The implications of the shear-free condition on the instability range of an anisotropic fluid in
f
(
R
,
T
) are studied in this manuscript. A viable
f
(
R
,
T
) model is chosen to arrive at ...stability criterion, where
R
is Ricci scalar and
T
is the trace of energy-momentum tensor. The evolution of a spherical star is explored by employing a perturbation scheme on the modified field equations and contracted Bianchi identities in
f
(
R
,
T
). The effect of the imposed shear-free condition on the collapse equation and adiabatic index
Γ
is studied in the Newtonian and post-Newtonian regimes.
The theory and practice of unmanned aerial vehicle (UAV) capture and control via Global Positioning System (GPS) signal spoofing are analyzed and demonstrated. The goal of this work is to explore UAV ...vulnerability to deceptive GPS signals. Specifically, this paper (1) establishes the necessary conditions for UAV capture via GPS spoofing, and (2) explores the spoofer's range of possible post‐capture control over the UAV. A UAV is considered captured when a spoofer gains the ability to eventually specify the UAV's position and velocity estimates. During post‐capture control, the spoofer manipulates the true state of the UAV, potentially resulting in the UAV flying far from its flight plan without raising alarms. Both overt and covert spoofing strategies are considered, as distinguished by the spoofer's attempts to evade detection by the target GPS receiver and by the target navigation system's state estimator, which is presumed to have access to non‐GPS navigation sensor data. GPS receiver tracking loops are analyzed and tested to assess the spoofer's capability for covert capture of a mobile target. The coupled dynamics of a UAV and spoofer are analyzed and simulated to explore practical post‐capture control scenarios. A field test demonstrates capture and rudimentary control of a rotorcraft UAV, which results in unrecoverable navigation errors that cause the UAV to crash.
•An anti-tumor protein, p-53, is functionally inactivated in most tumors.•We have examined the effects of pharmacodynamic interaction between Nutlin-3a and aspirin in cancer patients.•The ...mathematical result shows that p-53 protein gets over-activated and starts suppressing other useful growth cells if a high dose of aspirin along with nutlin-3a is administered in a cancer patient.•In order to avoid any harmful effect of such interaction in the activation of p-53 protein, a low dose of aspirin should be administered along with nutlin-3a.
p53, an anti-tumour protein, is significantly inactivated in most tumours. A small molecule of nutlin-3a is used to activate its function by repressing (Mouse double minute 2 homolog) Mdm2 protein which inhibits its activity. In cancer patients, a high risk of drug-drug interactions (DDIs) is observed owing to their multi-dosing prescriptions, which may lead them to harmful effects. In the presented work, we have aimed to investigate the effect of pharmacodynamical interaction between two anti-cancer drugs, nutlin-3a and aspirin in the activation of p53 protein.
We have adapted control system techniques and designed a Proportional-Integral-Derivative (PID) controller. This controller is used to activate p53 protein. A drug interaction parameter is used to incorporate the effect of both drugs. Extensive simulation is performed using two different doses of aspirin, i.e. a low and a high dose of aspirin.
The result shows no harmful effects of pharmacodynamical interaction when a low dose is administered along with nutlin-3a. When a high dose of aspirin is administered it acts as input disturbance and leads to undesirable over-expression of p53 protein. This can further harm other growth cells, thus inducing harmful effects. A comparative analysis is also tabulated with different dosing regimens which shows that a combination of nutlin-3a and a low dose of aspirin provides better results than a high dose of aspirin.
Overall, the work provides an insight to the activation of p53 protein in cancer patients under the presence of pharmacodynamical interaction and might contribute to the effective management of cancer patients.
The band structures and density of states (DOS) of all the three structural configurations of CsPbBr
3
without spin–orbit coupling (SOC = 0) and with the addition of spin–orbit coupling (SOC ≠ 0) ...effects were calculated, using density functional theory. Upon the inclusion of the spin–orbit coupling, the bandgaps exhibit reductions of 1.27 eV, 1.16 eV and 1.08 eV for the cubic, tetragonal and orthorhombic phases, respectively. These calculations provide a positive split-off energy value of Δ
so
= 1.69 eV for the simple cubic phase. For the lower symmetry phases, the
p
-like fourfold degenerate
Γ
8
v
(
4
)
band has been observed to split to form two bands, in addition to the
Γ
6
v
(
2
)
split-off band. The calculated splitting energies between these bands are found to be in close agreement with previous experimentally measured values. The calculated electronic band structures show that CsPbBr
3
has a negative ‘inversion energy’ (Δ
i
< 0). The magnitude of the inversion energy for the cubic phase is 2.36 eV for SOC = 0, which increased by 0.4–2.76 eV with the addition of the spin–orbit coupling. The arrangement of Bloch levels in the band structure of CsPbBr
3
has been found to resemble that of a typical topological semimetal, but with a nonzero bandgap opening, due to the presence of the inversion asymmetry within its molecular structure.
