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Deep, underground repositories are needed to isolate radioactive waste from the biosphere. Because bentonite is an integral component of many multibarrier repository systems, information on the hydraulic behavior of bentonite is crucial for modeling the long-term viability of such systems. In this paper the hydraulic behavior of bentonite samples was analyzed as a function of aggregate size, and samples were subjected to hydrothermal treatments involving contact with NaCl, KCl, and deionized water. Neutron and X-ray imaging were used to quantify water sorption into packed bentonite samples and bentonite swelling into the water column. The distance between the original clay-water interface and the wetting front was determined as a function of time. Average water uptake exhibited a square-root-of-time dependence in freshly prepared samples, but more variable rates were observed for samples previously in contact with water. The radiography was supported by small-angle neutron scattering analysis and ultra-small-angle neutron scattering analysis of aggregate size distributions and by inelastic neutron scattering to understand the physicochemical environment of the sorbed water. Results showed that hydrothermal treatment with KCl had the greatest effect of increased water transport in the bentonite, possibly as a result of the interaction of K+ with smectite layers in the clay.
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Surgical resection with free surgical margins is the cornerstone of successful primary treatment of vulvar squamous cell carcinoma (VSCC). In general reexcision is recommended when the minimum peripheral surgical margin (MPSM) is <8 mm microscopically. Pathologists are, therefore, required to report the minimum distance from the tumor to the surgical margin. Currently, there are no guidelines on how to make this measurement, as this is often considered straightforward. However, during the 2018 Annual Meeting of the British Association of Gynaecological Pathologists (BAGP), a discussion on this topic revealed a variety of opinions with regard to reporting and method of measuring margin clearance in VSCC specimens. Given the need for uniformity and the lack of guidance in the literature, we initiated an online survey in order to deliver a consensus-based definition of peripheral surgical margins in VSCC resections. The survey included questions and representative diagrams of peripheral margin measurements. In total, 57 pathologists participated in this survey. On the basis of consensus results, we propose to define MPSM in VSCC as the minimum distance from the peripheral edge of the invasive tumor nests toward the inked peripheral surgical margin reported in millimeters. This MPSM measurement should run through tissue and preferably be measured in a straight line. Along with MPSM, other relevant measurements such as depth of invasion or tumor thickness and distance to deep margins should be reported. This manuscript provides guidance to the practicing pathologist in measuring MPSM in VSCC resection specimens, in order to promote uniformity in measuring and reporting.
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Carcinoma de Células Escamosas/patologia , Neoplasias Vulvares/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Ginecologia , Humanos , Margens de Excisão , Patologistas , Inquéritos e Questionários , Neoplasias Vulvares/cirurgiaRESUMO
The aim of this study was to provide a comprehensive review of the current data surrounding an intrahepatic persistent right umbilical vein in the fetus, including associated anomalies and outcomes, and to assist practitioners in counseling and management of affected pregnancies. We performed a MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Northern Light database search for articles reporting outcomes on prenatally diagnosed cases of a persistent right umbilical vein. Each article was independently reviewed for eligibility by the investigators. Thereafter, the data were extracted and validated independently by 3 investigators. A total of 322 articles were retrieved, and 16 were included in this systematic review. The overall prevalence of an intrahepatic persistent right umbilical vein was found to be 212 per 166,548 (0.13%). Of the 240 cases of an intrahepatic persistent right umbilical vein identified, 183 (76.3%) were isolated. The remaining cases had a coexisting abnormality, including 19 (7.9%) cardiac, 9 (3.8%) central nervous system, 15 (6.3%) genitourinary, 3 (1.3%) genetic, and 17 (7%) placental/cord (predominantly a single umbilical artery). In summary, a persistent right umbilical vein is commonly an isolated finding but may be associated with a coexisting cardiac defect in 8% of cases. Therefore, consideration should be given to fetal echocardiography in cases of a persistent right umbilical vein.
