A Comparative Evaluation of Mono-, Di- and Triglyceride of Medium Chain Fatty Acids by Lipid/Surfactant/Water Phase Diagram, Solubility Determination and Dispersion Testing for Application in Pharmaceutical Dosage Form Development

Purpose To compare physiochemical properties of mono-, diand triglycerides of medium chain fatty acids for development of oral pharmaceutical dosage forms of poorly water-soluble drugs using phase diagrams, drug solubility, and drug dispersion experiments. Methods Phase diagrams were prepared using a monoglyceride (glycerol monocaprylocaprate: Capmul MCM ® EP), a diglyceride (glycerol dicaprylate) and two triglycerides (glycerol tricaprylate

Ex situ seed banks and the IUCN Red List.

Extinct, or just extinct in the wild? Plants lost from in situ habitat, but represented in seed banks, are labelled extinct despite the potential for restoration. A change in the International Union for Conservation of Nature Red List definition of extinct in the wild is needed to improve the status and prospects of threatened plant species

Nontangential limits and Fatou-type theorems on post-critically finite self-similar sets

In this paper we study the boundary limit properties of harmonic functions on $\mathbb R_+\times K$, the solutions $u(t,x)$ to the Poisson equation $$\frac{\partial^2 u}{\partial t^2} + \Delta u = 0,$$ where $K$ is a p.c.f. set and $\Delta$ its Laplacian given by a regular harmonic structure. In particular, we prove the existence of nontangential limits of the corresponding Poisson integrals, and the analogous results of the classical Fatou theorems for bounded and nontangentially bounded harmonic functions.Comment: 22 page

Developing Intensity-Duration-Frequency (IDF) Curves From Satellite-Based Precipitation: Methodology and Evaluation

Given the continuous advancement in the retrieval of precipitation from satellites, it is important to develop methods that incorporate satellite-based precipitation data sets in the design and planning of infrastructure. This is because in many regions around the world, in situ rainfall observations are sparse and have insufficient record length. A handful of studies examined the use of satellite-based precipitation to develop intensity-duration-frequency (IDF) curves; however, they have mostly focused on small spatial domains and relied on combining satellite-based with ground-based precipitation data sets. In this study, we explore this issue by providing a methodological framework with the potential to be applied in ungauged regions. This framework is based on accounting for the characteristics of satellite-based precipitation products, namely, adjustment of bias and transformation of areal to point rainfall. The latter method is based on previous studies on the reverse transformation (point to areal) commonly used to obtain catchment-scale IDF curves. The paper proceeds by applying this framework to develop IDF curves over the contiguous United States (CONUS); the data set used is Precipitation Estimation from Remotely Sensed Information Using Artificial Neural Networks – Climate Data Record (PERSIANN-CDR). IDFs are then evaluated against National Oceanic and Atmospheric Administration (NOAA) Atlas 14 to provide a quantitative estimate of their accuracy. Results show that median errors are in the range of (17–22%), (6–12%), and (3–8%) for one-day, two-day and three-day IDFs, respectively, and return periods in the range (2–100) years. Furthermore, a considerable percentage of satellite-based IDFs lie within the confidence interval of NOAA Atlas 14

Low dose rituximab is no less effective for nephrotic syndrome measured by 12-month outcome

Objective: Rituximab is an effective treatment for children with steroid dependent or frequently relapsing nephrotic syndrome. The optimum dosing schedule for rituximab has not been established. We hypothesized that a single low dose of 375 mg/m2 would have comparable outcomes to higher doses in reducing the frequency of relapse and time to B cell reconstitution. Methods: We conducted a multicenter retrospective observational cohort study of children with steroid-sensitive frequently relapsing nephrotic syndrome. Data were extracted from clinical records including the dates of diagnosis, treatment, relapses, the use of concomitant immunosuppression, and lymphocyte subset profiling. Patients treated earlier received variable doses of rituximab, although typically two doses of 750 mg/m2. Later, patients received the current regimen of a single dose of 375 mg/m2. The primary outcome was an absence of clinically confirmed relapse 12 months following rituximab administration. Secondary outcomes were median time to relapse, probability of being relapse-free at 6 and 24 months and time to reconstitution of CD19+ B cells. Results: Sixty patients received 143 courses of rituximab. Seven different dosing regimen strategies were used, ranging between 375 and 750 mg/m2 per dose, with administration of 1–4 doses. There was no significant difference in event-free survival at 12 months between dosing strategies. The median time to reconstitution of B cells was not significantly different between groups. Conclusions: Use of a single low-dose regimen of rituximab in the management of frequently relapsing nephrotic syndrome does not affect the probability of relapse at 12 months or time to B cell reconstitution compared to a conventional higher dose

Loss of Androgen Receptor-Dependent Growth Suppression by Prostate Cancer Cells Can Occur Independently from Acquiring Oncogenic Addiction to Androgen Receptor Signaling