Large population-based studies examining differences in ICI-associated cardiotoxicity across cancer types and agents are limited. Data of 5518 cancer patients who received at least one cycle of ICIs ...were extracted from a large network of health care organizations. ICI treatment groups were classified by the first ICI agent(s) (ipilimumab, nivolumab, pembrolizumab, cemiplimab, avelumab, atezolizumab, or durvalumab) or its class (PD-1 inhibitors, PD-L1 inhibitors, CTLA4-inhibitors, or their combination (ipilimumab + nivolumab)). Time to first cardiac adverse event (CAE) (arrhythmia, acute myocardial infarction, myocarditis, cardiomyopathy, or pericarditis) developed within one year after ICI initiation was analyzed using a competing-risks regression model adjusting for ICI treatment groups, patient demographic and clinical characteristics, and cancer sites. By month 12, 12.5% developed cardiotoxicity. The most common cardiotoxicity was arrhythmia (9.3%) and 2.1% developed myocarditis. After adjusting for patient characteristics and cancer sites, patients who initiated on monotherapy with ipilimumab (adjusted Hazard Ratio (aHR): 2.00; 95% CI: 1.49−2.70; p < 0.001) or pembrolizumab (aHR: 1.21; 95% CI: 1.01−1.46; p = 0.040) had a higher risk of developing CAEs within one year compared to nivolumab monotherapy. Ipilimumab and pembrolizumab use may increase the risk of cardiotoxicity compared to other agents. Avelumab also estimated a highly elevated risk (aHR: 1.92; 95% CI: 0.85−4.34; p = 0.117) compared to nivolumab and other PD-L1 agents, although the estimate did not reach statistical significance, warranting future studies.
•The PBPK modeling is used in the process of Drug discovery and development.•The comprehensive PBPK model known as a whole body physiologically based pharmacokinetic (WB-PBPK) model is proposed by ...Dedrick and Bischoff in 1968, but did not implement and verified.•The WBPBPK model is developed with the integration of ADME models alongside the reference PBPK model.•The developed WB PBPK model is used to anticipate a systemic exposure of the drug in all compartments of the body.•The validity of the model is confirmed by the comparison of simulations of a model and clinical data of Belinostat, Allopurinol, and Paracetamol.•Preference point of this WB-PBPK model over conventional PBPK models is its prediction of concentrations of drugs as a function of time.
The Physiologically based pharmacokinetic (PBPK) modeling is a supporting tool in drug discovery and improvement. Simulations produced by these models help to save time and aids in examining the effects of different variables on the pharmacokinetics of drugs. For this purpose, Sheila and Peters suggested a PBPK model capable of performing simulations to study a given drug absorption. There is a need to extend this model to the whole body entailing all another process like distribution, metabolism, and elimination, besides absorption. The aim of this scientific study is to hypothesize a WB-PBPK model through integrating absorption, distribution, metabolism, and elimination processes with the existing PBPK model.Absorption, distribution, metabolism, and elimination models are designed, integrated with PBPK model and validated. For validation purposes, clinical records of few drugs are collected from the literature. The developed WB-PBPK model is affirmed by comparing the simulations produced by the model against the searched clinical data. . It is proposed that the WB-PBPK model may be used in pharmaceutical industries to create of the pharmacokinetic profiles of drug candidates for better outcomes, as it is advance PBPK model and creates comprehensive PK profiles for drug ADME in concentration-time plots.
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The purpose of this study was to evaluate the relationship between technical performance and patient outcomes in laparoscopic gastric cancer surgery.
Laparoscopic gastrectomy for cancer is an ...advanced procedure with high rate of postoperative morbidity and mortality. Many variables including patient, disease, and perioperative management factors have been shown to impact postoperative outcomes; however, the role of surgical performance is insufficiently investigated.
A retrospective review was performed for all patients who had undergone laparoscopic gastrectomy for cancer at 3 teaching institutions between 2009 and 2015. Patients with available, unedited video-recording of their procedure were included in the study. Video files were rated for technical performance, using Objective Structured Assessments of Technical Skills (OSATS) and Generic Error Rating Tool instruments. The main outcome variable was major short-term complications. The effect of technical performance on patient outcomes was assessed using logistic regression analysis with backward selection strategy.
