Accurately diagnosing indeterminate biliary strictures is challenging but important for patient prognostication and further management. Biopsy sampling under direct cholangioscopic vision might be ...superior to standard ERCP techniques such as brushing or biopsy sampling. Our aim was to investigate whether digital single-operator cholangioscopy (DSOC) compared with standard ERCP workup improves the diagnostic yield in patients with indeterminate biliary strictures.
Patients with an indeterminate biliary stricture on the basis of MRCP were randomized to standard ERCP visualization with tissue brushing (control arm CA) or DSOC visualization and DSOC-guided biopsy sampling (study arm SA). This was a prospective, international, multicenter trial with a procedure-blinded pathologist.
The first sample sensitivity of DSOC-guided biopsy samples was significantly higher than ERCP-guided brushing (SA 68.2% vs CA 21.4%, P < .01). The sensitivity of visualization (SA 95.5% vs CA 66.7%, P = .02) and overall accuracy (SA 87.1% vs CA 65.5%, P = .05) were significantly higher in the SA compared with the CA, whereas specificity, positive predictive value, and negative predictive value showed no significant difference. Adverse events were equally low in both arms.
DSOC-guided biopsy sampling was shown to be safe and effective with a higher sensitivity compared with standard ERCP techniques in the visual and histopathologic diagnosis of indeterminate biliary strictures. (Clinical trial registration number: NCT 03140007.)
Thermo-electro-mechanical vibration of piezoelectric cylindrical nanoshells is studied using the nonlocal theory and Love’s thin shell theory. The governing equations and boundary conditions are ...derived using Hamilton’s principle. An analytical solution is first given for the simply supported piezoelectric nanoshell by representing displacement components in the double Fourier series. Then, the differential quadrature (DQ) method is employed to obtain numerical solutions of piezoelectric nanoshells under various boundary conditions. The influence of the nonlocal parameter, temperature rise, external electric voltage, radius-to-thickness ratio and length-to-radius ratio on natural frequencies of piezoelectric nanoshells are discussed in detail. It is found that the nonlocal effect and thermoelectric loading have a significant effect on natural frequencies of piezoelectric nanoshells.
Soil–bentonite slurry-trench cutoff walls using backfill consisting of on-site sandy soil and Na-bentonite are extensively used as engineering barriers for the purpose of achieving relatively low ...hydraulic conductivity. The amendments such as zeolite to backfill are considered to improve the contaminant sorptive capacity. At some sites, local clayey soil, Ca-bentonite and natural zeolite may be available for an alternate backfill. However, studies on the workability (in terms of slump), compressibility and hydraulic conductivity of such zeolite-amended clayey soil/Ca-bentonite backfills for the cutoff walls are very limited. This paper presents a comprehensive laboratory investigation on the workability, compressibility, and hydraulic conductivity of fine-grained zeolite-amended clayey soil/Ca-bentonite backfills using several series of slump and oedometer tests. Kaolin is used as the model clayey soil, and it is amended with various amounts of Ca-bentonite (7.8–8.4%) and zeolite (10–40%) to prepare zeolite-amended kaolin–bentonite backfills. The test results are compared with previous studies on zeolite-amended sandy soil/Na-bentonite backfills as well as compacted zeolite–bentonite liners to assess the effects of zeolite content and zeolite grain-size on the compressibility and hydraulic conductivity. The results indicate that the water content required to achieve a target slump (100–150mm) for the backfills increases with increasing zeolite content. Liquid limit can be a useful index for a preliminary estimation of the water content required to achieve the target slump for the backfills presented in this study and zeolite-amended sandy soil/Na-bentonite backfills reported in previous studies. The results reveal that the hydraulic conductivity of the zeolite-amended clayey soil/Ca-bentonite backfills with void ratio ranging from 0.54 to 1.45 is generally lower than the typical regulatory limit (10−9m/s). The addition of fine-grained zeolite has insignificant influence on the compressibility and hydraulic conductivity of both clayey soil/Ca-bentonite and sandy soil/Na-bentonite backfills. A proposed empirical method based on the framework of Kozeny–Carman equation can predict the hydraulic conductivity of zeolite-amended clayey soil/Ca-bentonite backfills values within the range of 1/3 to 3 times those calculated from the oedometer tests. The proposed method is also shown to estimate the hydraulic conductivity of the compacted zeolite–bentonite liners from previous studies with reasonable accuracy. Additional research is recommended to evaluate the proposed zeolite-amended backfill using tap water and also by direct measurement of hydraulic conductivity using falling-head or constant-head testing method.
