Half-life Values Research Articles

Dissipation kinetics, risk assessment, and waiting period of spiromesifen on chili fruits using gas chromatography-electron capture detector.

A supervised field trial was designed in Rajasthan Agricultural Research Institute, Durgapura, Jaipur, Rajasthan, to assess the dissipation and persistence of spiromesifen in chili fruits. Spiromesifen (22.9% suspension concentrate) was sprayed two times at an interval of 10 days at the recommended dose (96 g. a.i. ha-1 ) and double the recommended dose (192 g. a.i. ha-1 ) with four replications. Sampling was done according to the planned interval of days after the second spray. Extraction and cleanup were performed using the modified QuEChERS (quick, easy, cheap, effective, rugged, and safe) method and the spiromesifen residue was analyzed by GC-electron capture detector and confirmation performed using GC-MS. The average initial deposit of spiromesifen was 1.207 mg kg-1 and 1.948 mg kg-1 at the recommended and double the recommended dose, respectively. The half-life values of spiromesifen ranged between 2.7 and 3.2 days at the recommended and double the recommended dose. The safe waiting period was calculated for the respective doses and it was concluded that an average of 7 days is safe for picking. The FSSAI (Food Safety and Standards Authority of India) have set the maximum residue limit of 0.1 mg kg-1 for spiromesifen in green chili. The theoretical maximum residue contribution value of spiromesifen was lower than the maximum permissible intake at both the applications on the 0th day. Hence, there will be no adverse effects on human health after consumption of green chilies.

Half-life determination of 111Ag

111Ag is a radionuclide that can be generated by neutron capture on 110Pd and whose decay properties and production feasibility make it a potential therapeutic agent against arthritis. Due to the discrepancies of recent published values of the half-life of 111Ag with previous published works which are not thoroughly documented for detailed experiment procedures and uncertainty budgets evaluation, an independent redetermination of the 111Ag half-life value is required. In this work, a solid 111Ag source was prepared and repeatedly measured in a high purity Germanium (HPGe) detector to determine its half-life. In total, more than fifty measurements were performed over a period of 26.3 days, corresponding to ∼3.5 half-lives of 111Ag. The experimental method and corresponding uncertainty budget are presented. The result of 7.419(15) days is consistent with the recently published value, 7.423(13) days, by Collins et al. and deviates by 0.418% from the currently recommended value 7.45(1) days. A new recommend half-life value of 7.437(7) days was determined utilizing all available experimental values by a power-moderated mean (PMM) method.

Development and validation of LC-MS/MS method for determining the metabolic stability, pharmacokinetics, and dose proportionality of a novel anti-inflammatory cofilin inhibitor

A novel small molecule cofilin inhibitor (SZ-3) has recently become the focus of investigation for targeting neuroinflammation in different neurodegenerative diseases. In the present study, the metabolic stability, blood-brain barrier (BBB) penetration, and tissue concentration of SZ-3 were evaluated to support our future studies. In silico drug metabolism prediction was investigated using the StarDrop WhichP450 module. LC-MS/MS method was developed and validated to quantify the SZ-3 for in-vitro and in-vivo studies. The in-vitro metabolic stability was performed using human liver microsomes (HLMs), and the in-vivo pharmacokinetics were investigated in mice after a single intraperitoneal (IP) injection or oral (P.O.) administration, followed by a collection of blood and brain samples at different time points. The dose-proportionality was also evaluated after a single IP injection of three ascending doses (5, 10, and 25 mg/kg). In-vitro results showed that SZ-3 has a moderate intrinsic clearance (Clint) value of 17.42 ml/min/mg with a half-life (t1/2) value of 39.77 mins, indicative of good bioavailability. In vivo study revealed that SZ-3 was rapidly absorbed, entered the brain, and yielded a good concentration of the unbound drug after IP and oral administration. However, the higher maximum concentration (Cmax) values of IP and P.O. (2244 ng/ml and 1069 ng/g, respectively) revealed that the IP administration led to higher blood and brain concentrations than the P.O. Furthermore, Cmax and area under the curve (AUC) of SZ-3 increased in a dose-proportional manner between the three ascending doses. These results will guide us in optimizing the dosing regimen for future SZ-3 pharmacological studies targeting neuroinflammation.

