Radiocarbon Dates for Las Chimeneas (Cantabria, Spain) Palaeolithic Cave Art: Quality of Radiocarbon and Relevance to Parietal Art

AMS radiocarbon dating has been widely applied in Palaeolithic art research and its value has been proven over the past three decades. Yet it still suffers from issues that need to be discussed and analysed to improve future sampling strategies and strengthen the interpretation of the results. This study presents new AMS dates for the parietal art in Cueva de Las Chimeneas in northern Spain, describes the quality of the samples, and discusses their reliability. The joint assessment of the dates and its comparison with previously obtained dates as well as stratified and dated portable art makes it possible to put forward a hypothesis about the time of creation of the cave's parietal art and the degree of synchrony or diachrony in its production. Consequently, it is proposed that the cave art at Las Chimeneas was created in the lower Magdalenian, between 19,000 and 17,500 cal BP

Time delay in the acquisition of verbal correspondence in adults: An exploratory study

A correspondência Dizer-Fazer é normalmente definida como um indivíduo que faz o que disse que faria e relata com precisão o que fez. Este estudo avalia os efeitos do atraso entre as respostas de correspondência verbal (dizer, fazer, relatar). Foram avaliados os efeitos do atraso temporal entre as respostas de correspondência (Dizer, Fazer e Relatar) em um procedimento de correspondência típico. Oito adultos foram atribuídos a um de dois grupos que foram diferenciados por atraso: Grupo não atrasado (i.e., 0 horas entre as respostas), Grupo atrasado (i.e., 24 horas entre as respostas). A tarefa consistia em três condições: 1) Dizer (respondendo a perguntas), 2) Fazer (realizando ações diferentes em relação a Dizer), 3) Relatar (respondendo a perguntas sobre o Fazer). Diferenças foram encontradas entre os dois grupos, sendo que o Grupo Atrasado apresentou menores percentuais de correspondência. No entanto, nenhuma diferença significativa foi encontrada entre os grupos. A discussão é realizada em termos do aumento no valor da variável de atraso e da relevância do atraso no emparelhamento em contextos clínicos.Palavras-Chaves: correspondência verbal; dizer-fazer; fazer-relatar; atraso temporal; adultos. Say-Do correspondence is typically defined as individuals’ doing what they said they would do and accurately reporting what they did. The present study evaluated the effects of the delay between responses of verbal correspondence (Say, Do, Report) and the relation among responses (Say-Do, Do-Report, Say-Report, and Say-Do-Report) in a correspondence procedure. Eight adults were assigned to one of two groups that were differentiated by the delay among responses: Non-Delayed group (i.e., 0 hours among responses), Delayed group (i.e., 24 hours among responses). The correspondence task consisted of three phases: (1) Say (answering questions), (2) Do (performing different actions in relation to Say), and (3) Report (answering questions about Do). The Delayed group presented lower percentages of correspondence, but no statistically significant differences were found between groups. We discuss the increase in value of the delay variable and relevance of this delay to matching in clinical contexts.Keywords: Verbal correspondence; Say-Do; Do-Report; temporal delay; adults

BARD1 Pathogenic Variants are Associated with Triple-Negative Breast Cancer in a Spanish Hereditary Breast and Ovarian Cancer Cohort

Only a small fraction of hereditary breast and/or ovarian cancer (HBOC) cases are caused by germline variants in the high-penetrance breast cancer 1 and 2 genes (BRCA1 and BRCA2). BRCA1-associated ring domain 1 (BARD1), nuclear partner of BRCA1, has been suggested as a potential HBOC risk gene, although its prevalence and penetrance are variable according to populations and type of tumor. We aimed to investigate the prevalence of BARD1 truncating variants in a cohort of patients with clinical suspicion of HBOC. A comprehensive BARD1 screening by multigene panel analysis was performed in 4015 unrelated patients according to our regional guidelines for genetic testing in hereditary cancer. In addition, 51,202 Genome Aggregation Database (gnomAD) non-Finnish, non-cancer European individuals were used as a control population. In our patient cohort, we identified 19 patients with heterozygous BARD1 truncating variants (0.47%), whereas the frequency observed in the gnomAD controls was 0.12%. We found a statistically significant association of truncating BARD1 variants with overall risk (odds ratio (OR) = 3.78; CI = 2.10-6.48; p = 1.16 x 10(-5)). This association remained significant in the hereditary breast cancer (HBC) group (OR = 4.18; CI = 2.10-7.70; p = 5.45 x 10(-5)). Furthermore, deleterious BARD1 variants were enriched among triple-negative BC patients (OR = 5.40; CI = 1.77-18.15; p = 0.001) compared to other BC subtypes. Our results support the role of BARD1 as a moderate penetrance BC predisposing gene and highlight a stronger association with triple-negative tumors

A Web-Based Automated Image Processing Research Platform for Cochlear Implantation-Related Studies