•Liquid limit can be used to preliminarily estimate workability.•Bentonite content critically controls compressibility and hydraulic conductivity.•Addition of fine-grained zeolite insignificantly affects hydraulic conductivity.•Empirical method well predicts hydraulic conductivity.
Siderophores scavenges Fe⁺³ from the vicinity of the roots of plants, and thus limit the amount of iron required for the growth of pathogens such as Fusarium oxysporum, Pythium ultimum, and Fusarium ...udum, which cause wilt and root rot disease in crops. The ability of Pseudomonas to grow and to produce siderophore depends upon the iron content, pH, and temperature. Maximum yield of siderophore of 130 μM was observed at pH 7.0 ± 0.2 and temperature of 30 °C at 30 h. The threshold level of iron was 50 μM, which increases up to 150 μM, favoring growth but drastically affecting the production of siderophore by Pseudomonas aeruginosa JAS-25. The seeds of agricultural crops like Cicer arietinum (chick pea), Cajanus cajan (pigeon pea), and Arachis hypogaea (ground nut) were treated with P. aeruginosa JAS-25, which enhanced the seed germination, root length, shoot length, and dry weight of chick pea, pigeon pea, and ground nut plants under pot studies. The efficient growth of the plants was not only due to the biocontrol activity of the siderophore produced by P. aeruginosa JAS-25 but also may be by the production of indole acetic acid (IAA), which influences the growth of the plants as phytohormones.
Previous studies have shown that clayey soil admixed with Ca-bentonite can be considered as an alternative backfill for slurry-trench cutoff walls. However, the effects of contaminant exposure on the ...engineering properties of the clayey soil/Ca-bentonite backfills, such as compressibility and hydraulic conductivity, have not been investigated. This study presents several series of oedometer tests conducted to evaluate the compressibility and hydraulic conductivity of clayey soil/Ca-bentonite backfills exposed to different levels of lead (Pb) contamination. Kaolin is used as the base clayey soil, and it is amended with Ca-bentonite at three content levels (5, 10 and 15% by dry weight) to prepare the backfill samples. Pb is a representative metal contaminant commonly found at contaminated sites. The backfills are prepared by thoroughly mixing the kaolin–bentonite mixture with Pb concentrations of 60, 120 and 600mmol/L. The results reveal that the level of Pb concentration and bentonite content are the critical factors that affect the compressibility of the backfill. The ratio of the compression index of the Pb-contaminated backfill to that of the clean backfill decreases with an increase in the Pb concentration and bentonite content. The void ratio at an effective vertical compression stress of 1kPa is a useful characteristic parameter to correlate with the compression index for all the backfills tested here. The Pb-contaminated backfills exhibit a maximum fifty-fold increase in hydraulic conductivity when compared to clean backfills. The hydraulic conductivity of the clean backfills and those contaminated at low concentration of Pb (60mmol/L) is generally less than the typical regulatory limit of 10−9m/s; whereas the hydraulic conductivity exceeds the regulatory limit when the Pb concentration is higher than 120mmol/L. The ratio of hydraulic conductivity for Pb-contaminated backfills to that for clean backfill decreases with an increase in the effective vertical compression stress. This indicates that under relatively higher effective vertical compression stress conditions the detrimental effect of Pb on hydraulic conductivity can be insignificant. The hydraulic conductivity of the Pb-contaminated backfills decreases slightly when there is an increase in the bentonite content for a given Pb concentration, while the hydraulic conductivity ratio increases significantly with a rise in the bentonite content. A proposed empirical method is assessed to predict the hydraulic conductivity of Pb-contaminated clayey soil/Ca-bentonite backfills as well as clean ones subjected to vertical compressive stress lower than 1600kPa. Using this method, the predicted hydraulic conductivity values fall in the range of 1/3 to 3 times those obtained from the oedometer tests.