Murine toxicology and pharmacokinetics of lead next generation galeterone analog, VNPP433-3β

VNPP433-3β (compound 2, (3β-(1H-imidazole-1-yl)-17-(1H-benzimidazole-1-yl)-androsta-5,16-diene), a multitarget anticancer agent has emerged as our lead next generation galeterone analogs (NGGA). Compound 2 is currently in development as potential new therapeutic for prostate and pancreatic cancers. The preliminary toxicity study reveals that the compound 2 was better tolerated by the normal male CD-1 mice than the male Nude mice. The maximum tolerated dose (MTD) in the Nude mice was estimated to be between 25 < 50 mg/kg. After oral dosing of compound 2 to male and female rats, the plasma concentration versus time curves were very consistent between animals and the AUClast increased with dose. Many plasmas concentration versus time curves profiles were nearly flat over 24 hr., suggesting extended absorption from the GI tract. Consequently, reliable values for half-life and AUCinf were not determined. Calculated oral bioavailability (using oral AUClast and excluding the outlier IV animal) ranged from 32 to 47 %. This should be considered a minimum value since the contribution to true AUC beyond 24 hr. is clearly not zero. Clearly, these toxicology and pharmacokinetics parameters pave the way for understanding the anticancer pharmacological actions and provide a meaningful basis for further preclinical development and eventual clinical development.

Acalypha wilkesiana acid extract as a potential green inhibitor for corrosion of mild steel in acidic medium: Thermodynamics and kinetics study

The use of synthetic compounds as corrosion inhibitor is diminishing due to strict environmental regulations and toxic effects of the compounds on human beings and the environment. Consequently, there exists the need to develop a new class of corrosion inhibitors with low toxicity, eco-friendliness and good efficiency. Therefore, this study investigates the inhibitory potential of Acalypha wilkesiana (AWAE) extract on mild steel in 1M HCl using weight loss method. Experiments were performed by varying immersion period, concentration of the inhibitor and temperature. The results obtained showed a decrease in the corrosion rate of mild steel as the extract concentration increases while the inhibition efficiency increases with extract concentration. Effect of temperature on the inhibition efficiency showed an increase in inhibition efficiency with rise in temperature. The adsorption of the inhibitor on the mild steel surface in acid solution was found to obey the Langmuir adsorption isotherm. Calculated thermodynamic parameters revealed that the mechanism of the corrosion inhibition may be due to the chemical adsorption of the phyto-constituents on the surface of mild steel. Kinetic treatment of the data followed a first order reaction and the half-life values of the metal increase with increase in the extract concentration. Preliminary investigation of the phytochemical constituents showed that Acalypha wilkesiana contains tannin, flavonoid, saponin, alkaloid, steroid , terpenoid and some other compounds in trace quantity. FTIR results indicate that AWAE contains O and N atoms in functional groups and aromatic ring which meet the general consideration of a typical corrosion inhibitor.

Analysis of Tc99m MDP Radiopharmaceuticals in the Spinal Areas of Breast Cancer Patients

The aim of this study was to obtain doses in the spine of breast cancer patients. This dose is very important in pharmacy to determine the distribution of drugs in the body's organs, especially the spine. The data of this study came from the results of bone scintigraphy examinations which had known the value of the injection dose and the percentage of absorption in the spine. This research was conducted by simulating the biological half-life values for 3 hours, 4 hours, 5 hours, 6 hours, and 7 hours to find the total half-life which will produce a total decay constant that will be used in calculating spinal dose. The results obtained were the lowest mean dose in the spinal 0.680 ± 0.160 mCi when the decay constant had the highest value (biological half-life 3 hours) and the largest mean dose in the spinal 1.011 ± 0.238 mCi when the decay constant had the lowest value (biological half-life 7 hours). In the spine, the thoracic region is the area with the highest dose because it is located closest to the breast organs (breast cancer) so it will experience the highest damage/metastasis. Then the Tc99m MDP radiopharmaceutical absorbed into the thoracic region will be higher. By simulating the biological half-life, it is hoped that we can find the exact biological half-life for the absorbed dose

On Systematics of Double-Beta Decay Half Lives

Recommended 2β−(2ν) half-lives and their systematics [1, 2] are examined in the framework of a semi-empirical approach. Impacts of nuclear deformation, transition energy, shape coexistence, and forbidden transitions on half-live values were observed. These findings were used to predict T1/2 for 36 isotopes of interest. Current results are compared with available data.

The β-decay of 71Kr: Precise measurement of the half-life

The very proton-rich 71Kr isotope was produced through the in-flight fragmentation of 78Kr on a beryllium target at RIKEN – Nishina Center in order to study its β-decay properties. A stack of double-sided silicon strip detectors, called WAS3ABi, was used as the decay station, where the detection of ion implants, β-decays and β-delayed protons took place. Beta-delayed γ-rays were measured using a system of 84 HPGe detectors, called EURICA, surrounding the decay station. The main goal of the present study was the precise measurement of the half-life of 71Kr, as in the literature there is an almost 10 σ difference between the most precise independent results. Implant–β time correlations, implant–proton time correlations and implant–β–γ time correlations were all used to derive the half-life value, followed by a thorough investigation of systematic uncertainties for each method. As these values were found to be consistent, the weighted average t1/2 = 94.40+19ms is reported as a new half-life value in this work. Furthermore a total of 26 previously unreported γ following the β-decay of 71Kr were also identified in the analysis.

Расчёт фармакокинетических и дозиметрических характеристик Lu-177-ЭДТМФ – потенциального препарата для радионуклидной терапии костных метастазов

Phosphonic acids labeled with beta-emitting radionuclides are promising radiopharmaceutical drugs for palliative therapy of bone metastases. Currently, the possibility of using a new osteotropic compound N,N,N’,N’-ethylenediaminetetrakis (methylene phosphonic acid) with lutetium-177 (177Lu-EDTMP) is being studied. The aim of the work is to develop a compartment mathematical model of the kinetics of 177Lu labeled osteotropic radiopharmaceutical drugs in the body of laboratory animals and calculate their pharmacokinetic and dosimetric characteristics based on it. To assess the stability of 177Lu-EDTMP in vivo, the characteristics of the distribution of free lutetium in the form of 177LuCl3 were also studied. To identify the model parameters and calculate the characteristics of radiopharmaceutical drugs, quantitative data on the bio-distribution of 177Lu-EDTMP and 177LuCl3 in the body of intact Wistar rats were used. A compartment model of kinetics has been developed and two approaches to the identification of its transport constants have been proposed – through the residual functional and using approximation by monoexponential functions. According to pharmacokinetic modeling, it was found that 177Lu-EDTMP is deposited in bone tissues (up to 55% of the administered dose). The calculated value of the apparent volume of distribution of 177Lu-EDTMP is approximately 200 times greater than the volume of blood plasma, the values of biological half-lives from bone tissues are 10-20 times higher than from internal organs. The excretion of 177Lu-EDTMP from the body occurs mainly through renal clearance. Comparative modeling with 177LuCl3 revealed high resistance of 177Lu-EDTMP in vivo. The highest values of absorbed doses are formed in the skeleton and kidneys with minimal radiation load on other internal organs and blood. The results obtained indicate the prospects for further studies of 177Lu-EDTMP and the possibility of its clinical application for the treatment of skeletal metastases.

Determination of the half-life of 161Tb

161Tb has potential applications in targeted radionuclide therapy and nuclear forensic science. However, the half-lives of 161Tb in previous studies show a discrepancy. In this study, 161Tb samples were produced by irradiating 160Gd2O3 with thermal neutron flux. A series of procedures were applied to extract a pure 161Tb solution and three solid samples were prepared. The half-life of 161Tb has been measured with a high-purity germanium (HPGe) detector. The time-dependency of the 161Tb activity was followed by assessing the count rate of their characteristic gamma-ray emissions at 48.9 keV and 74.6 keV over a period of 33–43 days. The experiment and uncertainty budget are discussed in detail. Different uncertainty propagation equations were applied for random uncertainties, medium-frequency deviations and potential systematic errors. The result for the 161Tb half-life of 6.967 (11) d was determined by the weighted mean of half-lives from three samples, which confirms that the half-life is longer than the of the current evaluated half-life of 6.89 (2) d. From all available quoted experimental values, a recommended half-life of 6.934 (14) d was determined by the power-moderated method (PMM). Based on recent four published half-life values, a half-life of 161Tb of 6.9582 (33) d was determined by the PMM analysis.

Alpha Decay Half-Lives Calculation of Even-Even Nuclei in the62≤Z≤100Region using Woods-Saxon Potential

Alpha decay properties of even-even nuclei in the 62 ≤ Z ≤ 100 region are investigated within the Unified Fission Model based on a Modified Woods-Saxon potential. The computed alpha decay half-lives are compared to experimental data and are found to be in good agreement with it. The acquired pattern of the variation of alpha decay half-lives as a function of neutron number are explained by the nuclear shell effect. The experimental alpha decay energy Q is found to have an inverse relation with the alpha decay half-lives. This work has shown that the Unified Fission Model based on a Modified Woods-Saxon potential is sufficient to obtain the values of alpha decay half-lives.

Modelling the Impact of the COVID-19 Pandemic on Some Nigerian Sectorial Stocks: Evidence from GARCH Models with Structural Breaks

This study provides evidence of the impact of COVID-19 on five (5) Nigerian Stock Exchange (NSE) sectorial stocks (NSE Insurance, NSE Banking, NSE Oil and Gas, NSE Food and Beverages, and NSE Consumer Goods). To achieve the goal of this paper, daily stock prices were obtained from a secondary source ranging from 2 January 2020 to 25 March 2021. Because of the importance of incorporating structural breaks in modelling stock returns, the Zivot–Andrews unit root test revealed 20 January 2021, 26 March 2020, 27 July 2020, 23 March 2020 and 23 March 2020 as potential break points for NSE Insurance, NSE Food, Beverages and Tobacco, NSE Oil and Gas, NSE Banking, and NSE Consumer Goods, respectively. This study investigates the volatility in daily stock returns for the five (5) Nigerian Stock Exchange (NSE) sectorial stocks using nine versions of GARCH models (sGARCH, girGARCH, eGARCH, iGARCH, aPARCH, TGARCH, NGARCH, NAGARCH, and AVGARCH); in addition, the half-life and persistence values were obtained. The study used the Student t- and skewed Student t-distributions. The results from the GARCH models revealed a negative impact of COVID-19 on the NSE Insurance, NSE Food, Beverages and Tobacco, NSE Banking, and NSE Consumer Goods stock returns; however, the NSE Oil and Gas returns showed a positive correlation with the COVID-19 pandemic. This study recommends that the shareholders, investors, and policy players in the Nigerian Stock Exchange markets should be adequately prepared in the form of diversification of investment in stocks that can withstand future possible crises in the market.

Search for exotic physics in double-β decays with GERDA Phase II

A search for Beyond the Standard Model double-β decay modes of 76Ge has been performed with data collected during the Phase II of the GERmanium Detector Array (Gerda) experiment,located at the LaboratoriNazionali del Gran Sasso of INFN (Italy). Improved limits on the decays involving Majorons have been obtained, compared to previous experiments with 76Ge, with half-life values on the order of 1023 yr. For the first time with 76Ge, limits on Lorentz invariance violation effects in double-β decay have beenobtained. The isotropic coefficient åof (3), which embeds Lorentzviolation in double-β decay, has been constrained at the order of 10-6 GeV. We alsoset the first experimental limits on the search for light exotic fermions in double-β decay,including sterile neutrinos.

Encapsulation behavior of curcumin in heteroprotein complex coacervates and precipitates fabricated from β-conglycinin and lysozyme

