 1 was maintained by 73.8%, 39.0%, and 7.0% of the patients, respectively. Patients in the UNCOVER-3 trial received continuous treatment of ixekizumab from weeks 0 through 60, and at week 60, at least 73% had an sPGA score of 0 or 1 and at least 80% had a PASI 75 response. Adverse events reported during ixekizumab use included neutropenia, candidal infections, and inflammatory bowel disease. CONCLUSIONS In three phase 3 trials involving patients with psoriasis, ixekizumab was effective through 60 weeks of treatment. As with any treatment, the benefits need to be weighed against the risks of adverse events. The efficacy and safety of ixekizumab beyond 60 weeks of treatment are not yet known