•Numerical and experimental investigations are done using reverse NACA profile ribs.•Optimum results are found with airfoil shaped ribs having chord length of 15 mm.•Nusselt number increased by ...98–193% and friction factor increased by 55–65%.•Maximum Nusselt number and THPP were found to be 104.45 and 2.53 respectively.•Empirical correlations have predicted Nu and f within ±3% of experimental values.
The solar air heater is subjected to a low convective heat transfer coefficient on account of the formation of the laminar sub-layer between the absorber plate and flowing air. To increase the heat transfer coefficient, the laminar sub-layer can be interrupted with the use of artificial roughness (turbulator) on the absorber plate. In the present analysis, the effects of novel type of roughness element in the form of NACA 0040 profile ribs in the reverse position are studied on the performance of the solar air heater. The effects of relative roughness pitch (P/e) and relative roughness height (e/D) were studied for the Reynolds number (Re) ranging from 6000 to 18,000. Among the various roughness parameters, NACA 0040 profile ribs provided in the reverse direction with P/e as 5 and e/D as 0.065 was found to be the optimum. The thermo-hydraulic performance parameter for this case was found to be 2.53 at a Reynolds number of 6000. The experimental results validated the numerical results, and the maximum deviation was found to be 4.84%. An empirical correlation was developed for prediction of Nu and f in terms of Re and e/D and found to conform within ±3% of the corresponding experimental values.
The childhood brain tumor, medulloblastoma, includes four subtypes with very different prognoses. Here, we show that paracrine signals driven by mutant β-catenin in WNT-medulloblastoma, an ...essentially curable form of the disease, induce an aberrant fenestrated vasculature that permits the accumulation of high levels of intra-tumoral chemotherapy and a robust therapeutic response. In contrast, SHH-medulloblastoma, a less curable disease subtype, contains an intact blood brain barrier, rendering this tumor impermeable and resistant to chemotherapy. The medulloblastoma-endothelial cell paracrine axis can be manipulated in vivo, altering chemotherapy permeability and clinical response. Thus, medulloblastoma genotype dictates tumor vessel phenotype, explaining in part the disparate prognoses among medulloblastoma subtypes and suggesting an approach to enhance the chemoresponsiveness of other brain tumors.
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•WNT-medulloblastoma but not other disease subtypes lack a blood brain barrier (BBB)•WNT-medulloblastoma secreted WNT antagonists block BBB formation•BBB function dictates chemotherapy exposure and response among medulloblastomas•The BBB can be manipulated in medulloblastoma by altering tumor vessel signaling
Phoenix et al. show that medulloblastoma genotype dictates tumor vessel phenotype, partially explaining disparate prognoses among subtypes. WNT-medulloblastoma paracrine signals block endothelial WNT signaling, and manipulation of the paracrine axis can alter chemotherapy permeability and response in vivo.
In this work, we demonstrate a cost-effective, scalable, and rapid technique to fabricate a robust, high-performance on-chip positive magnetophoretic system. The system incorporates a thick patterned ...permanent magnet and microfluidic channel on a single polymethyl methacrylate (PMMA) substrate for on-chip manipulation of magnetic particles (MPs). Using the suitable patterning of the magnet, a spatially varying magnetic force is exerted onto the MPs in the channel, which is pertinent for capturing the MPs at specific locations. The device geometry is optimized using FEM simulations to prevent any blockage in the channel due to the accumulation of the MPs and ease the fabrication process. The <inline-formula> <tex-math notation="LaTeX">\sim</tex-math> </inline-formula>1.5-fold enhancement in the trapping efficiency is observed upon lowering the flow rate from 15 <inline-formula> <tex-math notation="LaTeX">\mu </tex-math> </inline-formula>l/min to 9 <inline-formula> <tex-math notation="LaTeX">\mu </tex-math> </inline-formula>l/min, leading to 94.5% trapping efficiency at a lower flow rate of 9 <inline-formula> <tex-math notation="LaTeX">\mu </tex-math> </inline-formula>l/min. 2022-0173
Drought is characterized by a prolonged and abnormal lack of moisture, often stemming from insufficient or uneven distribution of precipitation, resulting in water shortages in streams or reservoirs, ...with detrimental impacts on both natural and socioeconomic systems. The paper focuses on the climatic drought patterns within the Right Bank Main Canal Command Area of Gujarat’s Dharoi Reservoir. To evaluate drought conditions, the study employs several indices including the Standardized Precipitation Index (SPI)and Normalized Difference Vegetation Index (NDVI). Daily rainfall data, obtained from IMD gridded data and extracted using ArcGIS software, is utilized to calculate SPI values at a three-month time scale. NDVI is determined using Landsat-8 OLI data spanning from 2013 to 2022 to analyze changes in agricultural vegetation. Comparisons among NDVI and SPI reveal that the year 2018 experienced significant rainfall deficits across the region, leading to severe water scarcity. This shortage impacted agricultural practices, evident in reduced crop cultivation areas as indicated by NDVI results and validated using the crop yield data for the time series. Specifically, the NDVI analysis highlights that 33.5% of the RBMC command area exhibited signs of dryness, with an additional 64.5% showing moderate dryness. The study endeavors to pinpoint drought-affected regions utilizing precipitation data, reservoir storage information, and remote sensing methodologies.
