Application of Deep Neural Networks as a Prescreening Tool to Assign Individualized Absorption Models in Pharmacokinetic Analysis

A specific model for drug absorption is necessarily assumed in pharmacokinetic (PK) analyses following extravascular dosing. Unfortunately, an inappropriate absorption model may force other model parameters to be poorly estimated. An added complexity arises in population PK analyses when different individuals appear to have different absorption patterns. The aim of this study is to demonstrate that a deep neural network (DNN) can be used to prescreen data and assign an individualized absorption model consistent with either a first-order, Erlang, or split-peak process. Ten thousand profiles were simulated for each of the three aforementioned shapes and used for training the DNN algorithm with a 30% hold-out validation set. During the training phase, a 99.7% accuracy was attained, with 99.4% accuracy during in the validation process. In testing the algorithm classification performance with external patient data, a 93.7% accuracy was reached. This algorithm was developed to prescreen individual data and assign a particular absorption model prior to a population PK analysis. We envision it being used as an efficient prescreening tool in other situations that involve a model component that appears to be variable across subjects. It has the potential to reduce the time needed to perform a manual visual assignment and eliminate inter-assessor variability and bias in assigning a sub-model.

Limits on absorption from a 332-MHz survey for fast radio bursts

ABSTRACT Fast radio bursts (FRBs) are bright, extragalactic radio pulses whose origins are still unknown. Until recently, most FRBs have been detected at frequencies greater than 1 GHz with a few exceptions at 800 MHz. The recent discoveries of FRBs at 400 MHz from the Canadian Hydrogen Intensity Mapping Experiment (CHIME) telescope have opened up possibilities for new insights about the progenitors while many other low-frequency surveys in the past have failed to find any FRBs. Here, we present results from an FRB survey recently conducted at the Jodrell Bank Observatory at 332 MHz with the 76-m Lovell telescope for a total of 58 d. We did not detect any FRBs in the survey and report a 90${{\ \rm per\ cent}}$ upper limit of 5500 FRBs per day per sky for a Euclidean Universe above a fluence threshold of 46 Jy ms. We discuss the possibility of absorption as the main cause of non-detections in low-frequency (<800 MHz) searches and invoke different absorption models to explain the same. We find that Induced Compton Scattering alone cannot account for absorption of radio emission and that our simulations favour a combination of Induced Compton Scattering and Free-Free Absorption to explain the non-detections. For a free–free absorption scenario, our constraints on the electron density are consistent with those expected in the post-shock region of the ionized ejecta in superluminous supernovae.

Intestinal Permeability and Drug Absorption: Predictive Experimental, Computational and In Vivo Approaches

The main objective of this review is to discuss recent advancements in the overall investigation and in vivo prediction of drug absorption. The intestinal permeability of an orally administered drug (given the value Peff) has been widely used to determine the rate and extent of the drug’s intestinal absorption (Fabs) in humans. Preclinical gastrointestinal (GI) absorption models are currently in demand for the pharmaceutical development of novel dosage forms and new drug products. However, there is a strong need to improve our understanding of the interplay between pharmaceutical, biopharmaceutical, biochemical, and physiological factors when predicting Fabs and bioavailability. Currently, our knowledge of GI secretion, GI motility, and regional intestinal permeability, in both healthy subjects and patients with GI diseases, is limited by the relative inaccessibility of some intestinal segments of the human GI tract. In particular, our understanding of the complex and highly dynamic physiology of the region from the mid-jejunum to the sigmoid colon could be significantly improved. One approach to the assessment of intestinal permeability is to use animal models that allow these intestinal regions to be investigated in detail and then to compare the results with those from simple human permeability models such as cell cultures. Investigation of intestinal drug permeation processes is a crucial biopharmaceutical step in the development of oral pharmaceutical products. The determination of the intestinal Peff for a specific drug is dependent on the technique, model, and conditions applied, and is influenced by multiple interactions between the drug molecule and the biological membranes.

Energy analysis of an electric furnace with a vibration hearth for roasting vermiculite concentrates

An energy analysis of an electric furnace with a vibration hearth using previously obtained analytical absorption models and a new, refined model of vermiculite heat assimilation is presented. The temperature-time equation, the formulas of the productivity of the furnace unit and the specific energy intensity of the calcination of vermiculite concentrates are obtained. It is shown that the new concept furnaces have a specific energy intensity of not more than 77.8 mJ/m3, which is more than three times lower than the energy intensity of fiery furnaces for roasting vermiculite. Ill. 4. Ref. 14.