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Veia Porta/anormalidades , Ultrassonografia/estatística & dados numéricos , Veias Umbilicais/anormalidades , Veias Umbilicais/diagnóstico por imagem , Malformações Vasculares/diagnóstico por imagem , Malformações Vasculares/epidemiologia , Feminino , Humanos , Masculino , Veia Porta/diagnóstico por imagem , Prevalência , Fatores de RiscoRESUMO
The principal nature-based solution for offsetting relative sea-level rise in the Ganges-Brahmaputra delta is the unabated delivery, dispersal, and deposition of the rivers' ~1 billion-tonne annual sediment load. Recent hydrological transport modeling suggests that strengthening monsoon precipitation in the 21st century could increase this sediment delivery 34-60%; yet other studies demonstrate that sediment could decline 15-80% if planned dams and river diversions are fully implemented. We validate these modeled ranges by developing a comprehensive field-based sediment budget that quantifies the supply of Ganges-Brahmaputra river sediment under varying Holocene climate conditions. Our data reveal natural responses in sediment supply comparable to previously modeled results and suggest that increased sediment delivery may be capable of offsetting accelerated sea-level rise. This prospect for a naturally sustained Ganges-Brahmaputra delta presents possibilities beyond the dystopian future often posed for this system, but the implementation of currently proposed dams and diversions would preclude such opportunities.
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A new variant of SARS-CoV-2 (Lineage B.1.1.7) was identified in the UK in December 2020 which was associated with higher transmissibility of COVID-19. The AusDiagnostics SARS-CoV-2, Influenza and RSV 8-well assay is used at sixteen UK hospitals and detects part of the ORF8 gene (together with a segment from the ORF1a gene). The objective of this study was to determine if the recently identified mutation in ORF8 (G28048T) in the B.1.1.7. lineage could be used to identify the new variant quickly in clinical cases with PCR positive results. The melt data from SARS-CoV-2 positives from two hospitals (October through December 2020) were reviewed, and distribution over time and location was evaluated. A low melt variant of the ORF8 amplicon started to appear in samples from Guy's and St. Thomas' NHS Trust, London, at the start of November, and grew as a proportion of the total positives during the subsequent two months. These low melt variants were very rare during the same period at the Northern Care Alliance, Greater Manchester, North West of UK. It was confirmed that these carried the G28048T mutation. The geographic and temporal distribution of the low melt amplicons makes it very likely that these are lineage B.1.1.7 strains. The melt temperature of this amplicon could be used to discriminate between the original and new variants in advance of the full sequencing of the isolate. However, the appearance of other mutations in the same amplicon means that this approach would be of diminishing value over time.
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The emergence of variants of SARS-CoV-2 has created challenges for the testing infrastructure. Although large-scale genome sequencing of SARS-CoV-2 has facilitated hospital and public health responses, access to sequencing facilities globally is variable and turnaround times can be significant, so there is a requirement for rapid and cost-effective alternatives. Applying a polymerase chain reaction (PCR)-based single nucleotide polymorphism (SNP) approach enables rapid (<4 h) identification of SARS-CoV-2 lineages from nucleic acid extracts, through the presence or absence of a panel of defined of genomic polymorphisms. For example, the B.1.1.7 lineage ("UK", "Alpha", or "Kent" variant) is characterised by 23 mutations compared to the reference strain, and the most biologically significant of these are found in the S gene. We have developed a SARS-CoV-2 typing assay focused on five positions in the S gene (HV69/70, N501, K417, E484 and P681). This configuration can identify a range of variants, including all the "Variants of Concern" currently designated by national and international public health bodies. The panel has been evaluated using a range of clinical isolates and standardised control materials at four UK hospitals and shows excellent concordance with the known lineage information derived from full sequence analysis. The assay has a turnaround time of about three hours for a set of up to 24 samples and has been utilised to identify emerging variants in a clinical setting.
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Teste de Ácido Nucleico para COVID-19/métodos , COVID-19/diagnóstico , Reação em Cadeia da Polimerase Multiplex/métodos , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Genoma Viral/genética , Humanos , Técnicas de Amplificação de Ácido Nucleico/métodos , Polimorfismo de Nucleotídeo Único/genética , Sensibilidade e Especificidade , Glicoproteína da Espícula de Coronavírus/genética , Sequenciamento Completo do Genoma/métodosRESUMO
Models of fluid flow are used to improve the efficiency of oil and gas extraction and to estimate the storage and leakage of carbon dioxide in geologic reservoirs. Therefore, a quantitative understanding of key parameters of rock-fluid interactions, such as contact angles, wetting, and the rate of spontaneous imbibition, is necessary if these models are to predict reservoir behavior accurately. In this study, aqueous fluid imbibition rates were measured in fractures in samples of the Eagle Ford Shale using neutron imaging. Several liquids, including pure water and aqueous solutions containing sodium bicarbonate and sodium chloride, were used to determine the impact of solution chemistry on uptake rates. Uptake rate analysis provided dynamic contact angles for the Eagle Ford Shale that ranged from 51 to 90° using the Schwiebert-Leong equation, suggesting moderately hydrophilic mineralogy. When corrected for hydrostatic pressure, the average contact angle was calculated as 76 ± 7°, with higher values at the fracture inlet. Differences in imbibition arising from differing fracture widths, physical liquid properties, and wetting front height were investigated. For example, bicarbonate-contacted samples had average contact angles that varied between 62 ± 10° and â¼84 ± 6° as the fluid rose in the column, likely reflecting a convergence-divergence structure within the fracture. Secondary imbibitions into the same samples showed a much more rapid uptake for water and sodium chloride solutions that suggested alteration of the clay in contact with the solution producing a water-wet environment. The same effect was not observed for sodium bicarbonate, which suggested that the bicarbonate ion prevented shale hydration. This study demonstrates how the imbibition rate measured by neutron imaging can be used to determine contact angles for solutions in contact with shale or other materials and that wetting properties can vary on a relatively fine scale during imbibition, requiring detailed descriptions of wetting for accurate reservoir modeling.
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The identification and hit-to-lead exploration of a novel, potent and selective series of histamine H(4) receptor inverse agonists is described. The initial hit, 3A (IC(50) 19 nM) was identified by means of a ligand-based virtual screening approach. Subsequent medicinal chemistry exploration yielded 18I which possessed increased potency (R-enantiomer IC(50) 1 nM) as well as enhanced microsomal stability.
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Antagonistas dos Receptores Histamínicos/farmacologia , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Animais , Disponibilidade Biológica , Descoberta de Drogas , Antagonistas dos Receptores Histamínicos/química , Antagonistas dos Receptores Histamínicos/farmacocinética , Concentração Inibidora 50 , Macaca fascicularis , Ratos , Receptores Histamínicos , Receptores Histamínicos H4 , EstereoisomerismoRESUMO
Objective The objective of this study was to estimate the impact of multidisciplinary (Multi-D) perinatal care conference (PCC) implementation in the private practice setting. Methods After the initial 12-month period following implementation of the monthly PCC by private maternal-fetal medicine and neonatology practitioners, conference attendees were asked to completed a modified version of the Attitudes Toward Health Care Teams Scale, involving 19 questions assessing their attitudes and opinions toward Multi-D team care on a five-point Likert's scale. Results Of the 51 average attendees to the PCC, 82.3% completed the survey. A majority of respondents agreed that Multi-D team care resulted in improved care for patients and family, was not overly complex to coordinate, and resulted in significant job satisfaction and improved medical knowledge. Conclusion Multi-D care is an effective approach to the complicated needs of maternal-fetal medicine patients which may lead to improved patient and family outcomes, high provider satisfaction, and can easily be implemented and utilized within a private practice or community hospital setting.