•Novel LC–MS/MS methods for the quantitation of ribociclib in mouse plasma and Ringer's solution were developed and validated.•Mouse plasma samples were extracted using solid phase extraction method, ...no extraction was required for the Ringer’s solution samples.•These methods were successfully applied for the determination of ribociclib concentration in preclinical samples obtained from cerebral microdialysis studies.
LC–MS/MS methods to measure ribociclib in mouse plasma and Ringer’s solution were successfully developed and validated. Reverse phase chromatography was performed with gradient elution using C18 (100A, 50×4.6mm, 3μ) and C8-A (50×2.0mm, 5μ) columns for plasma and Ringer’s samples, respectively. Mouse plasma samples were extracted using solid phase extraction method, whereas no extraction was required for the Ringer’s solution samples. Analytes were detected using positive ion MRM mode. The precursor to product ions (Q1→Q3) selected for ribociclib and d6-ribociclib were (m/z) 435.2→252.1 and 441.2→252.1, respectively. The linear range of quantification of ribociclib was 62.5–10,000ng/ml for plasma method and 0.1–100ng/ml for Ringer’s solution method. The results for the inter-day and intra-day accuracy and precision of quality control samples were within the acceptable range. The lower limit of quantitation (LLOQ) for plasma and Ringer’s samples were 62.5ng/ml (S/N>30) and 0.1ng/ml (S/N>13), respectively, whereas the limit of detection (LOD) was 6.9ng/ml (S/N>7) and 0.05ng/ml (S/N>3), respectively. The developed methods were successfully applied to the analysis of ribociclib in mouse plasma and dialysate samples collected during a cerebral microdialysis study of ribociclib in a non-tumor bearing mouse.
The aim of this study was to determine the prevalence and characteristics of postoperative pain after endodontic microsurgery and to identify potential predictors for severe pain.
One hundred ...seventy-three patients who underwent endodontic microsurgery at a private practice were included in the study. The patients were asked to fill out a questionnaire to assess their postoperative pain levels for 5 days after surgery. The questionnaires were analyzed to record the changes in pain levels over time. The presence and size of preoperative lesions and bone thickness were determined on preoperative cone-beam computed tomographic scans. Statistical analyses were performed to identify predictors for developing severe pain after surgery. A binary logistic regression model was established to predict the occurrence of severe pain.
Severe pain was most prevalent on day 1 (17.3%) and gradually decreased until a small increase on day 5. The average pain level also peaked on day 1 postoperatively and gradually decreased afterward. No significant difference was observed between patients who reported severe pain and those who did not report severe pain regarding tooth position (anterior vs posterior), lesion size, and presence of fenestration. However, sex, age, and bone thickness were all significant predictors of severe postoperative pain, with odds ratios of 2.8, 0.96, and 1.41, respectively.
Severe pain was reported only in a small number of patients after endodontic microsurgery. Younger patients, females, and patients with thicker bone covering the apex are significantly more likely to develop severe pain.
Abstract Introduction The purpose of this retrospective study was to determine the clinical and radiographic outcome of root-end surgery when EndoSequence BC Root Repair (ES-BCRR) was used as the ...root-end filling material and to identify any possible prognostic factors that may have affected the healing outcome. Methods Clinical records and periapical radiographs were collected from patients who had undergone endodontic microsurgery between 2009 and 2013 in a private endodontic office and had a minimum 1-year follow-up. All surgical procedures were performed by a single endodontist. ES-BCRR was used as the root-end filling material in all cases. Outcome was categorized into healed, healing, and non-healing on the basis of clinical and radiographic findings. The healed and healing cases were pooled and considered as success, and non-healing cases were considered failure. For statistical analysis of the prognostic factors, the dependent variable was the dichotomous outcome (ie, success versus failure). Results Ninety-four patients with 113 teeth met the inclusion criteria and were included in the study. The overall success rate was 92.0%. None of the prognostic factors, including age, sex, tooth position, size of periapical radiolucency, presence of a sinus tract, preoperative symptoms, and retreatment previous to surgery, appeared to have any significant effects on the outcome ( P > .05). Conclusions This current study suggests that ES-BCRR is a suitable root-end filling material to be used in endodontic surgery.
