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Background Some previous works have focused on dose‐response relationship between cocoa consumption and blood pressure in Caucasians. As black subjects have lower nitric oxide bioavailability, the aim of this work was to determine the dose‐effect relation between cocoa and blood pressure in black Africans. Method One hundred and thirty healthy black African males aged 18–30 were randomly assigned into four groups: three groups consuming 10 g, 5 g, or 2 g of cocoa powder daily for three weeks and one control group that did not consume cocoa. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were measured on day 1 (D1, before any subject consumed cocoa), D8, D15, and D22. Means of the parameters at each of the four visits and changes of the means were compared among the groups. Results Significant decrease in SBP was noted in consumers of 10 g compared to controls in the 1st week, and compared to consumers of 2 g in the 2nd and 3rd weeks of follow‐up. Means and changes of DBP were statistically similar among the four groups. Conclusion Among our cohort, decrease in SBP was significantly greater in the heavy cocoa consumer group (10 g) compared to the low consumer group (2 g), but there was no statistically significant difference when compared with the intermediate consumer group (5 g). The dose‐response relationship between cocoa consumption and changes in SBP was not linear. No relationship was found between cocoa consumption and DBP., Some previous works have focused on the dose‐response relationship between cocoa consumption and blood pressure and found that the highest doses of cocoa induced the greatest drops in blood pressure. Studies have been carried out in Caucasians in whom the bioavailability of nitric oxide, which explains the effect of cocoa on blood pressure, is better than in black subjects. Carried out over three weeks among healthy black Africans, our study found significant reduction of SBP in consumers of largest amount of cocoa with no linear relationship between cocoa doses and SBP variations.

Introduction The coronavirus disease 2019 (COVID-19) pandemic has led to worldwide vaccination development efforts. In December 2020 the Pfizer BNT162b2 vaccine was approved in the United States. This study describes the first BNT162b2 vaccine dose effect on a large cohort. Methods This retrospective study examined first vaccine dose effect on serology and investigated the associations between seroconversion and age or sex. Results Serological blood tests were performed on 1898 participants following first vaccine dose; 81% were tested on day 21, before receiving the second dose (mean age 47.5 ± 12.45; median 47.7, range 18–90). Positive serology was found in 92.7% of day 21 tests. Overall positivity was 86.8%, with rates increasing from 2.5% within 1–14 days to 89.8% (14–20 days), 92.7% (21 days), and 95.9% (>21 days). Mean antibody levels 21 days after first dose were 64.3 ± 33.01 AU/ml, (range 15–373 AU/ml, median 61 AU/ml). Seropositivity was greater in females than males (88.3%. vs 83.3% respectively, p 60 years was associated with decreased likelihood of seropositivity (p

When a dose-response relationship is monotonic, the EMAX model has been shown to provide a good empirical fit for designing and analyzing dose-response data across a wide range of pharmaceutical studies. However, the EMAX model has never been applied to a finite mixture distribution. Motivated by a proposal investigating DHA dose effect on preterm birth (PTB, 41 weeks gestation) using the same model. We compared our proposed EMAX mixture model with an EMAX logistic model and an independent doses logistic model for a dichotomized endpoint using extensive simulations. Across the scenarios under consideration, the EMAX mixture model achieved higher power than the EMAX logistic model and the independent doses logistic model in detecting the effect of DHA supplementation on the PTB rate. The EMAX mixture model also resulted in smaller mean squared errors (MSE) in PTB rate estimates.

Long-term and graded dose of astaxanthin supplementation in laying hen's diet was assessed for egg fortification. Five groups of laying hens with 8 replications each were fed for 24 wk with diet supplemented astaxanthin at 0 mg/kg (control), 7.1 mg/kg, 14.2 mg/kg, 21.3 mg/kg, and 42.6 mg/kg (Basal, A7, A14, A21, and A42, respectively). The performance of laying hens, egg quality, astaxanthin concentration as well as conversion efficiency and geometric isomers proportion in yolks were assessed on wk 8 and 24. One-way analysis of variance (ANOVA) and linear and quadratic regression analyses were used to evaluate the dose effect. In parallel, the Student's t test compared the values between wk 8 and wk 24 of test within a group. Overall, the results revealed that neither production performance nor egg physical quality was affected by astaxanthin dose level and feeding duration. Following the supplementation dose, the redness of yolks (a*) increased (P < 0.001). But, the a* score in A42 (23.48) was just 3-folds the a* score in A7 (8.89). Concentration of astaxanthin in eggs was dose-level dependent showing a linear relationship (P < 0.001) with a slight declination observed in all groups on wk 24 compared to wk 8. The deposition rate of astaxanthin into egg yolk was higher in A21 and A42. The proportion of geometric isomers in egg yolk were not affected by the feeding duration. As the supplementation dose increased, all-trans isomer proportion gradually decreased in the egg yolk, while 13-cis isomer proportion rose. It was concluded that astaxanthin is an efficient carotenoid for egg fortification, which can be supplemented in diet up to 42.6 mg/kg for 24 wk without compromising the performance of laying hens or physical quality of eggs. This appreciably affects the egg yolk color and confers a better accumulation of total astaxanthin and cis isomers into eggs as the supplementation dose increases.

Background The hippocampus is a critical organ for irradiation. Thus, we explored changes in hippocampal volume according to the dose delivered and the location relative to the glioblastoma. Methods All patients were treated for glioblastoma with surgery, concomitant radiotherapy and temozolomide, and adjuvant temozolomide. Hippocampi were retrospectively delineated on three MRIs, performed at baseline, at the time of relapse, and on the last MRI available at the end of follow-up. A total of 98, 96, and 82 hippocampi were measured in the 49 patients included in the study, respectively. The patients were stratified into three subgroups according to the dose delivered to 40% of the hippocampus. In the group 1 (n = 6), the hippocampal D40% was contra D40% was 40% for both hippocampi was > 7.4 Gy. Results Regardless of the time of measurement, homolateral hippocampal volumes were significantly lower than those contralateral to the tumor. Regardless of the side, the volumes at the last MRI were significantly lower than those measured at baseline. There was a significant correlation among the decrease in hippocampal volume regardless of its side, and Dmax (p = 0.001), D98% (p = 0.028) and D40% (p = 0.0002). After adjustment for the time of MRI, these correlations remained significant. According to the D40% and volume at MRIlast, the hippocampi decreased by 4 mm3/Gy overall. Conclusions There was a significant relationship between the radiotherapy dose and decrease in hippocampal volume. However, at the lowest doses, the hippocampi seem to exhibit an adaptive increase in their volume, which could indicate a plasticity effect. Consequently, shielding at least one hippocampus by delivering the lowest possible dose is recommended so that cognitive function can be preserved. Trial registration Retrospectively registered.

Sulphurous acid derived from sulfur dioxide (SO2) emission leads to the pollution of irrigation water and the inhibition of plant growth. The safe concentration threshold of NaHSO3 in plants should be clarified to promote agricultural production. In this study, Orychophragmus violaceus seedlings were used as experimental materials and five NaHSO3 concentrations (i.e., 0, 1, 2, 5, 10 mmol·L−1) were simultaneously sprayed on the leaf surface of different seedlings separately. Leaf physiology responses under different concentrations were analyzed. The NaHSO3 did not promote photosynthesis in O. violaceus under the 1 and 2 mmol·L−1 treatments. It was conducive to the net photosynthetic rate (PN), photorespiration rate (Rp), chlorophyll content, actual photochemical quantum yield (YII) and photochemical quenching (qP) under the 5 mmol·L−1 treatment. However, quantum yield of regulated energy dissipation (YNPQ) and nonphotochemical quenching (NPQ) were inhibited. Under the 10 mmol·L−1 treatment, PN, chlorophyll content, YII, qP, dark respiration rate (Rd) and electron transport rate (ETR) showed significant decreases, while the photorespiration portion (Sp) significantly increased. Our results demonstrated that NaHSO3 provided a sulfur source for plant growth and interfered with the redox reaction of the plant itself, and its role as a photorespiratory inhibitor might be masked.

Fully oxidized β-carotene (OxBC) containing β-carotene-oxygen copolymers is proposed as an alternative to antimicrobial growth promoters. Two trials were conducted to determine the efficacy of OxBC in enhancing growth and feed intake (FI) in male and female Ross × Ross 308 broilers in Ontario, Canada, and in Ross 308 male broilers in the United Kingdom. In the first trial, 0, 1, 2, or 5 ppm OxBC were added to diets in a 20% cornstarch premix, whereas in the second trial, 0, 2, or 5 ppm OxBC were added in a 1% cornstarch or 1% corncob grits premix. In trial 1, 2, and 5 ppm OxBC improved bird final body weights (BW) compared with the unsupplemented, nonmedicated (no bacitracin methylene disalicylate included), negative control birds after 39 d of feeding under commercial conditions (P < 0.05). All levels of OxBC improved feed conversion (FCR) during the finisher period (P < 0.05), whereas 2 and 5 ppm OxBC enhanced FCR relative to the negative control group during the full production cycle (P 0.05). There were no differences among the 3 OxBC groups (P > 0.05). When birds were fed 2 ppm OxBC on corncob grits, the overall ADG, BW, and FI were lower than the respective control values (P < 0.001). Overall bird mortality was higher than expected for all groups, including the control group, but no dose effect was evident. Cornstarch was the preferred carrier for OxBC, and 2 ppm OxBC was the optimal dose under the conditions used.

This paper is devoted to analyzing the effect of gamma radiation on the behavior of optocouplers. According to a series of experiments that involve masking various parts of a chip from X-ray irradiation, the most sensitive region of the chip is determined and the design of the optocoupler is improved. Upon modification, the radiation hardness of the device more than triples.

To examine the impact of an employer-sponsored behavioral health program on depression and anxiety by assessing dose effect of psychotherapy.A retrospective data analysis of patients with baseline scores more than or equal to 10 on the Patient Health Questionnaire (PHQ9) or the Generalized Anxiety Disorder 7-item scale (GAD7). Survival analyses were conducted to assess whether those with a higher number of therapy sessions per episode (dose) achieved faster response (score reduction by 50% or below 10).Patients with medium (8 to 12 visits) or high (more than 12 visits) dose achieved faster response than those with low dose (less than eight visits; hazard ratios more than 1.5, P 0.05). No significant difference was found between the medium and high dose.Higher dose of psychotherapy is correlated with improved behavioral health outcomes, although there appears to be no incremental benefit beyond a certain level.

To explore the relationship between skin surface hydration and Trans-Epidermal Water Loss (TEWL) when simultaneously measured.Six circular skin areas of the forearms (3 per forearm, 3 cm in diameter) of 12 Caucasian women were used as models. 4 prototypes of formulae of different compositions containing glycerol at different concentrations 7%, 10% and 40% were used as models of hydrating products. One formula (glycerol-free) was used as control vehicle. Standardized applications of formulae (2 mg/cmThe new instrumental device allowed to clearly differentiate the 5 formulae (i.e. 7% vs. 10%) with regard the dose effect brought by glycerol (7%, 10%, 40%) and to record their lingering effects at T1 and T5. Both parameters were found significantly and negatively correlated, i.e. the higher the skin hydration, the lower the TEWL. The 40% concentration of glycerol, that leads to the highest skin hydration, brings a drop in the TEWL by about a two-fold factor. Skin hydration of bare skin and control/vehicle sites showed minor and non-significant changes along 5 h. Instead, the control/ vehicle slowed down the TEWL to a slight extent.The use of this new instrumental device shed a new light on the mutual and inverse relationships between skin hydration and TEWL. Results suggest that, at high concentration, glycerol leads to largely increase the water content of both epidermal and dermal compartments, possibly leading to structural changes in the skin relief.D’explorer les relations mutuelles entre l’hydratation cutanée et la perte insensible en eau (PIE) quand elles sont mesurées simultanément. MÉTHODES: 6 zones circulaires des avant-bras (3 par zone, diamètre 3 cm) de 12 femmes Caucasiennes ont été utilisées comme modèles. 4 prototypes de formules, de compositions différentes contenant du glycérol à différentes concentrations (7%, 10%, 40%) furent réalisés et utilisés comme modèles de produits hydratants. Une formule sans glycérol fut utilisée en tant que contrôle. Des applications standardisées (2 mg/cmL’utilisation de ce nouvel instrument semble apporter un éclairage nouveau sur les relations mutuelles (et inverses) entre l’hydratation cutanée et la PIE. Les résultats suggèrent qu’à forte concentration, le glycérol conduit à un fort accroissement de la teneur en eau de l’épiderme et du derme, avec de possibles conséquences structurelles du relief cutané.

Bioavailability and ecotoxicity of metals and their relation to geochemical conditions in aquatic environments were considered. It was shown that free ions are the most penetrative species of most metals, except for organometallic complexes of some metals, for example, mercury. We analyzed models for the assessment of the hazard of metal contamination of water environments using the results of thermodynamic calculations of free ion concentrations, the ability of biological receptors to bind them, and the toxic properties of the metals. A concept was developed on the main mechanisms of metal penetration and excretion and cytotoxicity of nonessential elements. A new method was proposed for the estimation of critical levels of polymetallic contamination of water on the basis of measurements of water complexation capacity and determination of the dose–effect relations between the integrated characteristics of the polymetallic contamination and indicators of the health of the ecosystems (in situ) from the results of investigations in the northern Kola Peninsula.

While doses of deferiprone up to 75 mg/kg/d have been demonstrated to be effective in cardiac iron removal, their efficacy in the reduction of liver iron has been equivocal. The aim of this study was to evaluate the effect of deferiprone dose on liver iron concentrations in adult iron overload patients.A single-centered, retrospective, cohort observational study was conducted involving 71 patients exposed to deferiprone doses up to 113 mg/kg/d between January 2009 and June 2015 for a median of 33 months.At the end of the study period, liver iron measured by R2 MRI was reduced by a mean 1.7 mg/g dw. A dose effect was observed, with incremental reductions of 2.8 mg/g dw in end of study LIC for every 10 mg/kg/d higher dose of deferiprone (P 0.001). A dose effect was also observed in end of study ferritin and cardiac iron concentration measured by T2* MRI (P 0.0001 and P = 0.048, respectively). No associations between adverse effects and deferiprone dose were observed, but there was a trend toward higher rates of agranulocytosis at higher doses and two of three hereditary hemochromatosis patients developed this complication.The present study failed to demonstrate that the use of deferiprone at90 mg/kg/d was associated with increased risk of agranulocytosis or neutropenia, but did demonstrate more effective liver iron control in iron overload patients.

