Optimal Exposure Research Articles

Optimization of a Pre-Sowing Treatment of Corn Seeds with Low-Frequency Pulse Electric Field to Improve the Germination and Development of Seedlings

Corn is one of the key forage crops in agriculture. However, corn production in Russia still remains behind of its demand, so the search and development of technologies allowing to improve its yield are very relevant. Pre-sowing treatment of seeds of corn and other crops with physical fields provides stimulation of the growth and development of plants, but its efficiency depends on some parameters including duration of such treatment. The laboratory evaluation of the effect of a pre-planting treatment of corn seeds with low-frequency pulse electric field for 1–9 h on their germination, average lengths of the coleoptile and radicle root, and the number of seminal roots made it possible to determine the optimum exposure time (4 h) providing a significant improvement of germination (+26.7% of the control) and increase in the coleoptile length (+21.2% of the control). The maximum negative effect was revealed for a 5-h exposure; it resulted in a significant reduction of the coleoptile and radicle root lengths (421.7 and 16.3% of the control, respectively), as well as the reduction of the average number of seminal roots (4.8% of the control).

Research on Image Enhancement Algorithm Based on Artificial Intelligence

With the continuous development of social science and technology, people have higher and higher requirements for image quality. This paper integrates artificial intelligence technology and proposes a low-illuminance panoramic image enhancement algorithm based on simulated multi-exposure fusion. First, the image information content is used as a metric to estimate the optimal exposure rate, and the brightness mapping function is used to enhance the V component, and the low-illuminance. The image and the overexposed image are input, the medium exposure image is synthesized by the exposure interpolation method, and the low illumination image, the medium exposure image and the overexposure image are merged using a multi-scale fusion strategy to obtain the fused image, which is corrected by a multi-scale detail enhancement algorithm. After the fusion, the details are enhanced to obtain the final enhanced image. Practice has proved that the algorithm can effectively improve the image quality.

Hourly temperature variability and mortality in 31 major Chinese cities: Effect modification by individual characteristics, season and temperature zone

In the context of ongoing climate change, temperature variability (TV) has been considered as an important trigger of death. However, evidence of association between mortality and hourly temperature variability (HTV) is scarce at the multi-city level, and the time window of health effects of HTV is lack of investigation. This study aims at quantifying the mortality risk and burden of HTV and exploring subpopulations susceptible to HTV from a large-scale multi-city perspective. Data on daily number of deaths and meteorology were collected for 31 Chinese major cities during 2007-2013. HTV was calculated as the standard deviation of hourly temperature within a few days. The optimal exposure period of HTV was chosen according to multiple scientific criteria. A quasi-Poisson regression combined with distributed lag nonlinear model was used to assess the city-specific HTV-mortality associations. Then, meta-analysis was further applied to pool city-specific effect estimates. Finally, we calculated the fraction of mortality attributable to HTV. Stratification analyses were conducted by individual characteristics (i.e. age, sex, and educational attainment), season, and region. HTV calculated in a relatively long-time window like 18 d (HTV0-17) could capture the impact of HTV adequately. Per 1°C raise of HTV0-17 associated with 1.38% (95%CI: 0.77, 1.99) increase of non-accidental mortality. During the study period, 5.47% (95%CI: 1.06, 9.64) of non-accidental mortality could be attributed to HTV. The females, the elderly, and individuals with low education level were more susceptible to HTV than their counterparts, respectively. Moreover, a stronger HTV-mortality association was observed in individuals who live in warmer season and temperature zone. HTV is associated with a considerable mortality burden, which may be modified by season, geographic and individual-level factors. Our findings highlight the practical importance of establishing early warning systems and promoting health education to mitigate the impacts of temperature variability.

Photodynamic reparative skin regeneration using application of photosensitizer gel based on chlorin e6

The results of a study of the clinical effectiveness of the correction of involutional changes in the skin by the method of photodynamic therapy (PDT) with the use of a photosensitizer gel (PS), the active substance of which is the trismeglumine salt of chlorin e6, are presented. The data of fluorescence spectroscopy for monitoring the level of PS fluorescence in order to determine the optimal time of its exposure are demonstrated. The study of the optimal exposure time involved 80 patients with different skin phototypes. The study of the effectiveness of PDT involved 42 patients aged 44–68 years with signs of chrono- and photoaging. The PDT procedure was performed by irradiating the entire surface treated with the PS with a power density of 100 mW/cm2, a light dose of 120–140 J/cm2, a laser radiation wavelength of 660 nm, and a light beam area of 400–800 cm2. It was found that exposure to PS for 10–20 min gives the highest fluorescence and does not depend on the skin phototype. The clinical effect of PDT was achieved in 85.7% of patients; there were no negative subjective sensations. Moisture metrics increased on the skin of the face by 53%, reaching the control values in young healthy volunteers, on the skin of the hands - by 64%. Elastometry indicators on the skin of the face and hands increased by 19% and 16%, respectively. Thus, the PDT procedure with PS based on chlorin e6 is an effective method for correcting involutional changes in the skin, leads to a pronounced clinical effect, improves the parameters of skin moisture measurement and elastometry, and passes without undesirable local reactions. Optical coherence tomography showed an increase in collagen ordering.

Yttrium-90 Radioembolization in the VX2 Rabbit Model: Radiation Safety and Factors Influencing Delivery Efficiency

The purpose of this study was to define the optimal infusion parameters and operator radiation exposure for yttrium-90 (90Y) radioembolization in the VX2 rabbit model of liver cancer. Forty-one rabbits with VX2 were treated with glass microspheres with vial sizes of 1, 3, and 5 GBq. The mean administered activity was 51.5 MBq (95% CI, 39.1–63.9). Delivery efficiency improved with 1 GBq versus with 3 GBq (residual 11.0% vs 46.4%, respectively; P = .0013) and improved with 1 GBq versus with 5 GBq (residual 11.0% vs 33.8%, respectively; P = .0060). The mean operator extremity exposure was 41.7 μSv/infusion. The optimal minimum infusion volume and rate was 49 mL and 21 mL/min, respectively. Fecal elimination occurred with microsphere uptake in the gallbladder at 1 and 2 weeks. 90Y radioembolization can be safely and efficiently performed in the VX2 rabbit model. Methodological considerations as a “how-to” for the setup of a preclinical 90Y laboratory are included to support future translational research.

Influence of cryogenic liquid nitrogen cooling and thermal shocks on petro-physical and morphological characteristics of Eagle Ford shale

Eagle Ford shale formations have great hydrocarbon potential to minimise the supply and demand problems of the overgrowing population. Whereas, due to reduced permeability and marginal porosity, it is very difficult to produce from these formations. Previously, hydraulic fracturing and acidizing techniques are used to produce the hydrocarbons from tight gas shale formations; however, due to technical difficulties and environmental problems have led to a ban on these techniques in many countries. Therefore, it is suggested to use water-less fracturing methods to avoid these problems. Recently, liquid nitrogen (LN2) cooling have shown a great potential to mitigate technical and environmental flaws, which works on the principle of providing sudden thermal shocks in the pore matrix, thus inducing micro-cracks and enhancing the petro-physical potential.In this study, we have collected tight gas shale samples from the Eagle Ford shale's Upper Late Cretaceous geologic formation in the United States. Initially, these samples were exposed to LN2 for various time intervals of 30, 60, and 90 min and were characterised based on their petro-physical, morphology, topography, and rock mechanical properties before and after LN2 exposure. To accomplish that, various techniques were used such as core flooding, porosity determination, microstructural characterisation via field emission scanning electron spectroscopy (FESEM) and energy dispersive spectroscopy (EDS), topographic characterisation via atomic force microscopy (AFM), and rock mechanical characterisation via nano-indentation technique.It is evident from our results that LN2 cooling has a substantive effect on petro-physical properties by increasing permeability from 12 nano-Darcy (nD) to 2.6 milli-Darcy (mD) and porosity from 2.32% to 4.46%. Similarly, topographic properties have shown an increase in surface roughness from 177 nm to 692 nm, and hardness (indentation moduli, GPa) was substantially reduced due to optimum exposure of LN2 at 90 min. Further, thermal shocks of LN2 cooling have induced vivid micro-cracks in the pore matrix up to 7 μm. In a nutshell, it is vital to augment the effects of LN2 cooling on microstructural, petro-physical, topography, and rock mechanical properties for better understanding in the development of hydrocarbon potential in Eagle Ford shale formations.

Repurposing Cefazolin-Avibactam for the Treatment of Drug Resistant Mycobacterium tuberculosis.

Background: While tuberculosis (TB) is curable and preventable, the most effective first-line antibiotics cannot kill multi-drug resistant (MDR) Mycobacterium tuberculosis (Mtb). Therefore, effective drugs are needed to combat MDR-TB, especially in children. Our objective was to repurpose cefazolin for MDR-TB treatment in children using principles of pharmacokinetic/pharmacodynamics (PK/PD). Methods: Cefazolin minimum inhibitory concentration (MIC) was identified in 17 clinical Mtb strains, with and without combination of the β-lactamase inhibitor, avibactam. Next, dose-ranging studies were performed using the intracellular hollow fiber model of TB (HFS-TB) to identify the optimal cefazolin exposure. Monte Carlo experiments were then performed in 10,000 children for optimal dose identification based on cumulative fraction of response (CFR) and Mtb susceptibility breakpoint in three age-groups. Results: Avibactam reduced the cefazolin MICs by five tube dilutions. Cefazolin-avibactam demonstrated maximal kill of 4.85 log10 CFU/mL in the intracellular HFS-TB over 28 days. The % time above MIC associated with maximal effect (EC80) was 46.76% (95% confidence interval: 43.04–50.49%) of dosing interval. For 100 mg/kg once or twice daily, the CFR was 8.46 and 61.39% in children <3 years with disseminated TB, 9.70 and 84.07% for 3–5 years-old children, and 17.20 and 76.13% for 12–15 years-old children. The PK/PD-derived susceptibility breakpoint was dose dependent at 1–2 mg/L. Conclusion: Cefazolin-avibactam combination demonstrates efficacy against both drug susceptible and MDR-TB clinical strains in the HFS-TB and could potentially be used to treat children with tuberculosis. Clinical studies are warranted to validate our findings.

Optimizing Visualization in the Pelvis: When More Trendelenburg Is Not Enough

<h3>Study Objective</h3> To identify challenges to visualizing the pelvis during laparoscopy, demonstrate pre-operative steps to aid visualization, and illustrate intraoperative techniques to improve visualization. <h3>Design</h3> Video demonstration. <h3>Setting</h3> Operating room – room set-up, patient positioning, surgical techniques. <h3>Patients or Participants</h3> N/A. <h3>Interventions</h3> Video demonstration. <h3>Measurements and Main Results</h3> NA. <h3>Conclusion</h3> While several barriers to optimal access and exposure in the pelvis may exist, visualization can be improved by: having a consistent and deliberate approach to operating room setup and patient positioning; using a midline port, robust uterine manipulator, and angled laparoscope; and employing temporary retraction sutures when necessary. Maximizing visualization maximizes patient safety by preventing inadvertent injury, surgeon frustration, and prolonged operating times.

How Much Information Is Required to Time the Market?

In this article, the authors present an analytical explanation for why it can be difficult to devise a successful market timing strategy. The authors derive formulas to estimate the minimum required information coefficient for a timing strategy to outperform a buy-and-hold market benchmark, both with and without an alpha target. They show that markets with high Sharpe ratios and those that have low volatility are by nature hard to time. They also show that having high market exposure in a market timing strategy is generally beneficial; however, there can be a critical point beyond which additional market exposure makes timing more difficult. The authors extend the model to cover practical considerations such as transaction costs, skewness and fat tails, and market timing with two correlated assets. Finally, they present a case study to illustrate how investors could apply their framework to choose the optimal market exposure in a market timing strategy using the S&amp;P 500. <b>Key Findings</b> ▪ Under a bivariate normal framework, the authors show that the expected return of a timing strategy comes in two additive parts: one part driven by timing information and the other driven by average market exposure. ▪ There is generally a theoretical nonzero information threshold for a timing strategy to beat a buy-and-hold benchmark. This threshold can serve as a useful guide to determine whether a timing strategy is likely to succeed, complementing historical backtests. ▪ Although an investor can increase timing strategy return by increasing average market exposure without having more timing information, the difficulty of beating a buy-and-hold benchmark with an alpha target increases dramatically as average market exposure becomes very high.

Robust portfolio choice under the 4/2 stochastic volatility model

Abstract This paper provides the first optimal portfolio analysis for a constant relative risk-averse and ambiguity-averse investor under the state-of-the-art 4/2 stochastic volatility model in a complete market setting. We determine the robust optimal strategy and the worst case measure by allowing separate levels of uncertainty for variance and stock drivers. Technical conditions for well-defined solutions are detailed together with a verification result. The robust optimal investment exposure displays a dependence on current volatility levels similar to the non-robust case further impacted by the ambiguity-aversion level. Using real-world parameters, the numerical analysis finds that wealth-equivalent losses (WELs) from ignoring uncertainty or market completeness are moderate. On the other hand, WELs for investors who follow simpler but popular strategies, such as Heston (1/2 model) and Merton (geometric Brownian motion [GBM] model), could be quite substantial, of up to 24 and 51%, respectively. This latest analysis comes from new non-affine representations for the suboptimal value function of the 1/2 and GBM strategies.

EXPRESS METHOD FOR DETERMINATION OF GENERAL FEED TOXICITY USING BIOLUMINESCENT MICROORGANISMS PHOTOBACTERIUM PHOSPHOREUM

The aim of the work was to develop an express method for determining the general toxicity of feed using bioluminescent microorganisms Photobacterium phosphoreum. The article describes the stages of development and the algorithm for the implementation of the express method. The development of an express method for biotesting feeds using photobacteria as a biosensor was to determine the possibility of Ph. рhosphoreum to provide an adequate assessment in the event of the action of toxicants, to test the preparation of feed samples for research and to establish the optimal exposure to determine the toxicity of the feed: the optimal feed weight was 10.0 g of extractant ethanol with a volume of 20.0 cm3; the method of extraction (vigorous shaking (15-20) min or extraction with periodic stirring for 24 hours, and the exposure before the study – (20-25) min.&#x0D; The algorithm of the express method for determining the total toxicity of feed using bioluminescent microorganisms Photobacterium phosphoreum is as follows: a sample of feed weighing 10.0 g is crushed, transferred to a glass bottle, filled with 96° ethanol with a volume of 20 cm3 (this volume can be brought up to 50 cm3, so that alcohol completely covered the sample) and extracted with vigorous shaking (15-20) min. or left for 24 hours, then centrifuged at (1.5-2.0) thous. / min 10 min, after which the supernatant liquid is taken and examined on an EMILITE-1003 A luminometer. During testing, 0.02 cm3 of extract is added to the culture liquid in a volume of 1.0 cm3, the exposure time is noted and changes in the luminescence intensity are recorded on the device through (20-25) min. Under the same conditions, 96° ethanol was added as a control. Measurements are carried out sequentially or in pairs of control-experience, or at once all replicates of control samples, and then research ones. To obtain more reliable values, we recommend examining at least 4 replicates of samples (the number of replicates can be increased to 10).

Formation of holographic diffraction gratings in thin films of chalcogenide glassy semiconductors

The paper presents a study of the formation of holographic diffraction gratings in thin films of chalcogenide glassy semiconductors. The recording process of holographic gratings at the argon-laser radiation wave length 488 nm and the process of chemical etching that enables the formation of а relief holographic grating are analysed. The optimum conditions for the formation of diffraction gratings in films of arsenic sulfide As2S3 are defined. It is shown that at the 488 nm wave length of an argon laser the optimum exposure comes to ∼5–8 J/cm2. At the recording stage a quasi-phase (relief-phase) grating is formed, with the diffraction efficiency on the order of a few per cent. Etching of the exposed sample with a solution of NaOH alkali in deionised water and isopropanol makes it possible to increase considerably the relief depth and to improve the diffraction efficiency of a thin diffraction grating approximately up to 20 % for the red spectral region, and to approach the maximal value ∼34 % for the near infra-red region. The results of the study considered look promising for the creation of relief holographic gratings which are essential in present-day optical instrument building (production of spectral devices, holographic sights, and the like).

Cinnamaldehyde promotes the defense response in postharvest citrus fruit inoculated with Penicillium digitatum and Geotrichum citri-aurantii

Induced resistance in harvested fruit and vegetables is a superior strategy to reduce postharvest decay. In the present study, Cinnamaldehyde (CA) was applied to investigate for its induced resistance against Penicillium digitatum and Geotrichum citri-aurantii. The results showed that 5250 mg CA/L wax was effective concentration in inducing the resistance of citrus fruit to green mold and sour rot. Wax+ CA (WCA) reduced significantly green mold and sour rot incidences at different exposure times, with 24 h being the optimal exposure time. The host reactions under infection with different pathogens were similar. During initial exposure, treatment with 5250 mg CA/L wax enhanced significantly the activities of phenylalanine ammonia-lyase (PAL), peroxidase (POD), polyphenol oxidase (PPO), β-1, 3-glucanase (GLU) and chitinase (CHT) in the presence of direct contact with the pathogen. Simultaneously, WCA induced an increase in total phenolic, flavanone and dihydroflavonol, flavone and flavonol, and lignin contents. Thus, our results suggest that treatment using 5250 mg CA/L wax can be applied early to control diseases by provoking response reactions in citrus fruit.

Innovative techniques of left atrial exposure in minimally invasive mitral valve repair.

Various atrial retractors have been developed to achieve optimal exposure of mitral valve in minimally invasive surgery. We introduce our technique of only using retraction sutures to expose mitral valve. This method is simple, efficient, and provides good exposure of the left atrium without causing traumatic injury.

EFFICIENCY OF LAND TRANSFORMATION IN THE LAND OF SOLAR ENERGY (KREMENCHUK TOWN AS AN EXAMPLE)

The article considers the problems of modern use of urban areas, which are mostly related with the lack of reasonable scientifically and economically rational land policy. The issues of rational urban land using and land management in settlements have been studied by many domestic scientists, but to achieve the goal of rational and efficient land using, there is a need to continue research on these issues, especially at the regional and local levels. In particular, this applies to the formation of the mechanism of payment for land in conditions where the collection of taxes on labor and entrepreneurship significantly exceeds the amount of payment for land and other natural resources. The article gives an example of effective transformation of reserve lands which are not provided for permanent use and rent, located in the peripheral zone of the city, in the land of solar energy. The issue is considered from the standpoint of the value of unused urban land in their ability to generate additional income. Calculations to determine the efficiency of land transformation in the land of solar energy were made on the example of the commissioned solar power plant LLC «NOVE TEPLO", which is in the northern industrial hub of Kremenchuk, Poltava region, which covers an area of ​​150.00 hectares, and the total capacity of installed solar panels 75 MW. The total income of land transformation from reserve lands to solar energy lands for 10 years and rent income from 150 hectares of land for the specified period for reserve lands in Kremenchuk according to the values ​​of capitalized rent income standards are determined. The total income after the transformation of land was almost 300 times higher than the total income received before the transformation. Rating of ground-based SES was created by using the PV GIS web application. This tool allows you to estimate the average monthly and annual energy production from a solar electrical system connected to the grid. PV GIS calculates the optimal slope and slope exposure, which maximizes annual energy production.

Impact of prenatal exposure characterization on early risk detection: Methodologic insights for the HEALthy Brain and Child Development (HBCD) study

BackgroundA major challenge in prenatal drug exposure research concerns the balance of measurement quality with sample sizes necessary to address confounders. To inform the selection of optimal exposure measures for the HEALthy Brain and Child Development (HBCD) Study, we employed integrated analysis to determine how different methods used to characterize prenatal tobacco exposure influence the detection of exposure-related risk, as reflected in normal variations in birth weight. MethodsParticipants were N = 2323 mother-infant dyads derived from 7 independent developmental cohorts harmonized on measures of exposure, outcome (birthweight), and covariates. We compared estimates of PTE-related effects on birthweight derived from linear regression models when PTE was categorized dichotomously based on any fetal exposure (30% exposed; 69% not exposed); versus categorically, based on common patterns of maternal smoking during pregnancy (never smoked 69%; quit smoking 16%; smoked intermittently 2%; smoked persistently 13%). We secondarily explored sex differences in PTE-birthweight associations across these categorization methods. ResultsWhen PTE was categorized dichotomously, exposure was associated with a − 125-g difference in birthweight (95% C.I. -173.7 – −76.6, p < .0001). When PTE was characterized categorically based on maternal smoking patterns, however, exposure was associated with either no difference in birthweight if mothers quit smoking by the end of the first trimester (B = -30.6, 95% C.I. -88.7–27.4, p = .30); or a − 221.8 g difference in birthweight if mothers did not [95% C.I. (−161.7 to −282.0); p < .001]. Qualitative sex differences were also detected though PTE x sex interactions did not reach statistical significance. Maternal smoking cessation during pregnancy was associated with a 239.3 g increase in birthweight for male infants, and a 114.0 g increase in birthweight for females infants (p = .07). ConclusionsCategorization of PTE based on patterns of maternal smoking rather than the presence or absence of exposure alone revealed striking nuances in estimates of exposure-related risk. The described method that captures both between-individual and within-individual variability in prenatal drug exposure is optimal and recommended for future developmental investigations such as the HBCD Study.

A MISSED PULMONARY ARTERY SARCOMA REQUIRING RADICAL EXCISION AND PNEUMONECTOMY: SURGICAL TECHNIQUE

<h3>BACKGROUND</h3> A 64-year-old previously well male patient was referred with a 3-month history of progressive shortness of breath (New York Heart Association class III) and non-exertional chest pain radiating to the back. TA transthoracic echocardiogram (TTE) demonstrated mild flow acceleration across the pulmonary valve, without insufficiency and estimated pulmonary pressures of 55 - 60 mmHg. Repeat CT scan identified an approximately 6 cm mass completely filling the right pulmonary artery (RPA) to the hilum and extending down the main pulmonary artery (MPA), potentially involving the pulmonary valve. The left pulmonary artery (LPA) appeared mostly spared. Multidisciplinary oncological team evaluation suggested concerns for pulmonary artery sarcoma prompting consideration for urgent radical excision with homograft reconstruction and right pneumonectomy. <h3>METHODS AND RESULTS</h3> Upon discovery of bilateral PAS in our patient, we decided intraoperatively to continue with a complete radical resection and pneumonectomy, keeping with the goal of complete curative excision. This required extensive planning for surgery including ensuring homograft availability for reconstruction of the pulmonary root and its branches. Cardioplegic arrest was utilized to allow aortic transection to provide optimal exposure posterior to the aorta to determine tumor extension. Given only partial extension into the LPA, we prioritized good margins distally towards the left lung, and used an additional pulmonary allograft for reconstruction. Complete obstruction of the RPA and tumor extension into the right lung necessitated a right pneumonectomy. Pathology confirmed intimal sarcoma with negative margins, and confirmed tumor spread into the right lung parenchyma. At 6 months follow-up, this patient is doing well with no signs of tumour recurrence. Repeat CT demonstrates a patent and functional reconstructed MPA and LPA. <h3>CONCLUSION</h3> Though this technique requires meticulous planning and surgical expertise, it offers a reasonable alternative to conventional management with greater survival benefit. The hope is this approach can build on past literature and lead to longer survival post-operation in patients diagnosed with this rare but deadly disease.

Optimisation of the AP abdomen projection for larger patient body thicknesses

IntroductionThis study aims to identify optimal exposure parameters, delivering the lowest radiation dose while maintaining images of diagnostic quality for the antero-posterior (AP) abdomen x-ray projection in large patients with an AP abdominal diameter of >22.3 cm. MethodologyThe study was composed of two phases. In phase 1, an anthropomorphic phantom (20 cm AP abdominal diameter) was repetitively radiographed while adding 3 layers (5 cm thick each) of fat onto the phantom reaching a maximum AP abdominal diameter of 35 cm. For every 5 cm thickness, images were taken at 10 kVp (kilovoltage peak) intervals, starting from 80 kVp as the standard protocol currently in use at the local medical imaging department, to 120 kVp in combination with the use of automatic exposure control (AEC). The dose area product (DAP), milliampere-second (mAs) delivered by the AEC, and measurements to calculate the signal to noise ratio (SNR) and contrast to noise ratio (CNR) were recorded. Phase 2 included image quality evaluation of the resultant images by radiographers and radiologists through absolute visual grading analysis (VGA). The resultant VGA scores were analysed using visual grading characteristics (VGC) curves. ResultsThe optimal kVp setting for AP abdominal diameters at: 20 cm, 25 cm and 30 cm was found to be 110 kVp increased from 80 kVp as the standard protocol (with a 56.5% decrease in DAP and 76.2% in mAs, a 54.2% decrease in DAP and 76.2% decrease in mAs and a 29.2% decrease in DAP and 59.7% decrease in mAs, respectively). The optimal kVp setting for AP abdominal diameter at 35 cm was found to be 120 kVp increased from 80 kvp as the standard protocol (with a 50.7% decrease in DAP and 73.4% decrease in mAs). All this was achieved while maintaining images of diagnostic quality. ConclusionTailoring the exposure parameters for large patients in radiography of the abdomen results in a significant reductions in DAP which correlates to lower patient doses while still maintaining diagnostic image quality. Implications for clinical practiceThis research study and resultant parameters may help guide clinical departments to optimise AP abdomen radiographic exposures for large patients in the clinical setting.

Exposure-toxicity relationship of cabozantinib in patients with renal cell cancer and salivary gland cancer.

Cabozantinib is registered in fixed 60 mg dose. However, 46% to 62% of patients in the registration studies needed a dose reduction due to toxicity. Improved clinical efficacy has been observed in renal cell carcinoma patients (RCC) with a cabozantinib exposure greater than 750 μg/L. In our study we explored the cabozantinib exposure in patients with different tumour types. We included RCC patients from routine care and salivary gland carcinoma (SGC) patients from a phase II study with ≥1 measured C min at steady‐state. The geometric mean (GM) C min at the starting dose, at 40 mg and at best tolerated dose (BTD) were compared between both tumour types. Forty‐seven patients were included. All SGC patients (n = 22) started with 60 mg, while 52% of RCC patients started with 40 mg. GM C min at the start dose was 1456 μg/L (95% CI: 1185‐1789) vs 682 μg/L (95% CI: 572‐812) (P < .001) for SGC and RCC patients, respectively. When dose‐normalised to 40 mg, SGC patients had a significantly higher cabozantinib exposure compared to RCC patients (C min 971 μg/L [95% CI: 790‐1193] vs 669 μg/L [95% CI: 568‐788]) (P = .005). Dose reductions due to toxicity were needed in 91% and 60% of SGC and RCC patients, respectively. Median BTD was between 20 to 30 mg for SGC and 40 mg for RCC patients. GM C min at BTD were comparable between the SGC and the RCC group, 694 μg/L (95% CI: 584‐824) vs 583 μg/L (95% CI: 496‐671) (P = .1). The observed cabozantinib exposure at BTD of approximately 600 μg/L is below the previously proposed target. Surprisingly, a comparable exposure at BTD was reached at different dosages of cabozantinib for SGC patients compared to RCC patients Further research is warranted to identify the optimal exposure and starting dose to balance efficacy and toxicity.

Development of weight and age-based dosing of daily primaquine for radical cure of vivax malaria

BackgroundIn many endemic areas, Plasmodium vivax malaria is predominantly a disease of young adults and children. International recommendations for radical cure recommend fixed target doses of 0.25 or 0.5 mg/kg/day of primaquine for 14 days in glucose-6-phosphate dehydrogenase normal patients of all ages. However, for many anti-malarial drugs, including primaquine, there is evidence that children have lower exposures than adults for the same weight-adjusted dose. The aim of the study was to develop 14-day weight-based and age-based primaquine regimens against high-frequency relapsing tropical P. vivax.MethodsThe recommended adult target dose of 0.5 mg/kg/day (30 mg in a 60 kg patient) is highly efficacious against tropical P. vivax and was assumed to produce optimal drug exposure. Primaquine doses were calculated using allometric scaling to derive a weight-based primaquine regimen over a weight range from 5 to 100 kg. Growth curves were constructed from an anthropometric database of 53,467 individuals from the Greater Mekong Subregion (GMS) to define weight-for-age relationships. The median age associated with each weight was used to derive an age-based dosing regimen from the weight-based regimen.ResultsThe proposed weight-based regimen has 5 dosing bands: (i) 5–7 kg, 5 mg, resulting in 0.71–1.0 mg/kg/day; (ii) 8–16 kg, 7.5 mg, 0.47–0.94 mg/kg/day; (iii) 17–40 kg, 15 mg, 0.38–0.88 mg/kg/day; (iv) 41–80 kg, 30 mg, 0.37–0.73 mg/kg/day; and (v) 81–100 kg, 45 mg, 0.45–0.56 mg/kg/day. The corresponding age-based regimen had 4 dosing bands: 6–11 months, 5 mg, 0.43–1.0 mg/kg/day; (ii) 1–5 years, 7.5 mg, 0.35–1.25 mg/kg/day; (iii) 6–14 years, 15 mg, 0.30–1.36 mg/kg/day; and (iv) ≥ 15 years, 30 mg, 0.35–1.07 mg/kg/day.ConclusionThe proposed weight-based regimen showed less variability around the primaquine dose within each dosing band compared to the age-based regimen and is preferred. Increased dose accuracy could be achieved by additional dosing bands for both regimens. The age-based regimen might not be applicable to regions outside the GMS, which must be based on local anthropometric data. Pharmacokinetic data in small children are needed urgently to inform the proposed regimens.