Statistical Analysis of Series of N-of-1 Trials Using SAS

The statistical analysis of series of n-of-1 trials in which the treatments are randomized in cycles within individuals is described. Version 9.4 (TS1M3) of the SAS software is used for the statistical analysis. The statistical methods demonstrated assume that the outcome variable is normally distributed. The examples presented are for a comparison between two treatments. Several methods appropriate for the estimation and inference on the overall treatment effect as well as on the individual treatment effects are compared and discussed

Statistical Analysis of Series of N-of-1 Trials Using R

The statistical analysis of series of n-of-1 trials in which the treatments were randomized in cycles is described. Version 3.2 of the R statistical software is used for the analysis. It is not guaranteed that older versions of the R software produce equal results to the ones presented. Some of the code presented here might not run on older versions of the R software. Therefore, versions of R equal or superior to version 3.2 are recommended when running the code presente

The Reaction-Diffusion Front for A+B→∅A+B \to\emptyset in One Dimension

We study theoretically and numerically the steady state diffusion controlled reaction $A+B\rightarrow\emptyset$, where currents $J$ of $A$ and $B$ particles are applied at opposite boundaries. For a reaction rate $\lambda$, and equal diffusion constants $D$, we find that when $\lambda J^{-1/2} D^{-1/2}\ll 1$ the reaction front is well described by mean field theory. However, for $\lambda J^{-1/2} D^{-1/2}\gg 1$, the front acquires a Gaussian profile - a result of noise induced wandering of the reaction front center. We make a theoretical prediction for this profile which is in good agreement with simulation. Finally, we investigate the intrinsic (non-wandering) front width and find results consistent with scaling and field theoretic predictions.Comment: 11 pages, revtex, 4 separate PostScript figure

Milk production in saanen goats treated with repeated low doses of intermediate-release insulin during early lactation

The effect of insulin administration on the productive responses of Saanen goats during early lactation was investigated. Ten of 20 adult females were subjected to subcutaneous administration of intermediate-acting insulin (0.14UI/kg body weight) at 2, 9, and 14 days postpartum. Milk yield was measured twice daily for 13 weeks and milk samples were collected to measure protein and fat contents. Plasma levels of progesterone, insulin, non-esterifies fatty acids, glucose and other metabolites were measured. Results showed a significantly increased effect of insulin treatment on the content of milk fat and protein; moreover, milk production in the first and second postpartum weeks were higher than control group. The peak of lactation in the insulin group was achieved one week earlier in comparison to the control group. In addition, the milk production rate showed lower persistency (milk yield 13 week/milk yield at peak) in the same group. During the first four weeks of postpartum, treated animals showed greater weight loss and higher non-esterified fatty acid concentration, whereas no effect was observed on the concentration of progesterone and other metabolites. The above results indicated that repeated administration of insulin in dairy goats during early lactation increase yield and qualitative components of milk, but has substantial consequences on animal productive rate and metabolic response

Cholesterol-functionalized carvedilol-loaded PLGA nanoparticles: anti-inflammatory, antioxidant, and antitumor effects

The inflammation has been identified as factor of tumor progression, which has increased the interest and use of molecules with anti-inflammatory and antioxidant activities in the cancer treatment. In this study, the antioxidant, anti-inflammatory, and antitumor potentials of carvedilol was explored in a different approach. The cholesterol (CHO) was investigated as facilitated agent in the action of carvedilol-loaded nanoparticles. Different formulations exhibited spherical and stable nanoparticle with mean diameter size < 250 nm. The cholesterol changed the copolymer-drug interactions and the encapsulation efficiency. The in vitro cancer study was performed using murine colorectal cancer cell line (CT-26) to observe the cell viability and apoptosis on MTS assay and flow cytometry, respectively. The experiments have demonstrated that cholesterol improved the performance of drug-loaded nanoparticles, which was much better than free drug. The in vivo inflammation peritonitis model revealed that carvedilol-loaded nanoparticles increased the level of glutathione and leukocyte migration mainly when the functionalized drug-loaded nanoparticles were tested, in a lower dose than the free drug. As hypothesized, the experimental data suggest that cholesterol-functionalized carvedilol-loaded PLGA nanoparticles can be a novel and promising approach in the inflammation-induced cancer therapy since showed anti-inflammatory, antioxidant, and antitumor effects.Graphical abstractRadiolog

Comparison of sodium content of meals served by independent takeaways using standard versus reduced holed salt shakers: cross-sectional study

Background Takeaway food has a relatively poor nutritional profile. Providing takeaway outlets with reduced-holed salt shakers is one method thought to reduce salt use in takeaways, but effects have not been formally tested. We aimed to determine if there was a difference in sodium content of standard fish and chip meals served by Fish & Chip Shops that use standard (17 holes) versus reduced-holed (5 holes) salt shakers, taking advantage of natural variations in salt shakers used. Methods We conducted a cross-sectional study of all Fish & Chip Shops in two local government areas (n = 65), where servers added salt to meals as standard practice, and salt shaker used could be identified (n = 61). Standard fish and chip meals were purchased from each shop by incognito researchers and the purchase price and type of salt shaker used noted. Sodium content of full meals and their component parts (fish, chips, and fish batter) was determined using flame photometry. Differences in absolute and relative sodium content of meals and component parts between shops using reduced-holed versus standard salt-shakers were compared using linear regression before and after adjustment for purchase price and area. Results Reduced-holed salt shakers were used in 29 of 61 (47.5 %) included shops. There was no difference in absolute sodium content of meals purchased from shops using standard versus reduced-holed shakers (mean = 1147 mg [equivalent to 2.9 g salt]; SD = 424 mg; p > 0.05). Relative sodium content was significantly lower in meals from shops using reduced-holed (mean = 142.5 mg/100 g [equivalent to 0.4 g salt/100 g]; SD = 39.0 mg/100 g) versus standard shakers (mean = 182.0 mg/100 g; [equivalent to 0.5 g salt/100 g]; SD = 68.3 mg/100 g; p = 0.008). This was driven by differences in the sodium content of chips and was extinguished by adjustment for purchase price and area. Price was inversely associated with relative sodium content (p < 0.05). Conclusions Using reduced-holed salt shakers in Fish & Chip Shops is associated with lower relative sodium content of fish and chip meals. This is driven by differences in sodium content of chips, making our results relevant to the wide range of takeaways serving chips. Shops serving higher priced meals, which may reflect a more affluent customer base, may be more likely to use reduced-holed shakers

Apoptosis in human liver carcinoma caused by gold nanoparticles in combination with carvedilol is mediated via modulation of MAPK/Akt/mTOR pathway and EGFR/FAAD proteins

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Maximizing the potency of oxaliplatin coated nanoparticles with folic acid for modulating tumor progression in colorectal cancer

One of the challenges of nanotechnology is to improve the efficacy of treatments for diseases, in order to reduce morbidity and mortality rates. Following this line of study, we made a nanoparticle formulation with a small size, uniform surfaces, and a satisfactory encapsulation coefficient as a target for colorectal cancer cells. The results of binding and uptake prove that using the target system with folic acid works: Using this system, cytotoxicity and cell death are increased when compared to using free oxaliplatin. The data show that the system maximized the efficiency of oxaliplatin in modulating tumor progression, increasing apoptosis and decreasing resistance to the drug. Thus, for the first time, our findings suggest that PLGA-PEG-FA increases the antitumor effectiveness of oxaliplatin by functioning as a facilitator of drug delivery in colorectal cancer.Radiolog

Reaction Front in an A+B -> C Reaction-Subdiffusion Process

We study the reaction front for the process A+B -> C in which the reagents move subdiffusively. Our theoretical description is based on a fractional reaction-subdiffusion equation in which both the motion and the reaction terms are affected by the subdiffusive character of the process. We design numerical simulations to check our theoretical results, describing the simulations in some detail because the rules necessarily differ in important respects from those used in diffusive processes. Comparisons between theory and simulations are on the whole favorable, with the most difficult quantities to capture being those that involve very small numbers of particles. In particular, we analyze the total number of product particles, the width of the depletion zone, the production profile of product and its width, as well as the reactant concentrations at the center of the reaction zone, all as a function of time. We also analyze the shape of the product profile as a function of time, in particular its unusual behavior at the center of the reaction zone

First-in-class Microbial Ecosystem Therapeutic 4 (MET4) in combination with immune checkpoint inhibitors in patients with advanced solid tumors (MET4-IO trial)

Background: The intestinal microbiome has been associated with response to immune checkpoint inhibitors (ICIs) in humans and causally implicated in ICI responsiveness in animal models. Two recent human trials demonstrated that fecal microbiota transplant (FMT) from ICI responders can rescue ICI responses in refractory melanoma, but FMT has specific limitations to scaled use.Patients and methods: We conducted an early-phase clinical trial of a cultivated, orally delivered 30-species microbial consortium (Microbial Ecosystem Therapeutic 4, MET4) designed for co-administration with ICIs as an alternative to FMT and assessed safety, tolerability and ecological responses in patients with advanced solid tumors.Results: The trial achieved its primary safety and tolerability outcomes. There were no statistically significant differences in the primary ecological outcomes; however, differences in MET4 species relative abundance were evident after randomization that varied by patient and species. Increases in the relative abundance of several MET4 taxa, including Enterococcus and Bifidobacterium, taxa previously associated with ICI responsiveness, were observed and MET4 engraftment was associated with decreases in plasma and stool primary bile acids.Conclusions: This trial is the first report of the use of a microbial consortium as an alternative to FMT in advanced cancer patients receiving ICI and the results justify the further development of microbial consortia as a therapeutic co-intervention for ICI treatment in cancer