Sixty-one patients with available video recordings were included in the study. The overall complication rate was 29.5%. The mean Charlson comorbidity index, type of procedure, and the global OSATS score were included in the final predictive model. Lower performance score (OSATS ≤29) remained an independent predictor for major short-term outcomes (odds ratio 6.49), while adjusting for comorbidities and type of procedure.
Intraoperative technical performance predicts major short-term outcomes in laparoscopic gastrectomy for cancer. Ongoing assessment and enhancement of surgical skills using modern, evidence-based strategies might improve short-term patient outcomes. Future work should focus on developing and studying the effectiveness of such interventions in laparoscopic gastric cancer surgery.
We estimated the number of hospital workers in the United States (US) that might be infected or die during the COVID-19 pandemic based on the data in the early phases of the pandemic.
We calculated ...infection and death rates amongst US hospital workers per 100 COVID-19-related deaths in the general population based on observed numbers in Hubei, China, and Italy. We used Monte Carlo simulations to compute point estimates with 95% confidence intervals for hospital worker (HW) infections in the US based on each of these two scenarios. We also assessed the impact of restricting hospital workers aged ≥ 60 years from performing patient care activities on these estimates.
We estimated that about 53,000 hospital workers in the US could get infected, and 1579 could die due to COVID19. The availability of PPE for high-risk workers alone could reduce this number to about 28,000 infections and 850 deaths. Restricting high-risk hospital workers such as those aged ≥ 60 years from direct patient care could reduce counts to 2,000 healthcare worker infections and 60 deaths.
We estimate that US hospital workers will bear a significant burden of illness due to COVID-19. Making PPE available to all hospital workers and reducing the exposure of hospital workers above the age of 60 could mitigate these risks.
Abstract
Visualization of cutaneous micro-vasculatures is a powerful approach assisting in the diagnosis of skin vascular disorders. These minute structures can be visualized by high-frequency ...ultrasound (HFUS) using ultrafast Doppler imaging. Ultrasound flow phantoms have been used as assessment tools to evaluate the performance of the ultrasound imaging system, however, to optimize the imaging system for visualization of micro-structures, flow phantom with micro-channels is required which are usually difficult to fabricate. Here, we design a simple approach for micro-flow phantom which is easy to fabricate and cast for detection of micro-circulation in superficial micro-structures. The proposed approach features (i) the micro-channels of 200-micron at the depth of 4 mm (ii) casted in the cryogel mixture of Poly-vinyl alcohol (PVA) and (iii) infused at flow speed of 30 mm/s using infusion pump. Visualization of micro-flow channel in power Doppler image obtained by HFUS ultrafast Doppler imaging reveals that the proposed micro-flow phantom could serve as a viable assessment tool for optimizing the system for in-vivo cutaneous micro-vasculature imaging.
Fungal infections in immune-compromised patients are an important cause of mortality and morbidity. Amphotericin B (Amp B) is considered a powerful fungicidal drug but its clinical usage has certain ...limitations when administered intravenously due to its toxicity and poor solubility. In consideration of such challenges, in cutaneous leishmaniasis, the topical application of Amp B can be a safer option in many aspects. Thus, herein, biopolymer of polycaprolactone (PCL) nanoparticles (NPs) were developed with the loading of Amp B by nanoprecipitation for the treatment of topical leishmanial infections. Various parameters, such as concentration of PCL and surfactant Poloxamer 407, were varied in order to optimize the formation of nanoparticles for the loading of Amp B. The optimized formulation exhibited a mean hydrodynamic particle size of 183 nm with a spherical morphology and an encapsulation efficiency of 85%. The applications of various kinetic models reveal that drug release from nanoformulation follows Korsmeyer–Peppas kinetics and has a high diffusion exponent at a physiological pH of 7.4 as well a skin relevant pH = 5.5. The activity of the prepared nanoparticles was also demonstrated in Leishmania infected macrophages. The measured IC50 of the prepared nanoparticle formulation was observed to be significantly lower when compared to control free Amp B and AmBisome® for both L. tropica KWH23 and L. donovani amastigotes in order to demonstrate maximum parasite inhibition. The prepared topical nanoformulations are capable of providing novel options for the treatment of leishmaniasis, which can be possible after in vivo assays as well as the establishment of safety profiles.
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