A model-based approach using GSK3772847, an anti-interleukin-33 receptor monoclonal antibody, as a showcase to predict SC administration PK and free target dynamics based on PK and total target measurements after IV administration.

Integrated modeling of the pharmacokinetic (PK) and target binding, by means of a TMDD model, can provide valuable insights into the expected pharmacodynamic (PD) effects of monoclonal antibodies (mAbs). Optimal characterization of the human PK and target binding for mAbs requires data obtained after intravenous (IV) administration which can be combined with subcutaneous (SC) data to further this characterization. Integration of free and/or total target measurements in a population TMDD model will allow quantification of target engagement which is the first step in the cascade leading to efficacy.

Two new user-friendly methods to assess pharmacometric parameter identifiability on categorical and continuous scales.

Parameter identifiability methods assess whether the parameters of a model are uniquely determined by the observations. While the success of a model fit can provide some information on this, it can be valuable to determine identifiability before any fit has been attempted, or to separate identifiability from other issues. Two concepts that lean themselves well for identifiability analysis and have been underutilized are the sensitivity matrix (SM) and the Fisher information matrix (FIM).

Navigating the landscape of parameter identifiability methods: A workflow recommendation for model development.

In pharmacometric modeling, it is often important to know whether the data is sufficiently rich to identify the parameters of a proposed model. While it may be possible to assess this based on the results of a model fit, it is often difficult to disentangle identifiability issues from other model fitting and numerical problems. Furthermore, it can be of value to ascertain identifiability beforehand.

Pharmacokinetics and pharmacodynamics of finerenone in patients with chronic kidney disease and type 2 diabetes: Insights based on FIGARO-DKD and FIDELIO-DKD.

Aims: To perform dose-exposure-response analyses to determine the effects of finerenone doses.

Materials And Methods: Two randomized, double-blind, placebo-controlled phase 3 trials enrolling 13 026 randomized participants with type 2 diabetes (T2D) from global sites, each with an estimated glomerular filtration rate (eGFR) of 25 to 90 mL/min/1.73 m , a urine albumin-creatinine ratio (UACR) of 30 to 5000 mg/g, and serum potassium ≤ 4.

Longitudinal efficacy and safety modeling and simulation framework to aid dose selection of belantamab mafodotin for patients with multiple myeloma.

Belantamab mafodotin, a monomethyl auristatin F (MMAF)-containing monoclonal antibody-drug conjugate (ADC), demonstrated deep and durable responses in the DRiving Excellence in Approaches to Multiple Myeloma (DREAMM)-1 and pivotal DREAMM-2 studies in patients with relapsed/refractory multiple myeloma. As with other MMAF-containing ADCs, ocular adverse events were observed. To predict the effects of belantamab mafodotin dosing regimens and dose-modification strategies on efficacy and ocular safety end points, DREAMM-1 and DREAMM-2 data across a range of doses were used to develop an integrated simulation framework incorporating two separate longitudinal models and the published population pharmacokinetic model.

Bread Products from Blends of African Climate Resilient Crops: Baking Quality, Sensory Profile and Consumers' Perception.

With food insecurity rising dramatically in Sub-Saharan Africa, promoting the use of sorghum, cowpea and cassava flours in staple food such as bread may reduce wheat imports and stimulate the local economy through new value chains. However, studies addressing the technological functionality of blends of these crops and the sensory properties of the obtained breads are scarce. In this study, cowpea varieties (i.

Effect of Bioprocessing on Techno-Functional Properties of Climate-Resilient African Crops, Sorghum and Cowpea.

Sorghum and cowpea are very compatible for intercropping in hot and dry environments, and they also have complementary nutritional compositions. Thus, the crops have the potential to improve food security in regions threatened by climate change. The aim of this study was to investigate different enzymes (carbohydrate-degrading, proteases and phytases) and lactic acid bacteria (LAB) fermentation to improve the techno-functional properties of sorghum and cowpea flours.

Towards the creation of personalized bakery products using 3D food printing.

Bakery products with interesting color, shape and texture have been created using 3D food printing. Current research focuses on the development of new formulations and the optimization of the printing and post-printing treatment processes, in order to obtain high-quality 3D-printed bakery products. Knowledge about food rheology is useful for the development of dough formulations with good 3D-printability.

Dose-Exposure-Response Analysis of the Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone on UACR and eGFR: An Analysis from FIDELIO-DKD.