International audienceThe robust delineation of the cochlea and its inner structures combined with the detection of the electrode of a cochlear implant within these structures is essential for envisaging a safer, more individualized, routine image-guided cochlear implant therapy. We present Nautilus—a web-based research platform for automated pre- and post-implantation cochlear analysis. Nautilus delineates cochlear structures from pre-operative clinical CT images by combining deep learning and Bayesian inference approaches. It enables the extraction of electrode locations from a post-operative CT image using convolutional neural networks and geometrical inference. By fusing pre- and post-operative images, Nautilus is able to provide a set of personalized pre- and post-operative metrics that can serve the exploration of clinically relevant questions in cochlear implantation therapy. In addition, Nautilus embeds a self-assessment module providing a confidence rating on the outputs of its pipeline. We present a detailed accuracy and robustness analyses of the tool on a carefully designed dataset. The results of these analyses provide legitimate grounds for envisaging the implementation of image-guided cochlear implant practices into routine clinical workflows

Dotes de doncellas pobres sevillanas y su influencia en la ciudad de Lima

The Cathedral of Seville, Hospital de las Cinco Llagas, Hospital de San Hermenegildo and Hermandad de la Misericordia provided welfare assistance to Castilian women of marriageable age, providing them not only with dowries, but also with social and economic support. The Hospitals in question also gave them the opportunity to learn a trade and supplied a temporary place to live a secluded life. The separation of the sexes led to the creation of a women’s infirmary, meaning the women could develop professionally as caregivers or carry out domestic chores. This practice was then taken to the Indies. Hospital de la Caridad in the ‘City of the Kings’, present-day Lima, in the Viceroyalty of Peru is a case in point.La Catedral Hispalense, el Hospital de las Cinco Llagas, el Hospital de San Hermenegildo y la Hermandad de la Misericordia ejercieron una labor asistencial a la mujer castellana núbil, ofreciendo a las doncellas no sólo dotes sino ayuda social y económica, y en el caso de los hospitales el aprendizaje de un oficio y un lugar donde vivir en reclusión de forma temporal para desarrollarse profesionalmente como cuidadoras, o realizando labores domésticas, ya que a causa de la separación de los sexos se formó la enfermería femenina. Esta costumbre fue trasladada a las Indias en concreto en el Hospital de la Caridad de la Ciudad de los Reyes en el Virreinato del Perú

Pancreatic metastases from renal cell carcinoma. Postoperative outcome after surgical treatment in a Spanish multicenter study (PANMEKID)

Background: Renal Cell Carcinoma (RCC) occasionally spreads to the pancreas. The purpose of our study is to evaluate the short and long-term results of a multicenter series in order to determine the effect of surgical treatment on the prognosis of these patients. Methods: Multicenter retrospective study of patients undergoing surgery for RCC pancreatic metastases, from January 2010 to May 2020. Variables related to the primary tumor, demographics, clinical characteristics of metastasis, location in the pancreas, type of pancreatic resection performed and data on short and long-term evolution after pancreatic resection were collected. Results: The study included 116 patients. The mean time between nephrectomy and pancreatic metastases' resection was 87.35 months (ICR: 1.51-332.55). Distal pancreatectomy was the most performed technique employed (50 %). Postoperative morbidity was observed in 60.9 % of cases (Clavien-Dindo greater than IIIa in 14 %). The median follow-up time was 43 months (13-78). Overall survival (OS) rates at 1, 3, and 5 years were 96 %, 88 %, and 83 %, respectively. The disease-free survival (DFS) rate at 1, 3, and 5 years was 73 %, 49 %, and 35 %, respectively. Significant prognostic factors of relapse were a disease free interval of less than 10 years (2.05 [1.13-3.72], p 0.02) and a history of previous extrapancreatic metastasis (2.44 [1.22-4.86], p 0.01). Conclusions: Pancreatic resection if metastatic RCC is found in the pancreas is warranted to achieve higher overall survival and disease-free survival, even if extrapancreatic metastases were previously removed. The existence of intrapancreatic multifocal compromise does not always warrant the performance of a total pancreatectomy in order to improve survival. (C) 2021 The Authors. Published by Elsevier Ltd

Repeated pancreatic resection for pancreatic metastases from renal cell Carcinoma: A Spanish multicenter study (PANMEKID)

Background and objectives: Recurrent isolated pancreatic metastasis from Renal Cell Carcinoma (RCC) after pancreatic resection is rare. The purpose of our study is to describe a series of cases of relapse of pancreatic metastasis from renal cancer in the pancreatic remnant and its surgical treatment with a repeated pancreatic resection, and to analyse the results of both overall and disease -free survival. Methods: Multicenter retrospective study of patients undergoing pancreatic resection for RCC pancreatic metastases, from January 2010 to May 2020. Patients were grouped into two groups depending on whether they received a single pancreatic resection (SPS) or iterative pancreatic resection. Data on short and long-term outcome after pancreatic resection were collected. Results: The study included 131 pancreatic resections performed in 116 patients. Thus, iterative pancreatic surgery (IPS) was performed in 15 patients. The mean length of time between the first pancreatic surgery and the second was 48.9 months (95 % CI: 22.2-56.9). There were no differences in the rate of postoperative complications. The DFS rates at 1, 3 and 5 years were 86 %, 78 % and 78 % vs 75 %, 50 % and 37 % in the IPS and SPS group respectively (p = 0.179). OS rates at 1, 3, 5 and 7 years were 100 %, 100 %, 100 % and 75 % in the IPS group vs 95 %, 85 %, 80 % and 68 % in the SPS group (p = 0.895). Conclusion: Repeated pancreatic resection in case of relapse of pancreatic metastasis of RCC in the pancreatic remnant is justified, since it achieves OS results similar to those obtained after the first resection