Despite significant improvement in outcomes for patients with hematologic malignancies and solid tumors over the past 10 years, patients with primary or metastatic brain tumors continue to have a ...poor prognosis. A primary reason for this is the inability of many chemotherapeutic drugs to penetrate into the brain and brain tumors at concentrations high enough to exert an antitumor effect because of unique barriers and efflux transporters. Several studies have been published recently examining the central nervous system pharmacokinetics of various anticancer drugs in patients with primary and metastatic brain tumors. To summarize recent advances in the field, this review critically presents studies published within the last 9 years examining brain and cerebrospinal fluid penetration of clinically available anticancer agents for patients with central nervous system tumors.
Ceftolozane-tazobactam, a combination of the novel antipseudomonal cephalosporin ceftolozane and the well-established extended-spectrum β-lactamase inhibitor tazobactam, is approved for treating ...complicated urinary tract infections (cUTI) and complicated intra-abdominal infections (cIAI) in adults. To determine doses likely to be safe and efficacious in phase 2 pediatric trials for the same indications, single-dose ceftolozane-tazobactam plasma pharmacokinetic data from a recently completed phase 1 trial in pediatric patients (birth to <18 years old) with proven/suspected Gram-negative bacterial infections, along with pharmacokinetic data from 12 adult studies, were integrated into a population pharmacokinetic (popPK) analysis. Two-compartment linear models with first-order elimination described the concentration-time profiles of ceftolozane and tazobactam in pediatric patients well. Renal function and body weight were identified to be significant predictors of ceftolozane-tazobactam pharmacokinetics. Renal function, as measured by the estimated glomerular filtration rate (eGFR), significantly affected the clearance of both ceftolozane and tazobactam. Body weight significantly affected clearance and the distribution volume, also of both ceftolozane and tazobactam. Patients with infections had a 32.3% lower tazobactam clearance than healthy volunteers. Using the final popPK models, simulations of various dosing regimens were conducted to assess each regimen's plasma exposure and the probability of pharmacokinetic/pharmacodynamic target attainment. Based on these simulations, the following doses are recommended for further clinical evaluation in phase 2 pediatric trials for cUTI and cIAI (in patients with an eGFR of ≥50 ml/min/1.73 m
only): for children ≥12 years old, 1.5 g ceftolozane-tazobactam (1 g ceftolozane with 0.5 g tazobactam), and for neonates/very young infants, infants, and children <12 years old, 20/10 mg/kg of body weight ceftolozane-tazobactam, both via a 1-h intravenous infusion every 8 h.
Purpose
Ribociclib, an orally bioavailable small-molecule CDK4/6 inhibitor is currently undergoing evaluation to treat pediatric central nervous system (CNS) tumors. However, it is crucial that it ...penetrates the brain and tumor. Thus, the objectives of the present study were to derive a clinically relevant mouse dosage for cerebral microdialysis studies, and to characterize ribociclib CNS penetration in non-tumor bearing mice and in mice bearing DIPGx7 (glioma) cortical allograft tumors.
Methods
A plasma pharmacokinetic study of ribociclib (100 mg/kg, orally) was performed in CD1 nude mice bearing glioma cortical allografts to obtain initial plasma pharmacokinetic parameters and to derive D-optimal plasma sampling time-points for microdialysis studies. Using a cerebral microdialysis technique, the extracellular fluid (ECF) disposition of ribociclib was evaluated after a single oral ribociclib dose (100 mg/kg) in non-tumor bearing mice and in mice bearing glioma cortical allografts. A one-compartment plasma model with absorption and ECF compartments were fit to plasma and ECF concentration–time data using a nonlinear mixed effects modeling approach (NONMEM 7.2).
Results
The mean unbound ribociclib plasma exposure (6812 ng/ml*h) was similar to that observed clinically at recommended dosages in adults. The median ribociclib ECF to plasma partition coefficient (
K
p,uu
) in non-tumor bearing and glioma mice was 0.10 and 0.07, respectively, and was not statistically different (
t
test,
p
= 0.19).
Conclusions
The CNS penetration observed was encouraging enough to move ribociclib forward with preclinical efficacy studies in models of pediatric brain tumors.
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