Background And Objective: Finerenone reduces the risk of kidney failure in patients with chronic kidney disease and type 2 diabetes. Changes in the urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) are surrogates for kidney failure. We performed dose-exposure-response analyses to determine the effects of finerenone on these surrogates in the presence and absence of sodium glucose co-transporter-2 inhibitors (SGLT2is) using individual patient data from the FIDELIO-DKD study.

Towards Sustainable Shifts to Healthy Diets and Food Security in Sub-Saharan Africa with Climate-Resilient Crops in Bread-Type Products: A Food System Analysis.

Massive urbanization and increasing disposable incomes favor a rapid transition in diets and lifestyle in sub-Saharan Africa (SSA). As a result, the SSA population is becoming increasingly vulnerable to the double burden of malnutrition and obesity. This, combined with the increasing pressure to produce sufficient food and provide employment for this growing population together with the threat of climate change-induced declining crop yields, requires urgent sustainable solutions.

Designing Mechanical Properties of 3D Printed Cookies through Computer Aided Engineering.

Additive manufacturing or 3D printing can be applied in the food sector to create food products with personalized properties such as shape, texture, and composition. In this article, we introduce a computer aided engineering (CAE) methodology to design 3D printed food products with tunable mechanical properties. The focus was on the Young modulus as a proxy of texture.

Mechanism-based modeling of the effect of a novel inhibitor of vascular adhesion protein-1 on albuminuria and renal function markers in patients with diabetic kidney disease.

The vascular adhesion protein-1 (VAP-1) inhibitor ASP8232 reduces albuminuria in patients with type 2 diabetes and chronic kidney disease. A mechanism-based model was developed to quantify the effects of ASP8232 on renal markers from a placebo-controlled Phase 2 study in diabetic kidney disease with 12 weeks of ASP8232 treatment. The model incorporated the available pharmacokinetic, pharmacodynamic (plasma VAP-1 concentration and activity), serum and urine creatinine, serum cystatin C, albumin excretion rate, urinary albumin-to-creatinine ratio, and urine volume information in an integrated manner.

Can cyclist safety be improved with intelligent transport systems?

In recent years, Intelligent Transport Systems (ITS) have assisted in the decrease of road traffic fatalities, particularly amongst passenger car occupants. Vulnerable Road Users (VRUs) such as pedestrians, cyclists, moped riders and motorcyclists, however, have not been that much in focus when developing ITS. Therefore, there is a clear need for ITS which specifically address VRUs as an integrated element of the traffic system.

Difference in postprandial GLP-1 response despite similar glucose kinetics after consumption of wheat breads with different particle size in healthy men.

Purpose: Underlying mechanisms of the beneficial health effects of low glycemic index starchy foods are not fully elucidated yet. We varied the wheat particle size to obtain fiber-rich breads with a high and low glycemic response and investigated the differences in postprandial glucose kinetics and metabolic response after their consumption.

Methods: Ten healthy male volunteers participated in a randomized, crossover study, consuming C-enriched breads with different structures; a control bread (CB) made from wheat flour combined with wheat bran, and a kernel bread (KB) where 85 % of flour was substituted with broken wheat kernels.

The structure of wheat bread influences the postprandial metabolic response in healthy men.

Postprandial high glucose and insulin responses after starchy food consumption, associated with an increased risk of developing several metabolic diseases, could possibly be improved by altering food structure. We investigated the influence of a compact food structure; different wheat products with a similar composition were created using different processing conditions. The postprandial glucose kinetics and metabolic response to bread with a compact structure (flat bread, FB) was compared to bread with a porous structure (control bread, CB) in a randomized, crossover study with ten healthy male volunteers.

Reduced-Sodium Lunches Are Well-Accepted by Uninformed Consumers Over a 3-Week Period and Result in Decreased Daily Dietary Sodium Intakes: A Randomized Controlled Trial.

Background: Processed foods are major contributors to excessive sodium intake in Western populations. We investigated the effect of food reformulation on daily dietary sodium intake.

Objective: To determine whether uninformed consumers accept reduced-sodium lunches and to determine the effect of consuming reduced-sodium lunches on 24-hour urinary sodium excretion.

A salt reduction of 50% in bread does not decrease bread consumption or increase sodium intake by the choice of sandwich fillings.

Bread is a major contributor to sodium intake in many countries. Reducing the salt (NaCl) content in bread might be an effective way to reduce overall sodium intake. The objectives of this study were to examine the effects of gradually lowering the salt content in brown bread, with and without flavor compensation (KCl and yeast extract), on bread consumption and sodium intake compensation by choice of sandwich fillings.