Dose Effect of NPK fertilizer and Pewiwilan To Growth And Production Plant eggplant (S. melongena L.). The purpose of this study was to determine the effect of administered dose of NPK fertilizer and Pewiwilan on the growth and yield of eggplant (S. melongena L.). This research was conducted in L2 Block C Karang Single District of Tenggarong Seberang Kutai regency, which was conducted over four months from seedling to harvest, ie from April to August 2015dengan using a randomized block design (RAK) with factorial 4 X 2 each treatment was repeated four times, the first factor is dosage NPK fertilizer (P), which consists of 4 levels, namely: p0 (control), p1 (15 grams / plant), p2 (20 grams / plant), p3 ( 25 grams / plant). The second factor is Pewiwilan (W) consisting of two levels ie: w0 (without cut), w1 (with cut). Results from the study showed that the treatment dose of NPK fertilizer (P) did not significantly affect plant height age of 20 days after planting and the number of branches of productive age of 50 and 70 days after planting. But very significant effect on plant height, aged 30, 50, and 70 days after planting and the age of the plant when the first harvest, planting fruit number and weight of the fresh fruit crop. Average yields are best demonstrated by the treatment p3 (25 grams / plant). While treatment Pewiwilan (W) showed no significant effect on plant height was 20, 30, 50, and 70 days after planting, the number of branches of productive ages of 50 and 70 days after planting, as well as the age of the plant when harvested the first time, the number of fruit crops and weight fresh fruit planting. Interaction doses of NPK Pelangi and Pewiwilan not significantly affect plant height was 20, 30, 50, and 70 days after planting, the number of branches of productive ages of 50 and 70 days after planting, as well as the age of the plant when harvested the first time, the number of fruit crops and fresh fruit heavy cropping

In the deliberations over many years on the question of thresholds for the carcinogenicity of chemicals, the dominant paradigm has been the linear no-threshold (LNT) model, derived from concepts formulated in radiation mutagenicity. Based on the analogy with radiation, the key mechanistic assumption underlying the assessment of the dose-effect of chemical-induced carcinogenicity has been that any dose, no matter how low, can lead to induction of mutations, which will result in some risk of neoplasia. The LNT assumption, however, was never well founded and, its application to chemical carcinogens, does not allow for differences in their disposition or mechanisms of action. These mechanisms include DNA-reactivity and epigenetic effects, resulting from very different properties of carcinogens, leading to different dose effects. This review of the research on dose effects of chemical carcinogens administered by repeat dosing for long duration reveals that only some experiments involving what are now recognized as DNA-reactive carcinogens yielded dose effects for induction of tumors which were consistent with the absence of a threshold (for 6/14 chemicals). None of these studies, however, included low doses documented not to produce genetic or other cellular toxicities that underlie carcinogenicity. Otherwise, most dose-effect experiments, including all with epigenetic agents (7), revealed no-observed-effect-levels for tumors, indicative of subthreshold doses. Based on highly informative experimental data, including relevant mechanistic data, it is concluded that no-effect-levels exist for both carcinogen-induced precursor effects and neoplasia. Accordingly, we conclude that, at non-toxic dosages, thresholds exist for the induction of experimental cancer by all types of carcinogens.

OBJECTIVES Tramadol can cause life-threatening toxicity in overdose; however, data on its toxicity in children are lacking. This study investigates toxicity associated with tramadol ingestions in children. The hypothesis is that children will experience dose-related central nervous system and respiratory depression and seizures. METHODS A retrospective evaluation of cases from the National Poison Center Data System between January 1, 2000, and December 31, 2013, was performed. Inclusion criteria were age below 6 years and single-substance acute tramadol ingestion. For dose-effect analysis, cases with sufficient dose quantity information were included. RESULTS There were 7334 cases that met inclusion criteria. Outcomes were 84.8% no effect, 12.6% minor, 2.2% moderate, and 0.4% major effect. There was 1 fatality. Most of the children (36.4%) were treated/released from the emergency department; other management sites were home (36.4%), admission (5.9%), and others (3.2%). In the 1115 children with symptoms, drowsiness (N = 611) and vomiting (N = 178) occurred most frequently. More serious clinical effects included respiratory depression in 36 and seizures in 24 children. Of 2772 children with milligram dose recorded, there were 10 cases of respiratory depression and 6 of seizure. Median doses for respiratory depression and seizure were 225 (range, 50-600 mg) and 525 mg (range, 50-1050 mg), respectively. The minimum weight-based dose for respiratory depression/arrest was 7.9 mg/kg and for seizures, 4.8 mg/kg. CONCLUSIONS Seizure and respiratory depression are uncommon in pediatric tramadol ingestions. Given the small number of patients with dose data and lack of laboratory confirmation of dose, more studies are needed to determine the minimum dose at which medical management is recommended.

Background Birds have various plumage color patterns, and spot is a common phenotype. Herein, we conducted genome-wide association studies (GWAS) in a population of 225 ducks with different sized black spots to reveal the genetic basis of this phenomenon. Results First, we quantified the black spot phenotype within the duck population. The results showed that the uncolored area of the body surface first appeared on the ventral side. With increasing duck age, the area of the black spots was highly conserved across the whole body surface. The GWAS results identified a 198 kb (Chr4: 10,149,651 bp to 10,348,068 bp) genetic region that was significantly associated with the black spot phenotype. The conditional GWAS and linkage disequilibrium (LD) analysis further narrowed the ultimate candidate region to 167 kb (Chr4: 10,180,939 bp to 10,348,068 bp). A key gene regulating melanoblast migration and differentiation, EDNRB2 (Endothelin B receptor-like), was found in the candidate region and having significant mRNA expression level changes in embryonic duck skin tissue with different spot sizes. The significant SNPs (single nucleotide polymorphisms) associated with the EDNRB2 gene were annotated, and two mutations (Chr4: 10,180,939 T > C and Chr4: 10,190,671 A > T) were found to result in the loss of binding sites for two trans-factors, XBP1 and cMYB. The phenotypic effect of these two mutations suggested that they can regulate the size of black spots in a dose-dependent manner, and Chr4: 10,180,939 T > C was the major allele locus. Conclusions Our results revealed that EDNRB2 was the gene responsible for the variation in duck body surface spot size. Chr4: 10,180,939 T > C was the major allele that explained 49.5 % (dorsal side) and 32.9 % (ventral side) of the variation in duck body surface spot size, while 32.1 % (dorsal side) and 19.1 % (ventral side) of the variation could be explained by Chr4: 10,190,671 A > T. The trans-factor prediction also suggested that XBP1 and cMYB have the potential to interact with EDNRB2, providing new insights into the mechanism of action of these genes.

Background Chronic fatigue syndrome (CFS) is a disease with high incidence rate and great impact on life, but it lacks for specific pharmacological treatment and diagnostic indicators. In the theory of traditional Chinese medicine (TCM), fatigue is the result of Yang deficiency. Long-snake-like moxibustion, as one of a special moxa therapy, has been applied in Yang deficiency patients for thousands of years in China and it is used widely to relieve fatigue symptoms for its strong function of Yang warming. However, the does-effect relationship is unclear in the moxibustion research. Hence, we design this trial to assess the duration-effect of long-snake-like moxibustion through combining measurements of the subjective patient-reported scales with objective medical infrared imaging technology─Thermal Texture Maps (TTM). Methods This is a single-center, randomized controlled trial. Thirty healthy women and sixty female CFS patients will be recruited to receive the first TTM scanning, then CFS patients will be allocated to 60-minute long-snake-like moxibustion (Group A) and 30-minute long-snake-like moxibustion (Group B) equally. These two groups will receive corresponding treatment once a day, three sessions per week every other day for consecutive 4 weeks. The second TTM scanning will be employed for CFS patients after the end of treatment. The primary outcome will be the score improvement of the Fatigue scale-14 (FS-14). Secondary outcomes include the change of the Self-rating depression scale (SDS),the Self-rating anxiety scale (SAS), and the Symptoms Scale of spleen-kidney Yang deficiency. Discussion The trial will provide evidence for the choice of treatment duration for long-snake-like moxibustion in treating CFS. The results will contribute to explore the dose-effect relationship of moxibustion, and optimize the efficacy of moxibustion therapy. Trial registration: Chinese Clinical Trail Registry (No. ChiCTR2000041000), on 16th December, 2020, http://www.chictr.org.cn/showproj.aspx?proj=62488

Purpose/Objective(s) The effects of cancer treatment exposures on the brain are poorly understood, particularly for cancers outside of the central nervous system. Patients with head and neck cancer (HNC) treated with radiation (RT) often have portions of their brain exposed to moderate doses of radiation, particularly within the posterior fossa. The purpose of this study was to characterize changes in brain metabolism using 18-fluorodeoxyglucose (FDG) PET after HNC treatment, with emphasis on accounting for the distribution of the radiation exposure. Materials/Methods This study included patients who received RT for newly diagnosed HNC at an academic center since 2012 for whom an FDG PET scan was utilized for RT treatment planning, a subsequent PET was obtained within 6 months of completing RT, and both PET scans included the entire brain. Brain regions of interest (ROIs) were defined using the original RT treatment plans and included the intersection of the brain with the 10 Gy, 20 Gy, 30 Gy isodose lines, typically contained within the posterior fossa. The portion of the brain outside of the 3 Gy isodose line was also defined as an ROI relatively spared from radiation ( Results A total of 50 patients met the inclusion criteria. Pre-RT average SUVMean was statistically higher for the Conclusion In this population of patients receiving RT for HNC we observed a decrease in SUVMean when comparing pre- and post-RT FDG PET. The decline in SUVMean was greatest in the portion of the brain that was relatively spared from radiation. Further research is needed to clarify whether the observed changes are a direct result of radiation exposure or differences in regional brain metabolism, assess for a dose effect, and to relate changes on PET with patient-centered outcomes.

Purpose: The aim of this study was to explore the efficacy and dose effect of intradiscal injection of simvastatin sustained release hydrogel in the treatment of discogenic low back pain in rabbits.Methods: 36 female rabbits were randomly divided into G1 and G2 groups. In group G1, L1/2 was disc degeneration (group DDD), L2/3 was normal group (control group), L3/4 was medium dose treatment group (1mg/ml, DDD+ medium group), L4/5 was normal group, L5/6 was intervertebral disc degeneration + hydrogel segment (medium group). In group G2, L1 / 2 was degenerative segment, L2 / 3 was normal group, L3 / 4 was low-dose treatment segment (0.3mg/ml, DDD + low-dose group), L4 / 5 was normal group, L5 / 6 was high-dose treatment segment (3mg / ml, DDD + high-dose group). The intervertebral disc was evaluated by X-ray, MRI, water content, and hematoxylin-eosin.Result: At 12 and 24 weeks after treatment, the% DHI of control group and DDD + high were higher than those of DDD group and DDD + gel group (P

BACKGROUND Primary lower-extremity hyperhidrosis (PLEH) can be treated by CT-guided lumbar sympathetic nerve modulation using absolute ethanol. However, doses of ethanol that are too high can cause nerve injury, and doses that are too low have suboptimal results. The present study aimed to investigate the dose-effect relationship of CT-guided lumbar sympathetic nerve modulation with absolute ethanol for PLEH. MATERIAL AND METHODS The study was conducted at the First Affiliated Hospital of Jiaxing University between 07/2014 and 02/2017. Twenty participants were enrolled in each group. The doses of absolute ethanol were 2.0 ml in the R₁ group, 2.5 ml in the R₂ group, 3.0 ml in the R₃ group, 3.5 ml in the R₄ group, and 4.0 ml in the R₅ group. Treatment effectiveness was assessed according to the time to complete hyperhidrosis relief:10 min, effective; ≥10 min, non-effective. RESULTS The patient characteristics among the 5 groups were not statistically different (P0.05). The onset time and time to complete hyperhidrosis relief decreased significantly with increasing dose of absolute ethanol (P0.05). The effective rates in the 5 groups were 15.0%, 35.0%, 60.0%, 90.0%, and 100.0%, respectively. The ED₅₀ and ED₉₅ were 2.306 ml (95% CI: 2.003-2.512 ml) and 3.343 ml (95% CI: 3.051-3.962 ml), respectively. CONCLUSIONS This was the first dose-effect pilot study of consecutive PLEH patients treated by CT-guided lumbar sympathetic nerve modulation. CT-guided lumbar sympathetic nerve modulation with 2.306 ml (ED₅₀) and 3.343 ml (ED₉₅) of absolute ethanol showed treatment efficacy for PLEH. No complications were seen.

International audience; In the lifetime extension of nuclear power plants (NPPs) context, aging of electric cables has to be very well understood in order to predict their end-of-life and thus to replace them on time. Therefore, evaluation and understanding of the ageing mechanism of the cable insulating material is mandatory under conditions as close as possible of those encountered in NPPs. In this context, different formulated crosslinked polyethylenes (XLPE)—one of the polymers used nowadays to manufacture the insulator layer—have been irradiated under oxidative conditions, at two different dose rates and at different aging doses. Gases emitted and consumed from the irradiated polymers were quantified to identify the primary processes happening in the materials and thus the interactions involved between the different molecules composing the formulated polymers

Contains fulltext : 238196.pdf (Publisher’s version ) (Open Access) BACKGROUND AND PURPOSE: The phase III FLAME trial (NCT01168479) showed an increase in five-year biochemical disease-free survival, with no significant increase in toxicity when adding a focal boost to external beam radiotherapy (EBRT) for localized prostate cancer [Kerkmeijer et al. JCO 2021]. The aim of this study was to investigate the association between delivered radiation dose to the anorectum and gastrointestinal (GI) toxicity (grade >/=2). MATERIAL AND METHODS: All patients in the FLAME trial were analyzed, irrespective of treatment arm. The dose-effect relation of the anorectal dose parameters (D2cm(3) and D50%) and GI toxicity grade >/=2 in four years of follow-up was assessed using a mixed model analysis for repeated measurements, adjusted for age, cardiovascular disease, diabetes mellitus, T-stage, baseline toxicity grade >/=1, hormonal therapy and institute. RESULTS: A dose-effect relation for D2cm(3) and D50% was observed with adjusted odds ratios of 1.17 (95% CI 1.13-1.21, p < 0.0001) and 1.20 (95% CI 1.14-1.25, p < 0.0001) for GI toxicity, respectively. CONCLUSION: Although there was no difference in toxicity between study arms, a higher radiation dose to the anorectum was associated with a statistically significant increase in GI toxicity following EBRT for prostate cancer. This dose-effect relation was present for both large and small anorectal volumes. Therefore, further increase in dose to the anorectum should be weighed against the benefit of focal dose escalation for prostate cancer.

International audience; The remediation of metal(loid) contaminated sites often requires the application of an amendment, such as biochar. Biochar is the product of biomass pyrolysis and has been shown to reduce soil acidity, immobilize metal(loid)s and thus ameliorate plant growth. The beneficial effects of biochar are usually higher at a higher dose. However, an excessive dose can have negative outcomes due to nutrient loss. The application of an amendment to the soil comes at a financial cost, especially if the contaminated area is large, and therefore the optimum dose must be determined. In addition, to overcome the cost of biochar application, the use of a plant with economic benefits, such as flax, can be a suitable option. In this context, a mesocosm study, on a former mining soil polluted by As and Pb was performed, using flax and biochar applied at increasing concentrations. Results showed an increase in soil pH and the immobilization of Pb with increasing biochar doses. These ameliorations led to better plant growth. A higher biochar dose increased plant growth up to a 3% application rate, from which point dry weight no longer increased.Metal(loid) concentrations decreased between 1 and 3% biochar, and then increased at higher doses. It can thus be concluded that with 3% biochar, soil properties are ameliorated, metal(loid)s are immobilized, and plant growth increases, and a higher biochar application rate does not bring about better outcomes. Therefore, a 3% biochar application dose seems to be the best application dose to improve soil conditions and plant growth at a lower cost.

A rostro-caudal gradient of uranium (U) in the brain has been suggested after its inhalation. To study the factors influencing this mapping, we first used 30-min acute inhalation at 56 mg/m3of the relatively soluble form UO4in the rat. These exposure parameters were then used as a reference in comparison with the other experimental conditions. Other groups received acute inhalation at different concentrations, repeated low dose inhalation of UO4(10 exposures) or acute low dose inhalation of the insoluble form UO2. At 24 h after the last exposure, all rats showed a brain U accumulation with a rostro-caudal gradient as compared to controls. However, the total concentration to the brain was greater after repeated exposure than acute exposure, demonstrating an accumulative effect. In comparison with the low dose soluble U exposure, a higher accumulation in the front of the brain was observed after exposure to higher dose, to insoluble particles and following repetition of exposures, thus demonstrating a dose effect and influences of solubility and repetition of exposures. In the last part, exposure to ultrafine U particles made it possible to show 24 h after exposure the presence of U in the brain according to a rostro-caudal gradient. Finally, the time-course after exposure to micronic or nanometric U particles has revealed greater residence times for nanoparticles.

The spacecraft during operation are exposed to the destructive effect of the space radiation. The components that do not have the necessary radiation tolerance in terms of the dose effect require the installation of additional radiation shielding. The report considers a design method that allows you to automatically create radiation shielding in a solid modeler software in the form of complex three-dimensional (3D) objects, taking into account the mass shielding already existing on the spacecraft.

We used three dose levels (Sham, 2 mA, and 4 mA) and two different electrode montages (unihemispheric and bihemispheric) to examine DOSE and MONTAGE effects on regional cerebral blood flow (rCBF) as a surrogate marker of neural activity, and on a finger sequence task, as a surrogate behavioral measure drawing on brain regions targeted by transcranial direct current stimulation (tDCS). We placed the anodal electrode over the right motor region (C4) while the cathodal or return electrode was placed either over a left supraorbital region (unihemispheric montage) or over the left motor region (C3 in the bihemispheric montage). Performance changes in the finger sequence task for both hands (left hand: p = 0.0026, and right hand: p = 0.0002) showed a linear tDCS dose response but no montage effect. rCBF in the right hemispheric perirolandic area increased with dose under the anodal electrode (p = 0.027). In contrast, in the perirolandic ROI in the left hemisphere, rCBF showed a trend to increase with dose (p = 0.053) and a significant effect of montage (p = 0.00004). The bihemispheric montage showed additional rCBF increases in frontomesial regions in the 4mA condition but not in the 2 mA condition. Furthermore, we found strong correlations between simulated current density in the left and right perirolandic region and improvements in the finger sequence task performance (FSP) for the contralateral hand. Our data support not only a strong direct tDCS dose effect for rCBF and FSP as surrogate measures of targeted brain regions but also indirect effects on rCBF in functionally connected regions (e.g., frontomesial regions), particularly in the higher dose condition and on FSP of the ipsilateral hand (to the anodal electrode). At a higher dose and irrespective of polarity, a wider network of sensorimotor regions is positively affected by tDCS.

Background and purpose Anatomical changes during the stereotactic body radiation therapy (SBRT) of early stage non-small cell lung cancer (NSCLC) may cause the delivered dose to deviate from the planned dose. We investigate if normal tissue complication probability (NTCP) models based on the delivered dose predict radiation-induced rib fractures better than models based on the planned dose. Material and methods 437 NSCLC patients treated to a median dose of 3x18 Gy were included. Delivered dose was estimated by accumulating EQD2-corrected fraction doses after being deformed with daily CBCT-to-planning CT deformable image registration. Dosimetric parameters D x (dose to a relative volume x) were extracted for each rib included in the CBCTs field-of-view. An NTCP model was constructed for both planned and delivered dose, optimizing the parameters TD50 (dose with 50% toxicity risk), m (steepness of the curve) and x, using maximum likelihood estimation. Best NTCP model was determined using Akaike weights (Aw). Differences between the models were tested for significance using the Vuong’s test. Results Median time to fracture of 110 fractured ribs was 22.5 months. The maximum rib dose, D 0 , best predicted fractures for both planned and delivered dose. The average delivered D 0 was significantly lower than planned (p D 0 was the best, with Aw = 0.95. The models were not significantly different. Conclusion Delivered maximum dose to the ribs was significantly lower than planned. The NTCP model based on delivered dose improved predictions of radiation-induced rib fractures but did not reach statistical significance.

The clinical phenotype of celiac disease varies considerably among patients and the dosage of HLA-DQ2.5 alleles has been suggested to be a contributing factor. We investigated whether HLA-DQ2.5 allele dosage is associated with distinct clinical parameters at the time of diagnosis and with patients&rsquo, response to a gluten-free diet. The final cohort included 605 carefully phenotyped non-related Finnish celiac disease patients grouped as having 0, 1 or 2 copies of HLA-DQ2.5. Clinical data at the time of diagnosis and during gluten-free diet were collected systematically from medical records and supplementary interviews. An increasing HLA-DQ2.5 dose effect was detected for celiac disease antibody positivity at diagnosis (p = 0.021) and for the presence of any first-degree relatives with celiac disease (p = 0.011 and p = 0.031, respectively). Instead, DQ2.5-negative patients were suffering most often from classical symptoms at diagnosis (p = 0.007 between HLA groups). In addition, during follow-up they were most often symptomatic despite a gluten-free diet (p = 0.002 between groups). Our results thus suggest that increasing HLA-DQ2.5 dose only has a minor effect on the clinical picture of celiac disease. However, HLA-DQ2.5-negative patients should not be overlooked in clinical practice and particular attention should be paid to this patient group during gluten-free diet.

Advances in drug vapor exposure systems have enabled evaluation of Δ-9-tetrahydrocannabinol (THC) vapor effects in laboratory animals. The purpose of this study was to 1) establish a range of parameters of THC vapor exposure in rats sufficient to produce a behavioral dose-effect curve in a battery of tasks sensitive to THC; and 2) to investigate sex differences in the effects of THC vapor exposure and THC injection (intraperitoneal, IP) on these behaviors in two strains of outbred rats. Male and female Sprague Dawley and Wistar rats (N=22, 5-6/sex per group) received THC via passive vapor exposure (200mg/mL; 5 conditions) and IP injection (1-20mg/kg) in a within subject design. The effects of vaped and injected THC on appetite was determined using progressive ratio responding for food pellets. THC effects on nociception, measured using the tail withdrawal assay, and body temperature were also assessed during a 5-h test period for evaluation of time course of effects. Plasma THC concentrations were assessed after THC vapor and 10mg/kg IP THC. THC vapor produced exposure-related increases and decreases in motivation to obtain food under the progressive ratio schedule. IP THC (3-20mg/kg) reduced breakpoints. Vaped and injected THC produced exposure and dose-dependent antinociception and hypothermia. Sex and strain differences in THC effects were also observed. Plasma THC concentrations were higher after 10mg/kg IP THC (152ng/mL) compared to the highest vapor exposure condition tested (38ng/mL), but magnitude of behavioral effects were comparable. THC vapor exposure produced reliable, dose orderly effects on food-maintained behavior, nociception, and body temperature that are comparable to effects of IP THC, although there were differences in the time course of behavioral outcomes.

Aim: To evaluate the effect of the initial dose of poractant alfa on clinical outcomes in neonatal respiratory distress syndrome (RDS) and to assess adherence to treatment guidelines recommending a dose of 200 mg/kg.Methods: Records of neonates who received poractant alfa with a less invasive technique (LISA) or with the INtubate-SURfactant-Extubate (INSURE) technique were retrieved from the aggregated datasets of three prospective RDS studies conducted between 2015 and 2019. The impact of poractant dose on neonatal outcomes was analyzed by multivariate logistic regression. The primary endpoint was the need for early (Results: Of 994 eligible infants, 574 received poractant alfa with LISA, and 420 received poractant with INSURE. A logistic regression model using data from all 994 infants showed that the surfactant dose had a significant effect on reducing the need for MV and retreatment; the respective odds ratios were 0.92 (95% CI: 0.90–0.95) and 0.93 (95% CI: 0.90–0.96) per 10-mg/kg dose increment of poractant alfa. This dose effect was observed across all gestational age ranges and in infants treated with LISA. In newborns treated with INSURE, the dose of surfactant only influenced the rates of retreatment (p = 0.036) but not MV (p = 0.170). No impact on other neonatal outcomes was observed. In the subset of infants who received high (N = 502) and low (N = 58) doses of poractant, the high-dose group had lower rates of MV (34 vs. 48%, p = 0.042) and lower rates of retreatment (11 vs. 21%, p = 0.045). Surfactant underdosage increased with gestational age and ranged from a minimum of −3 mg/kg in 32 weeks.Conclusions: The initial dose of poractant alfa significantly impacts the need for invasive ventilation and retreatment. More mature newborns are at a greater risk of underdosing.

In this work, we demonstrate the use of a scatterometry-based technique to accurately monitor the dose variations seen on an EUV scanner. By carefully setting up the exposure conditions and data analysis, we can separate scanner-driven dose effects, mask reflectivity changes and process variations into its individual components. These measurements have a very high repro and throughput allowing us to use this technique to both monitor and provide active feedback to improve overall EUV cluster stability. We have used this technique to achieve a day-to-day dose variation of +-0.5% over a 6-month period on the NXE:3400B at IMEC.