The conversion of androgen receptor (AR) signaling as a mechanism of growth suppression of normal prostate epithelial cells to that of growth stimulation in prostate cancer cells is often associated with AR mutation, amplification and over-expression. Thus, down-regulation of AR signaling is commonly therapeutic for prostate cancer. The E006AA cell line was established from a hormone naïve, localized prostate cancer. E006AA cells are genetically aneuploid and grow equally well when xenografted into either intact or castrated male NOG but not nude mice. These cells exhibit: 1) X chromosome duplication and AR gene amplification, although paradoxically not coupled with increased AR expression, and 2) somatic, dominant-negative Serine-599-Glycine loss-of-function mutation within the dimerization surface of the DNA binding domain of the AR gene. No effect on the growth of E006AA cells is observed using targeted knockdown of endogenous mutant AR, ectopic expression of wild-type AR, or treatment with androgens or anti-androgens. E006AA cells represent a prototype for a newly identified subtype of prostate cancer cells that exhibit a dominant-negative AR loss-of-function in a hormonally naïve patient. Such loss-of-function eliminates AR-mediated growth suppression normally induced by normal physiological levels of androgens, thus producing a selective growth advantage for these malignant cells in hormonally naïve patients. These data highlight that loss of AR-mediated growth suppression is an independent process, and that, without additional changes, is insufficient for acquiring oncogene addiction to AR signaling. Thus, patients with prostate cancer cells harboring such AR loss-of-function mutations will not benefit from aggressive hormone or anti-AR therapies even though they express AR protein

Evolution of surface gravity waves over a submarine canyon

The effects of a submarine canyon on the propagation of ocean surface waves are examined with a three-dimensional coupled-mode model for wave propagation over steep topography. Whereas the classical geometrical optics approximation predicts an abrupt transition from complete transmission at small incidence angles to no transmission at large angles, the full model predicts a more gradual transition with partial reflection/transmission that is sensitive to the canyon geometry and controlled by evanescent modes for small incidence angles and relatively short waves. Model results for large incidence angles are compared with data from directional wave buoys deployed around the rim and over Scripps Canyon, near San Diego, California, during the Nearshore Canyon Experiment (NCEX). Wave heights are observed to decay across the canyon by about a factor 5 over a distance shorter than a wavelength. Yet, a spectral refraction model predicts an even larger reduction by about a factor 10, because low frequency components cannot cross the canyon in the geometrical optics approximation. The coupled-mode model yields accurate results over and behind the canyon. These results show that although most of the wave energy is refractively trapped on the offshore rim of the canyon, a small fraction of the wave energy 'tunnels' across the canyon. Simplifications of the model that reduce it to the standard and modified mild slope equations also yield good results, indicating that evanescent modes and high order bottom slope effects are of minor importance for the energy transformation of waves propagating across depth contours at large oblique angles

Development of solid SEDDS, III: application of Acconon® C-50 and Gelucire® 50/13 as both solidifying and emulsifying agents for medium chain triglycerides

Solid self-emulsifying drug delivery systems (SEDDS) for medium chain triglycerides (Captex® 355, ABITEC) were developed using stearoyl polyoxyl glycerides (Acconon® C-50, ABITEC and Gelucire® 50/13, Gattefosse) as both solidifying and emulsifying agents. Different mixtures of the lipid and each solidifying agent were heated to 65ºC until homogenously mixed clear liquids were formed. Probucol was dissolved as the model drug. The molten mass was then filled into hard gelatin capsules, which upon cooling to room temperature converted to a solid mass inside capsules. The triglyceride could be incorporated into the system to a concentration as high as 80% w/w, still maintaining the solid or semisolid consistency of the system. Powder XRD, DSC, microscopy (cross-polarization and confocal fluorescence techniques), dispersion test and particle size analysis of the solid systems with, and without, drug were conducted to characterize different formulations. The solidifying agents maintained their crystallinity in solid systems, while the lipids were interspersed in between crystalline regions. The drug remained solubilized in the lipid phase. The formulations dispersed almost completely in 2 hours with particle size of the dispersed lipid in the range of 250 to 500 nm when the lipid content in the formulation was up to 50% w/w. Thus, a novel method of developing solid formulations of liquid triglycerides by incorporating lipids in stearoyl polyoxyl glycerides has been developed

'A greatest hits compilation of mental health support': A qualitative study of health professionals' perspectives of modular CBT in paediatric epilepsy services

OBJECTIVES: The primary aim of this qualitative study was to explore the views of health professionals, with little previous clinical mental health training, of an adapted modular cognitive-behavioral intervention (MATCH-ADTC) for common mental health problems in children and young people with epilepsy. METHODS: Healthcare Professionals (HCPs) and their supervisors were interviewed at the start (n = 23) and end (n = 15) of the six-month training period. The interviews were transcribed verbatim and analyzed using thematic analysis. RESULTS: Three higher order themes with sub-themes were identified: (1) strengths of the MATCH-ADTC content and manual; (2) expectations of the treatment; and (3) improving practice with MATCH-ADTC. Overall impressions of the training and treatment were largely positive, with HCPs viewing MATCH-ADTC as an acceptable treatment for the families that they worked with. HCPs highlighted some challenges in delivering an integrated service, particularly relating to the time commitment involved and their own confidence in delivering the intervention, as many participants did not have a mental health background. CONCLUSIONS: The findings suggested that the intervention and training was acceptable to HCPs working in pediatric epilepsy services, and confidence grew over the six-month training period. Further research is needed to understand how to best train, supervise, and support HCPs in pediatric epilepsy services to deliver mental health treatments