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Objective Morbidly adherent placentation is associated with increased maternal morbidity and mortality. Recently, there has been mounting evidence supporting the benefits of a standardized multidisciplinary approach at tertiary teaching hospitals. Our objective was to estimate the impact of the implementation of a similar program at a high-volume private community hospital. Study Design In this retrospective cohort study, we evaluated maternal outcomes in all cases of histopathologically confirmed morbidly adherent placentation since the initiation of our multidisciplinary program (2012-2016). Our data were compared with the previously published outcomes of two large cohorts from tertiary teaching hospitals in Utah and Texas. Results In the 28 cases included for evaluation, our group's median estimated blood loss, median packed red blood cells transfused, median anesthesia time, median length of stay, or rates of maternal morbidity did not statistically differ from the published data in Utah or Texas. Conclusion Our data demonstrate the feasibility and utility of a multidisciplinary morbidly adherent placentation program in the private practice/community hospital setting with outcomes similar to those at tertiary teaching hospitals. Implementation of such program may prove beneficial in remote centers, where various factors may prohibit patient travel to a larger center.
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AIM: Maternal corticosteroid administration in pregnancy is known to enhance fetal lung maturity in at risk fetuses. The aim of this study was to test the hypothesis that corticosteroid therapy alters fetal pulmonary blood flow in pregnancies at risk for preterm birth (PTB). MATERIAL AND METHODS: We prospectively evaluated main fetal pulmonary artery (MPA) blood flow in pregnant women at risk for PTB and treated with corticosteroids (betamethasone), compared to an uncomplicated cohort without steroid therapy. The Doppler indices of interest included Peak Systolic Velocity (PSV), Resistive Index (RI), Pulsatility Index (PI), Systolic/Diastolic ratio (S/D ratio), Acceleration Time (AT), and Acceleration Time/Ejection Time Ratio (AT/ET ratio), with the latter serving as the primary outcomes due to its stability irrespective of gestational age. RESULTS: When compared with controls, fetuses treated with corticosteroids demonstrated significantly decreased pulmonary artery acceleration time (median: 28.89 (22.22-51.11) vs. 33.33 (22.20-57.00), p=0.006), while all other indices remained similar. We found no difference in pulmonary blood flow between fetuses who developed respiratory distress syndrome (RDS) and those that did not (31.56 +/- 6.842 vs. 32.36 +/- 7.265, p= 0.76). CONCLUSION: Our data demonstrate altered fetal pulmonary blood flow with corticosteroid therapy, possibly due to increased arterial elastance brought on by medication effect, which leads to the decreased acceleration time or possible gestational age affect. Contrary to a recent report, we did not observe any Doppler differences in fetuses with RDS, which underscores the need for further examination of this proposed association.
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Corticosteroides/farmacologia , Feto/efeitos dos fármacos , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodos , Adulto , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Feminino , Idade Gestacional , Humanos , Gravidez , Estudos Prospectivos , Artéria Pulmonar/embriologia , Ultrassonografia DopplerRESUMO
PURPOSE: Metallothionein, a low molecular weight intracellular protein, binds mitomycin with high affinity protecting the tumor DNA. We prospectively studied the relationship of metallothionein expression in bladder transitional cell carcinoma and resistance to intravesical mitomycin. MATERIALS AND METHODS: A series of 45 consecutive patients with superficial transitional cell carcinoma treated with intravesical mitomycin were studied. Resected tumor tissues were stained with metallothionein monoclonal antibody E9. Two pathologists scored staining intensity and distribution. All patients were followed with regular flexible cystoscopy. RESULTS: Median patient age was 73 years (range 44 to 89). Tumor grade was 1 to 3 in 6, 33 and 6 cases, respectively. In 20 patients (44.44%) tumor recurred after mitomycin therapy. Median cytoplasmic staining scores for recurrent and nonrecurrent tumors were 5 (range 0 to 61) and 0 (0 to 14), respectively. Median nuclear staining scores for recurrent and nonrecurrent tumors were 3 (range 0 to 56) and 0 (0 to 11), respectively. Median followup of patients without recurrence was 18 months (range 12 to 36). Nuclear and cytoplasmic staining scores were significantly higher in recurrent than in nonrecurrent tumors. There was no significant relationship of metallothionein expression with tumor grade. CONCLUSIONS: Over expression of metallothionein predicts the resistance of bladder transitional cell carcinoma to intravesical mitomycin therapy.