HCV-coinfection is related to an increased HIV-1 reservoir size in cART-treated HIV patients: a cross-sectional study

In HIV-1/HCV-coinfected patients, chronic HCV infection leads to an increased T-lymphocyte immune activation compared to HIV-monoinfected patients, thereby likely contributing to increase HIV-1 reservoir that is the major barrier for its eradication. Our objective was to evaluate the influence of HCV coinfection in HIV-1 viral reservoir size in resting (r) CD4+ T-cells (CD25-CD69-HLADR-). Multicenter cross-sectional study of 97 cART-treated HIV-1 patients, including 36 patients with HIV and HCV-chronic co-infection without anti-HCV treatment, 32 HIV patients with HCV spontaneous clearance and 29 HIV-monoinfected patients. rCD4+ T-cells were isolated and total DNA was extracted. HIV viral reservoir was measured by Alu-LTR qPCR. Differences between groups were calculated with a generalized linear model. Overall, 63.9% were men, median age of 41 years and Caucasian. Median CD4+ and CD8+ T-lymphocytes were 725 and 858 cells/mm 3 , respectively. CD4+ T nadir cells was 305 cells/mm 3 . Proviral HIV-1 DNA size was significantly increased in chronic HIV/HCV-coinfected compared to HIV-monoinfected patients (206.21 ± 47.38 vs. 87.34 ± 22.46, respectively; P = 0.009), as well as in spontaneously clarified HCV co-infected patients when compared to HIV-monoinfected individuals (136.20 ± 33.20; P = 0.009). HIV-1/HCV co-infected patients showed a larger HIV-1 reservoir size in comparison to HIV-monoinfected individuals. This increase could lead to a greater complexity in the elimination of HIV-1 reservoir in HIV-1/HCV-coinfected individuals, which should be considered in the current strategies for the elimination of HIV-1 reservoir.Financial support was provided by the Instituto de Salud Carlos III to VB (PI15CIII/00031), by the Spanish Ministry of Economy and Competitiveness to MC (SAF2016–78480-R) and The SPANISH AIDS Research Network RD16CIII/0002/0001, RD16CIII/0002/0002 and RD16/0025/0013 - ISCIII – FEDER. MRLP is supported by ISCIII - Subdirección General de Evaluacion and European Funding for Regional Development (FEDER) (PIE 13/00040 and RD12/0017/0017 RETIC de SIDA). C.P. is supported by the Portuguese Fundação para a Ciência e Tecnologia (FCT) (grant number SFRH/ BPD/77448/2011 is part of the EDCTP2 programme supported by the European Union). V.B., A.F.R. and N.R. are supported by the Miguel Servet programme from Fondo de Investigación Sanitaria (ISCIII) (grant number CP13/00098, CP14/CIII/00010 and CP14/00198, respectively)

COVID-19 vaccine failure

COVID-19 affects the population unequally with a higher impact on aged and immunosuppressed people. Hence, we assessed the effect of SARS-CoV-2 vaccination in immune compromised patients (older adults and oncohematologic patients), compared with healthy counterparts. While the acquired humoral and cellular memory did not predict subsequent infection 18 months after full immunization, spectral and computational cytometry revealed several subsets within the CD8+ T-cells, B-cells, NK cells, monocytes and CD45RA+ CCR7- Tγδ cells differentially expressed in further infected and non-infected individuals not just following immunization, but also prior to that. Of note, up to 7 subsets were found within the CD45RA+ CCR7- Tγδ population with some of them being expanded and other decreased in subsequently infected individuals. Moreover, some of these subsets also predicted COVID-induced hospitalization in oncohematologic patients. Therefore, we hereby have identified several cellular subsets that, even before vaccination, strongly related to COVID-19 vulnerability as opposed to the acquisition of cellular and/or humoral memory following vaccination with SARS-CoV2 mRNA vaccines.This study has been funded through Programa Estratégico Instituto de Biología y Genética Molecular (IBGM Junta de Castilla y León. Ref. CCVC8485), Junta de Castilla y León (Proyectos COVID 07.04.467B04.74011.0) and the European Commission – NextGenerationEU (Regulation EU 2020/2094), through CSIC's Global Health Platform (PTI Salud Global; SGL21-03-026 and SGL2021-03-038)N

Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification