152 research outputs found

    Reservoir architecture and heterogeneity distribution in floodplain sandstones: Key features in outcrop, core and wireline logs

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    Exploration and production from formations deposited in low-gradient fluvial systems is typically associated with a high degree of uncertainty; a reflection of the inherent characteristics of these environments, notably the dominance of non-reservoir floodplain fines, rapid lateral facies variations and associated heterogeneities at different scales. However, for a field development to be successful it becomes crucial to know the location, geometry, dimensions and connectivity of the most permeable facies, related to the main channel and the associated proximal overbank deposits (crevasse-splay complexes). With the aim of addressing this problem, a multi-disciplinary study is presented, combining outcrop data, high-resolution sedimentological descriptions and advanced visualization techniques based on Digital Outcrop Models. This is compared with subsurface data from behind the outcrop (core, gamma ray and borehole image logs). The Mudstone–Sandstone Unit of the Triassic Red Beds of Iberian Meseta formation in south-central Spain was selected for the present study. The unit is characterized by the lateral and vertical stacking of four architectural elements: (i) channelized sandstone bodies; (ii) asymmetrical sigmoidal-shaped sandstone bodies; (iii) lobe-shaped to sheet-like sandstone bodies; and (iv) sheet-like mudstones. These elements represent meandering channel, crevasse-channel-splay and floodplain sub-environments, comprising a distal, low-gradient meandering fluvial system. Together with well-documented outcrop and core facies, calibrated log responses are also presented for the channel bodies (bell-shape Gamma Ray profile, random azimuths and low to high dip angles), the crevasse-splay bodies (funnel-shape Gamma Ray profile, unidirectional azimuths and low dip angles) and the floodplain deposits (serrated Gamma Ray profile, unidirectional azimuths and very low dip angles). The full integration of outcrop and subsurface datasets has enabled generation of a robust conceptual model with predictive potential when establishing the three-dimensional stacking of facies, distribution of heterogeneities, and the connectivity between reservoir rock geobodies of primary (channel) and secondary (crevasse complex) interest in this type of fluvial reservoir.Fil: Yeste, Luis Miguel. Universidad de Granada. Facultad de Ciencias. Departamento de Estratigrafía y Paleontología.; EspañaFil: Varela, Augusto Nicolás. YPF - Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Viseras, César. Universidad de Granada. Facultad de Ciencias. Departamento de Estratigrafía y Paleontología.; EspañaFil: Mcdougall, Neil D.. No especifíca;Fil: García García, Fernando. Universidad de Granada. Facultad de Ciencias. Departamento de Estratigrafía y Paleontología.; Españ

    Lab-on-a-Chip Analysis Using Benchtop NMR Technology

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    We present the design and optimization of a benchtop NMR spectrometer for real-time metabolic monitoring of 3D tissue on microfluidic platforms, utilizing hyperpolarization via dynamic nuclear polarisation. We show the modifications made to a commercial benchtop NMR spectrometer, the design and fabrication of a microfluidic platform ensuring consistent injection of hyperpolarized substrates and ongoing cell media renewal, and its integration with a radio frequency (RF) coil for data transmission and reception (Tx/Rx). Additionally, the construction of a sample carrier is presented. Preliminary NMR results from this system are also provided.This work has received funding from: The European Union’s Horizon 2020 research and innovation program (GA-863037); the Spanish grants with reference PID2020- 117859RA-I00 funded by MCIN/AEI/10.13039/501100011033 (NARMYD), RYC2020-029099-I funded by MCIN/AEI10.13039/501100011033 and by “ESF Investing in your future”, PLEC2022-009256 funded by MCIN/AEI/10.13039/501100011033 and by the “European Union NextGenerationEU/PRTR”; The BIST (Barcelona Institute of Science and Technology)-“la Caixa” Banking Foundation Chemical Biology programme

    Safety outcomes during pediatric GH therapy: final results from the prospective GeNeSIS observational program

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    CONTEXT: Safety concerns regarding premature mortality, diabetes, neoplasia and cerebrovascular disease in association with growth hormone (GH) therapy have been raised. OBJECTIVE: To assess incidence of key safety outcomes. DESIGN: Prospective, multinational, observational study (1999-2015). SETTING: 22,311 GH-treated children from 827 investigative sites in 30 countries. PATIENTS: Children with growth disorders. INTERVENTIONS: GH treatment. MAIN OUTCOME MEASURES: Standardized mortality (SMR) and incidence (SIR) ratios with 95% confidence intervals (CI) for mortality, diabetes, and primary cancer, using general population registries. RESULTS: Predominant short stature diagnoses were GH deficiency (63%), idiopathic short stature (13%), and Turner syndrome (8%), with mean±SD follow-up of 4.2±3.2 years (∼92,000 person-years [PY]). Forty-two deaths occurred in patients with follow-up, with SMR (95% CI) of 0.61 (0.44-0.82); the SMR was elevated for patients with cancer-related organic GH deficiency (5.87 [3.21-9.85]). Based on 18 cases, Type 2 diabetes (T2DM) risk was elevated (SIR 3.77 [2.24-5.96]), but 72% had risk factors. In patients without cancer history, 14 primary cancers were observed (SIR 0.71 [0.39-1.20]). Second neoplasms occurred in 31/622 (5.0%) cancer survivors (10.7 [7.5-15.2] cases/1000 PY), and intracranial tumor recurrences in 67/823 (8.1%) tumor survivors (16.9 [13.3-21.5] cases/1000 PY). All 3 hemorrhagic stroke cases had risk factors. CONCLUSIONS: GeNeSIS data support the favourable safety profile of pediatric GH treatment. Overall risk for death or primary cancer was not elevated in GH-treated children, and no hemorrhagic strokes occurred in patients without risk factors. T2DM incidence was elevated compared to the general population, but most cases had diabetes risk factors

    Identification of FBXL4 as a Metastasis Associated Gene in Prostate Cancer

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    Prostate cancer is the most common cancer among western men, with a significant mortality and morbidity reported for advanced metastatic disease. Current understanding of metastatic disease is limited due to difficulty of sampling as prostate cancer mainly metastasizes to bone. By analysing prostate cancer bone metastases using high density microarrays, we found a common genomic copy number loss at 6q16.1–16.2, containing the FBXL4 gene, which was confirmed in larger series of bone metastases by fluorescence in situ hybridisation (FISH). Loss of FBXL4 was also detected in primary tumours and it was highly associated with prognostic factors including high Gleason score, clinical stage, prostate-specific antigen (PSA) and extent of disease, as well as poor patient survival, suggesting that FBXL4 loss contributes to prostate cancer progression. We also demonstrated that FBXL4 deletion is detectable in circulating tumour cells (CTCs), making it a potential prognostic biomarker by ‘liquid biopsy’. In vitro analysis showed that FBXL4 plays a role in regulating the migration and invasion of prostate cancer cells. FBXL4 potentially controls cancer metastasis through regulation of ERLEC1 levels. Therefore, FBXL4 could be a potential novel prostate cancer suppressor gene, which may prevent cancer progression and metastasis through controlling cell invasion

    Venous thromboembolism in Cushing syndrome:results from an EuRRECa and Endo-ERN survey

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    Background: Patients with Cushing syndrome (CS) are at increased risk of venous thromboembolism (VTE). Objective: The aim was to evaluate the current management of new cases of CS with a focus on VTE and thromboprophylaxis. Design and methods: A survey was conducted within those that report in the electronic reporting tool (e-REC) of the European Registries for Rare Endocrine Conditions (EuRRECa) and the involved main thematic groups (MTG’s) of the European Reference Networks for Rare Endocrine Disorders (Endo-ERN) on new patients with CS from January 2021 to July 2022. Results: Of 222 patients (mean age 44 years, 165 females), 141 patients had Cushing disease (64%), 69 adrenal CS (31%), and 12 patients with ectopic CS (5.4%). The mean follow-up period post-CS diagnosis was 15 months (range 3–30). Cortisol-lowering medications were initiated in 38% of patients. One hundred fifty-four patients (69%) received thromboprophylaxis (including patients on chronic anticoagulant treatment), of which low-molecular-weight heparins were used in 96% of cases. VTE was reported in six patients (2.7%), of which one was fatal: two long before CS diagnosis, two between diagnosis and surgery, and two postoperatively. Three patients were using thromboprophylaxis at time of the VTE diagnosis. The incidence rate of VTE in patients after Cushing syndrome diagnosis in our study cohort was 14.6 (95% CI 5.5; 38.6) per 1000 person-years. Conclusion: Thirty percent of patients with CS did not receive preoperative thromboprophylaxis during their active disease stage, and half of the VTE cases even occurred during this stage despite thromboprophylaxis. Prospective trials to establish the optimal thromboprophylaxis strategy in CS patients are highly needed. Significance statement The incidence rate of venous thromboembolism in our study cohort was 14.6 (95% CI 5.5; 38.6) per 1000 person-years. Notably, this survey showed that there is great heterogeneity regarding time of initiation and duration of thromboprophylaxis in expert centers throughout Europe.</p

    High-throughput assay for determining enantiomeric excess of chiral diols, amino alcohols, and amines and for direct asymmetric reaction screening

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    Determining enantiomeric excess (e.e.) in chiral compounds is key to development of chiral catalyst auxiliaries and chiral drugs. Here we describe a sensitive and robust fluorescence-based assay for determining e.e. in mixtures of enantiomers of 1,2- and 1,3-diols, chiral amines, amino alcohols, and amino-acid esters. The method is based on dynamic self-assembly of commercially available chiral amines, 2-formylphenylboronic acid, and chiral diols in acetonitrile to form fluorescent diastereomeric complexes. Each analyte enantiomer engenders a diastereomer with distinct fluorescence wavelength/intensity originating from enantiopure fluorescent ligands. In this assay, enantiomers of amines and amine derivatives assemble with diol-type ligands containing a binaphthol moiety (BINOL and VANOL), whereas diol enantiomers form complexes with the enantiopure amine-type fluorescent ligand tryptophanol. The differential fluorescence is utilized to determine the amount of each enantiomer in the mixture with an error of &lt;1% e.e. This method enables high-throughput real-time evaluation of enantiomeric/diastereomeric excess (e.e./d.e.) and product yield of crude asymmetric reaction products. The procedure comprises high-throughput liquid dispensing of three components into 384-well plates and recording of fluorescence using an automated plate reader. The approach enables scaling up the screening of combinatorial libraries and, together with parallel synthesis, creates a robust platform for discovering chiral catalysts or auxiliaries for asymmetric transformations and chiral drug development. The procedure takes ~4–6 h and requires 10–20 ng of substrate per well. Our fluorescence-based assay offers distinct advantages over existing methods because it is not sensitive to the presence of common additives/impurities or unreacted/incompletely utilized reagents or catalysts.</p

    ILC3 function as a double-edged sword in inflammatory bowel diseases

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    Inflammatory bowel diseases (IBD), composed mainly of Crohn’s disease (CD) and ulcerative colitis (UC), are strongly implicated in the development of intestinal inflammation lesions. Its exact etiology and pathogenesis are still undetermined. Recently accumulating evidence supports that group 3 innate lymphoid cells (ILC3) are responsible for gastrointestinal mucosal homeostasis through moderate generation of IL-22, IL-17, and GM-CSF in the physiological state. ILC3 contribute to the progression and aggravation of IBD while both IL-22 and IL-17, along with IFN-γ, are overexpressed by the dysregulation of NCR− ILC3 or NCR+ ILC3 function and the bias of NCR+ ILC3 towards ILC1 as well as regulatory ILC dysfunction in the pathological state. Herein, we feature the group 3 innate lymphoid cells’ development, biological function, maintenance of gut homeostasis, mediation of IBD occurrence, and potential application to IBD therapy
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