•Pb-contamination affects behavior of clayey soil/Ca-bentonite backfill considerably.•Compression index decreases with increasing Pb concentration.•Hydraulic conductivity significantly increases with increasing Pb concentration.•Empirical methods well predict hydraulic conductivity.
The human papilloma virus (HPV) type 16 and 18 causes nearly 70% of uterine cervical cancers. Oral administration of live Salmonella typhi Ty21a, expressing major capsid proteins (L1) of HPV 16 and ...18 is a potential choice for immunization in adolescent girls under low resource settings. Present study aimed to assess the nonclinical safety of recombinant S. typhi expressing HPV 16 and 18 (rStHPV) proteins.
The acute toxicity of rStHPV was tested by intranasal single dose administration, of 10 and 50 folds higher than clinical prophylactic dose, in mice and rat followed by monitoring their survival for 14 days. Sub-chronic toxicity was evaluated in rats and rabbits with prophylactic and 5 times (average) to clinical prophylactic dosages on scheduled days (1st, 3rd & 5th day) through oral and intranasal routes. The immune/allergic response of rStHPV was assessed in mice through intranasal and intra-peritoneal routes. Experimental animals were daily monitored for live phase, and clinical chemistry, haematology, immunotoxicology, immunogenic response and histopathological examination of vital organs on 15th, 29th and 93rd days.
No abnormal changes were noticed in live phase activity, clinical chemistry and haematology profile. The gross necropsy, organ weights and histopathology were found to be normal. No immunotoxicity was recorded as evaluated by tier I tests. Allergic immune response, as evaluated with IgE levels was also negative irrespective of test routes. On the other hand, a significant (P < 0.01) increase of anti-HPV IgG levels was noted in mice exposed through intranasal route. Though the pre-terminal mortality was noted in mice (6–15%), rats (10%) and rabbits (15%), the autopsy revealed no signs of toxicity related to rStHPV, as the changes neither significant nor dose dependent; and even noted in vehicle control also.
The study results suggested ‘no observable adverse effects’ of rStHPV even at higher dosages (5, 10 & 50 folds) than intended clinical dose. A significant increase of anti-HPV specific IgG suggests the immunogenicity of vaccine. The innovative approach of current study is nonclinical toxicology evaluation of vaccine through intra-nasal route, an alternate route apart from stipulated regulatory guidelines.
Chimeric Antigen Receptor (CAR) T-cells have emerged as a powerful immunotherapy for various forms of cancer and show promise in treating HIV-1 infection. However, significant limitations are ...persistence and whether peripheral T cell-based products can respond to malignant or infected cells that may reappear months or years after treatment remains unclear. Hematopoietic Stem/Progenitor Cells (HSPCs) are capable of long-term engraftment and have the potential to overcome these limitations. Here, we report the use of a protective CD4 chimeric antigen receptor (C46CD4CAR) to redirect HSPC-derived T-cells against simian/human immunodeficiency virus (SHIV) infection in pigtail macaques. CAR-containing cells persisted for more than 2 years without any measurable toxicity and were capable of multilineage engraftment. Combination antiretroviral therapy (cART) treatment followed by cART withdrawal resulted in lower viral rebound in CAR animals relative to controls, and demonstrated an immune memory-like response. We found CAR-expressing cells in multiple lymphoid tissues, decreased tissue-associated SHIV RNA levels, and substantially higher CD4/CD8 ratios in the gut as compared to controls. These results show that HSPC-derived CAR T-cells are capable of long-term engraftment and immune surveillance. This study demonstrates for the first time the safety and feasibility of HSPC-based CAR therapy in a large animal preclinical model.
Soil-bentonite vertical cutoff walls, consisting of a sandy soil mixed with Na-bentonite as backfill, are used extensively as engineered barriers for contaminant containment. However, suitable sandy ...soil and Na-bentonite may not be available at some sites. Consequently, locally available clayey soil and Ca-bentonite may be considered as an alternative backfill. The use of clayey soil/Ca-bentonite backfill may be advantageous to achieve relatively low hydraulic conductivity, which has equivalent performance as that of conventional sandy soil/Na-bentonite backfills. However, studies on the compressibility and hydraulic conductivity of these clayey soil-bentonite backfills are very limited. This paper presents a comprehensive laboratory investigation on the compressibility and hydraulic conductivity of clayey soil/Ca-bentonite backfill through a series of oedometer tests. Kaolin is used as the control clayey soil and it is amended with different contents of Ca-bentonite, 0 (kaolin alone), 5, 10, and 15% (by dry weight basis), to prepare the clayey soil/Ca-bentonite backfills. The initial water contents for the backfills are selected to be 0.75, 1.0, 1.25, and 1.50 times their corresponding liquid limits. The results reveal that the backfills exhibit a noticeable inverse 'S' shaped e-log( sigma ') compression curves attributed to the existence of the remolded yield stress ( sigma ' sub(yr)). The compressibility, in terms of sigma ' sub(yr) and the compression index (C sub(c)), is significantly affected by the initial water content and bentonite content. The void ratio at an effective vertical compression stress of 1 kPa (denoted as e sub(1)) is a useful characteristic parameter to uniquely correlate with C sub(c) for the clayey soil/Ca-bentonite backfills in this study as well as for sandy soil/Na-bentonite and sandy soil-clay backfills that are reported in previous published studies. Unique relationships are also found between the sigma ' sub(yr), initial void ratio (e sub(0)), e sub(1), and the void ratio at liquid limit (e sub(L)). The hydraulic conductivity of the clayey soil/Ca-bentonite backfills is significantly reduced by the bentonite content; generally to less than 10 super(- 9) m/s. An empirical method based on the framework of Kozeny-Carman equation is proposed to predict the hydraulic conductivity of the clayey soil/Ca-bentonite backfills, and the predicted hydraulic conductivity values using these methods are found to fall in the range of 1/3 to 3 times those obtained from the oedometer tests. The proposed method is shown to estimate the hydraulic conductivity for both the clayey soil/Ca-bentonite backfills in this study and the sandy soil-bentonite backfills from published study with reasonable accuracy. Additional research is warranted to prepare the backfills to simulate typical field practice (e.g., use of tap water) and at workable initial water contents (based on the slump testing).
Agricultural field experiments are costly and time-consuming, and often struggling to capture spatial and temporal variability. Mechanistic crop growth models offer a solution to understand intricate ...crop-soil-weather system, aiding farm-level management decisions throughout the growing season. The objective of this study was to calibrate and the Crop Environment Resource Synthesis CERES-Maize (DSSAT v 4.8) model to simulate crop growth, yield, and nitrogen dynamics in a long-term conservation agriculture (CA) based maize system. The model was also used to investigate the relationship between, temperature, nitrate and ammoniacal concentration in soil, and nitrogen uptake by the crop. Additionally, the study explored the impact of contrasting tillage practices and fertilizer nitrogen management options on maize yields. Using field data from 2019 and 2020, the DSSAT-CERES-Maize model was calibrated for plant growth stages, leaf area index-LAI, biomass, and yield. Data from 2021 were used to evaluate the model's performance. The treatments consisted of four nitrogen management options, viz., N0 (without nitrogen), N150 (150 kg N/ha through urea), GS (Green seeker-based urea application) and USG (urea super granules @150kg N/ha) in two contrasting tillage systems, i.e., CA-based zero tillage-ZT and conventional tillage-CT. The model accurately simulated maize cultivar's anthesis and physiological maturity, with observed value falling within 5% of the model's predictions range. LAI predictions by the model aligned well with measured values (RMSE 0.57 and nRMSE 10.33%), with a 14.6% prediction error at 60 days. The simulated grain yields generally matched with measured values (with prediction error ranging from 0 to 3%), except for plots without nitrogen application, where the model overestimated yields by 9-16%. The study also demonstrated the model's ability to accurately capture soil nitrate-N levels (RMSE 12.63 kg/ha and nRMSE 12.84%). The study concludes that the DSSAT-CERES-Maize model accurately assessed the impacts of tillage and nitrogen management practices on maize crop's growth, yield, and soil nitrogen dynamics. By providing reliable simulations during the growing season, this modelling approach can facilitate better planning and more efficient resource management. Future research should focus on expanding the model's capabilities and improving its predictions further.
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