Late cretaceous stratigraphy of the southeastern Chaco - Paraná basin (“norte basin” - Uruguay). The maastrichtian age of the calcretization process

In the last 40 years, successive revisions have been introduced to the lithostratigraphy of the Late Cretaceous of the Norte Basin, whose record is formed by predominantly siliciclastic continental fossiliferous sedimentary rocks. A factor that contributed to the terminology proliferation was the misplaced importance attributed to the epigenetic processes and products (calcretes and ferricretes, occasionally fossiliferous) affecting those siliciclastic rocks. Based on field work and lithological logs from a number of key areas, the validity of the original stratigraphic column showing, from base to top, the Guichón, Mercedes, Asencio and Queguay formations is supported. For those particular units, the lithostratigraphic scope given by the original definitions is correct and, with minimum adjustments, they should be restored for their practical usefulness as geological mapping units. An evolutionary scheme for the Late Cretaceous of the Norte Basin is herein presented, with the aim of contributing to a greater understanding of the succession of sedimentary and epigenetic processes. A Maastrichtian age is proposed for the carbonatic cementation and/or substitution that affected the Mercedes and Asencio formations, thus originating the Queguay Formation, based on absolute age of the calcite cement (~ 72 Ma; U-Pb), paleontological data, and the correlation established with similar events recorded in the Marília Formation on the Bauru Basin (Brazil)

Identification of novel synthetic lethal vulnerability in non small cell lung cancer by co targeting TMPRSS4 and DDR1

Finding novel targets in non-small cell lung cancer (NSCLC) is highly needed and identification of synthetic lethality between two genes is a new approach to target NSCLC. We previously found that TMPRSS4 promotes NSCLC growth and constitutes a prognostic biomarker. Here, through large-scale analyses across 5 public databases we identified consistent co-expression between TMPRSS4 and DDR1. Similar to TMPRSS4, DDR1 promoter was hypomethylated in NSCLC in 3 independent cohorts and hypomethylation was an independent prognostic factor of disease-free survival. Treatment with 5-azacitidine increased DDR1 levels in cell lines, suggesting an epigenetic regulation. Cells lacking TMPRSS4 were highly sensitive to the cytotoxic effect of the DDR1 inhibitor dasatinib. TMPRSS4/DDR1 double knock-down (KD) cells, but not single KD cells suffered a G0/G1 cell cycle arrest with loss of E2F1 and cyclins A and B, increased p21 levels and a larger number of cells in apoptosis. Moreover, double KD cells were highly sensitized to cisplatin, which caused massive apoptosis (~40%). In vivo studies demonstrated tumor regression in double KD-injected mice. In conclusion, we have identified a novel vulnerability in NSCLC resulting from a synthetic lethal interaction between DDR1 and TMPRSS4

Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses

BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million personyears of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eG FR values 105 mL.min(-1).1.73 m(-2), compared with those with eG FR between 60 and 105 mL.min(-1).1.73 m(-2). Mendelian randomization analyses for CHD showed an association among participants with eGFR 105 mL.min(-1).1.73 m(-2). Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin Alc, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Image quality and dose evaluation in spiral chest CT examinations of patients with lung carcinoma

A study was undertaken to assess the quality of general chest CT examinations for indication of lung carcinoma according to the criteria proposed in the European Commission (EC) Guidelines, and to investigate their usefulness in the optimization of this practice. The criteria were evaluated for a sample of 100 examinations from five radiology departments in the Madrid area featuring single slice helical CT scanners with special emphasis on radiation dose and image quality. To determine the degree of compliance with the image criteria considered, the examinations were independently evaluated twice by five radiologists from the participating centres. A subsequent selection of the observers was made according to the consistency and independence of their readings. Dose measurements carried out in parallel supplied data to estimate the values of the CT dose indices (CTDI), dose-length product (DLP) and effective dose (E). The results show good compliance with the image criteria used - between 93% and 98% on average at the different sites, with variable degrees of internal deviation. 10 out of a total of 16 criteria proposed in the EC guidelines were met by practically all the examinations in the sample. The average weighted CTDI (CTDIw) values per site were in the range of 13-19 mGy; those of DLP were between 263 mGy cm and 577 mGy cm, and those of effective dose between 4 mSv and 9 mSv. The highest mean DLP value was below but close to the reference value proposed in the EC Document (650 mGy cm). In general, a weak correlation or no correlation at all was found between image quality scores and patient dose (DLP)

Valoración de calidad de imagen y dosis en exámenes de tomografía computarizada helicoidal de abdomen y de pelvis en pacientes con linfoma

Objective: The aim of this study is to evaluate the quality of pelvic and abdominal CT images performed for lymphoma according to the criteria proposed in the European Commission Guidelines on radiation imaging. (En castellano dice: la Guia de la Comisión Europea. Lo que pasa es que hay muchas guias publicadas por la Comisión: aseguranse que sea esta la citada) Material and methods: The criteria were evaluated in a sample of 100 patients attended at five public hospitals in the Autonomous Community of Madrid. All patients underwent single-slice helical CT studies. Fulfillment of the imaging criteria in the selected images was evaluated by five radiologists, one from each center, working independently. The Index of Image Quality (IIQ) was determined for the complete abdominal and pelvic examination. The dose was also measured to estimate the values of the CT Dose Index (CTDIw), Dose by Length Product (DLP), and effective dose (E). Results: A high rate of fulfillment of the criteria was found for individual abdominal images. In the pelvis, the rate of fulfillment was lower, especially for three criteria. The IIQ for each center was between 83%-92%, with variable degrees of internal deviation. The mean values of CTDIw per center were between 16-23 mGy; DLP values were between 430 and 750 mGy cm, and the effective dose was 7-12 mSv. In general, no correlation was found between IIQ and dose per patient, either for the entire sample (r = 0.04) or by centers (r£0.36). Conclusions: The utility of the European Union's Quality Criteria was confirmed. We have elaborated a single list of criteria of image quality and suggest reference dosage levels for abdominal-pelvic CT examinations in patients with lymphoma

Evaluación de la calidad de los exámenes de tomografía computarizada de cerebro en la indicación de accidente cerebrovascular agudo

Objectives. Our objective was to apply quality criteria proposed by the European Commission (EC) Guidelines to the brain CT examinations for cerebrovascular accident (CVA) diagnosis at single-slice spiral CT scanners from five different hospitals in the Madrid area. Material and methods. A sample of 100 brain CT examinations was collected and independently reviewed by five radiologists, to determine the degree of fulfilment of image quality criteria. Dose measurements were performed to estimate the values of the CT dose indexes (CTDIw, CTDIair), the dose length product (DLP), and the effective dose (E). Results. Once the McNemar test was applied to the sample, the number of observers' readings was reduced to three. The quality criteria were, in general, fulfilled, since mean values of image quality score between 80% and 92% were deduced, with variation coefficients per centre in the range of 0.07-0.1. However, both visualization criteria 1.1.2 and 1.1.3 exhibited similar ranges of fulfillment (38% - 94%). The good compliance with critical reproduction criteria in the study reflected the capability of these CT scanners to create images of adequate quality, although optimisation should be achieved in some of the centres. Concerning radiation exposure, the mean values per centre of the dose quantities were in the range of 42-64 mGy for the weighted CTDI (CTDIw), 423-744 mGy-cm for DLP, and 1.1-1.9 mSv for E. Conclusions. The mean values at three centres were close to but above the reference value proposed by the EC Guidelines for CTDIw (60 mGy), and lower than the corresponding reference level for DLP (1050 mGy·cm). Dose optimisation techniques focused on the adjustment of the CTDIw-related examination parameters were proposed

Evaluación de la calidad de los exámenes de tomografía computarizada de columna lumbar en la indicación de hernia discal

Aim: To apply quality criteria of computerized tomography (CT) of the lumbar spine as defined in the European Guidelines, in four hospitals of the Community of Madrid, using spiral CT (SCT) in the clinical indication of disc hernia. Materials and Methods: There were selected 20 lumbar spine studies from each center. These were evaluated by five independent radiologists in order to determine the degree of adherence to criteria quality of the European Guidelines for such studies. Dosimetric measurements were performed in parallel in order to estimate values of CT dose index (CTDIw), dose length product (DLP) and effective dose for each patient. Results: The results showed a high degree of adherence to image quality criteria in four centers (97-100)%. Median CTDIw values per center were (34-60) mGy; those of DLP were (242-499) mGy·cm, and those of effective dose between 4 and 7 mSv. Conclusion: There has been a good adherence to the quality criteria. In some cases, however, it seems that doses could very well be reduced through a re-thinking of the protocols

Evaluación de la calidad de imagen y de la dosis en exámenes de TC helicoidal de tórax en pacientes con carcinoma de pulmón. Resultados preliminares.

We have applied criteria for CT quality defined in the European Guidelines to a sample of thoracic CT examinations - for the indication of pulmonary carcinoma - of 5 institutions of the Community of Madrid that have spiral CT equipment. The selected examinations have been evaluated independently by five radiologists to determine the degree of adherence to the quality criteria for image defined in the Guideliness for examinations of general thorax. Dosimetric measurements carried out in parallel have served to estimate the values of CT (CTDIw) dose indices, dose-length product (DLP) and effective dose for every patient. The results show a high global adherence to the quality criteria (96%), with averages per institution being between 94% (in two institutions) and 98% (in three institutions). There are 10 of 16 criteria that are adhered to in all examinations of the sample; those which are not adhered to systematically are: two of visualization (1.1 and 1.4), with 92-96% fulfillment, and four of critical reproduction (2.6; 2.8; 2.9 and 2.10), with percentages of adherence between 91% and 96%. The average CTDIw values per institution are in the interval 12.9-19.1 mGy; those of DLP between 263 and 577 mGy cm and those of effective dose between 4.2 and 9.2 mSv. The DLP-image quality correlation in institutions with the best image quality was null in two of them and direct and moderate in the third. In both institutions with the poorest image quality, the correlation was inverse and moderate in one and direct and weak in the other. Reasons for these results are analyzed, as well as possible ways of optimizing quality in relation to dose and parameters used