The associative phase separation of oppositely charged biopolymers produces liquid-like coacervates or solid-like precipitates, whereas the effect of the physical state difference on applications is often overlooked. This study investigated the application of complexes coacervates and precipitates fabricated from β-conglycinin (β-CG) and lysozyme (LYS) for the encapsulation of curcumin. The β-CG-LYS complexes encapsulating curcumin at charge stoichiometric ratios appeared as coacervates at pH 6 and precipitates at pH 7 and 8. The curcumin encapsulation efficiency and loading capacity of these complexes reached 95% and 410–486 μg/mg. Coacervates and precipitates both significantly improved the curcumin stability when exposed to light and heat treatment. During storage, the curcumin in coacervates had an extremely long half-life value (t 1/2 ), whereas curcumin in the precipitates had a short t 1/2 . When the coacervates encapsulating curcumin adhered to the bottom of the cuvette, 35.2% of the curcumin was still retained after rinsing with ethanol 30 times. The β-CG-LYS coacervates were promising carriers to encapsulate functional molecules, which may be used as functional dressings and coatings. • Curcumin did not affect phase behavior of β-CG-LYS complex coacervation. • The encapsulation efficiency of curcumin in coacervates exceeded 95%. • The loading capacity of curcumin in coacervates exceeded 290 μg/mg. • β-CG-LYS coacervates endowed the curcumin with long-term storage stability. • β-CG-LYS coacervates have potential as functional dressings and coatings.

Synthesis and dilute aqueous solution properties of cationic antistatic surfactant functionalized with hydroxyl and ether groups

Abstract Polyester fibers tend to generate and accumulate electrical charges under friction and induction. This significantly affects the production and use process and even poses the risk of electric shocks and fire. Quaternary ammonium salt surfactants with a positive charge can be adsorbed on negatively charged polyester fibers and have excellent antistatic properties. Therefore, we have synthesised a cationic antistatic surfactant functionalised with hydroxyl and ether groups: N-hexadecyl-N,N-dimethyl-N-butanoxy glycerol ether ammonium chloride (HDBGA). The structure was characterized by 1H NMR, FTIR and ESI/MS. The excellent properties of HDBGA in aqueous solution were investigated by measuring the Krafft point (TK), surface tension, conductivity, and steady-state fluorescence. Also antistatic tests were carried out. The results show that the TK of HDBGA is below 0 °C indicating that it can still be applied in cold water. The new quaternary ammonium compound could effectively decrease the surface tension of aqueous solution to 31.28 mN m−1, where the critical micelle concentration (CMC) at 298.15 K was 3.83 × 10−4 mol L−1. In addition, the static electricity and static half-life values of the polyester cloths treated with the HDBGA solutions were also measured, as well as the effects on the fabric properties. The product exhibited excellent antistatic properties and satisfactory wash resistance, and the fabric fibers were not damaged.

In vitro and in vivo evaluation of clarithromycin solid dispersion prepared by spray-drying

The aim of this study was to develop solid dispersions (SDs) of clarithromycin (CLA) using hydrophilic polymers hydroxypropyl methylcellulose (HPMC) and xanthan gum (XNG) as drug carriers. An in vitro dissolution study was performed in dissolution media of pH 6.8, and the results were compared with those of standard drugs. In vivo pharmacokinetic studies were carried out on an animal model (rabbits). The thermal behavior of each SD formulation was studied using differential scanning calorimetry analysis. It was concluded from the results that the crystalline nature of CLA had been transformed into an amorphous form in SDs. Pharmacokinetic parameters were observed to improve in HPMC- as well as XNG-based SDs compared with those of the standard drug. Additionally, powder X-ray diffraction analysis also confirmed the phase transition (crystalline to amorphous) of the drug present in SDs. Higher values of C max were found in the case of HPMC-based SDs, whereas t max values were prolonged in SDs based on XNG. Additionally, the enhanced half-life values indicated that SDs would have the potential to achieve a once-daily dose and improved patient compliance of drugs. Hence, the formulated SDs of a poorly soluble drug, based on HPMC and XNG as carriers, exhibited a more hydrophilic nature with enhanced aqueous solubility and therefore improved bioavailability compared with that of a standard drug.

Development of an in vitro model to estimate mass transfer from the anterior cavity

Knowledge of drug mass transfer from the anterior chamber via the iris-lens barrier has important implications for the development of front of the eye medicines that can also deliver drugs to the vitreous cavity. Here, the design and evaluation of a novel in vitro model that estimates anterior clearance (CL) kinetics is described. To mimic some aspects of the human eye to aid with pharmaceutical modelling, the model incorporated a simulation of aqueous inflow from the ciliary inlet at the physiological flow rate, two CL elimination pathways [anterior hyaloid pathway and retina choroid sclera (RCS) pathway], human cavity dimensions and use of simulated vitreous fluid (SVF). An eye movement platform that incorporated 3 different eye movements (smooth pursuit, microsaccadic and saccadic) was tested against the control (no movement) to observe any difference in anterior kinetics profile and drug convection to the posterior cavity. Both timolol and brimonidine injected in the intracameral space were evaluated in the new in vitro prototype. An initial release study with one selected eye movement (smooth pursuit) with timolol (6.8 ± 0.4 µg, 30 μL) and brimonidine (15.3 ± 1.5 µg, 30 μL) showed half-life values of 105.3 and 97.8 min respectively in the anterior cavity (AC) space. Another study evaluated the effect of all eye movements against control with both drugs with higher doses of timolol (146.0 ± 39.1 μg, 25 μL) and brimonidine (134.5 ± 39.5 μg, 25 μL). The amounts of timolol in the back of the eye (RCS membrane and outflow) were 0.07 ± 0.05%, 1.36 ± 0.88%, 1.55 ± 1.03% and 0.98 ± 0.06% by 8 h with smooth pursuit, microsaccadic, saccadic and no movement respectively; whereas brimonidine amounts were 0.70 ± 0.21%, 0.94 ± 0.40%, 1.48 ± 1.02%, and 0.76 ± 0.33% respectively. A small amount of both drugs was seen in other compartments in the model (lens part, iris part, hyaloid membrane part and silicone cornea). These results indicate that this model can be used to determine transfer of small molecules via the iris-lens barrier to help optimise front of the eye formulations to treat tissues further back in the eye.

Identification and Dissipation of Chlorpyrifos and Its Main Metabolite 3,5,6-TCP during Wheat Growth with UPLC-QTOF/MS.

Ultrahigh-performance liquid chromatography system coupled to a hybrid quadrupole time-of-flight mass spectrometer (UPLC-QTOF/MS) technology was used to investigate the degradation and metabolism of chlorpyrifos during wheat growth by spraying plants with different doses of chlorpyrifos 7 days after the flowering and filling stage. We analyzed and identified chlorpyrifos metabolites in different parts of wheat in full-scan MSE mode, and established a chlorpyrifos metabolite screening library using UNIFI software. The results show that the residues of chlorpyrifos in wheat ears, leaves, and stems exhibited a decreasing trend with the prolongation of application time, and the degradation kinetics could be fitted with the first-order kinetic equation Ct = C0 e−kt. The initial residues of chlorpyrifos in different parts of the wheat were different, in the order of leaves > wheat ears > stems. The degradation rate of chlorpyrifos under field conditions is relatively fast, and the half-life value is 2.33−5.05 days. Chlorpyrifos can undergo a nucleophilic addition substitution reaction under the action of hydrolase to generate secondary metabolite 3,5,6-trichloro-2-pyridinol (3,5,6-TCP). The residual amount of 3,5,6-TCP in each part of wheat first showed an increasing trend and then decreased over time. It reached the maximum on the 3rd, 7th, or 11th day after application, and then gradually degraded. Considering that 3,5,6-TCP is a biomarker with potential threats to humans and animals, it is recommended that 3,5,6-TCP be included in the relevant regulations for dietary exposure risk assessment.

Pharmacokinetics and Pharmacodynamics of Nipocalimab Administered at Different Rates of Intravenous Infusion in Healthy Participants: Results of a Phase 1 Placebo-Controlled Single-Dose Study

Background: Warm autoimmune hemolytic anemia (wAIHA) is a rare autoimmune condition driven by autoantibodies that can significantly impact a patient's quality of life. wAIHA is characterized by the premature destruction of red blood cells (RBCs) in the presence of autoantibodies which preferentially bind to RBCs at 37°C. There is currently no approved treatment for wAIHA. Patients with severely symptomatic anemia are typically managed with corticosteroids and rituximab, both of which are associated with potential relapse and adverse events. Nipocalimab, which is in clinical development for the treatment of wAIHA (NCT04119050), is a fully human, aglycosylated, effectorless IgG1 monoclonal antibody that targets the IgG binding site on the neonatal Fc receptor (FcRn) with high affinity to lower circulating IgG levels. This study assessed the pharmacokinetics (PK) and pharmacodynamics (PD) of single doses of nipocalimab administered at different IV infusion rates in healthy adults to support the potential use of shortened infusions in future studies. Nipocalimab was generally safe and well-tolerated at all doses and infusion rates; detailed safety results have been presented separately [Leu JH, et al. EHA 2022. Presentation P1534]. Methods: The trial was a single dose, sequential, randomized, double-blind, placebo-controlled, escalating dose and infusion rate study. Eligible participants were males or females aged 18-55 years with no clinically significant medical or physical conditions. Participants were randomized to 1 of 5 cohorts (n=8 per cohort [6 nipocalimab, 2 placebo]) to receive nipocalimab 30 mg/kg IV infused over 60, 30, 15 or 7.5 min (0.5, 1, 2, or 4 mg/kg/min), nipocalimab 60 mg/kg IV infused over 15 min (4 mg/kg/min) or matching placebo. Escalation to the next dose level was permitted following review by a safety monitoring committee. Pharmacokinetic sampling of nipocalimab was conducted predose, midpoint of infusion (MOI), end of infusion (EOI), EOI + 0.083h, EOI + 0.25h, EOI + 1h, start of infusion + 24h, Day 8, and Day 15 postdose; MOI and EOI varied for each dose. In terms of PD, total serum IgG was assessed. Results: A total of 40 participants (70% female, 93% white) received study drug, of which 30 were included in the PK analysis; 39 completed the study. Mean serum nipocalimab concentration-time profiles were similar following all 30 mg/kg doses regardless of infusion rate; mean serum concentrations were ~2 times higher following a 60 mg/kg infusion. Nipocalimab remained detectable up to ~169 hours postdose for 30 mg/kg groups and ~337 hours postdose for the 60 mg/kg group. Geometric mean peak (Cmax) and overall exposure (AUC) to nipocalimab were unaffected by infusion rate when administered at 30 mg/kg. Following a 60 mg/kg infusion, AUCs were 2.4-2.8 times higher and Cmax was 2.0-2.2 times higher than with 30 mg/kg infusions. Median Tmax was approximately at EOI following the 60 mg/kg infusion. Mean half-life (t½) values were similar in all treatment groups. In terms of total serum IgG, changes from baseline were decreased among all nipocalimab cohorts at all postdose time points. The maximum decrease in mean serum IgG levels was 79% at day 15 with nipocalimab 60 mg/kg. Conclusion: Nipocalimab Cmax and AUC were not affected by infusion rates when given at a dose of 30 mg/kg, but Tmax was delayed at the fastest infusion rates. Following the 60 mg/kg infusion, peak and overall nipocalimab exposures were 2-2.8 times higher than following 30 mg/kg infusions.

Two-proton radioactivity within a Coulomb and proximity potential model for deformed nuclei

The half-lives of two-proton $(2p)$ emitters $^{6}\mathrm{Be}$, $^{12}\mathrm{O}$, $^{16}\mathrm{Ne}$, $^{19}\mathrm{Mg}$, $^{45}\mathrm{Fe}$, $^{48}\mathrm{Ni}$, $^{54}\mathrm{Zn}$, and $^{67}\mathrm{Kr}$ have been predicted using the Coulomb and proximity potential model for deformed nuclei (CPPMDN) incorporating ground-state deformation (${\ensuremath{\beta}}_{2}$) and orientation effect, and the predicted values are compared with experimental data. As predicted values are in agreement with experimental data I extended my studies to 51 nuclei, whose decay are energetically possible with released energy ${Q}_{2p}&gt;0$ for which $2p$ radioactivity is not yet experimentally detected, and the predicted half-life values are compared with other theoretical models/formulas. I hope the future experimental investigations will be guided by these predictions. The new Geiger Nuttall plot connecting ${log}_{10}[{T}_{1/2}(s)]$ computed using the CPPMDN versus $[{Z}_{d}^{0.8}+{\ensuremath{\ell}}^{\ensuremath{\beta}}]{Q}_{2p}^{\ensuremath{-}1/2}$ is found to be linear which shows the reliability of my calculations. It is found for the first time that $2p$ radioactivity also obeys the linear nature of a universal curve connecting ${log}_{10}[{T}_{1/2}(s)]$ versus $\ensuremath{-}lnP$ as that of the proton, $\ensuremath{\alpha}$, and cluster radioactivity.