Study Design and Data Analysis of Artificial Pancreas Device Systems with Closed-Loop Glucose-Sensing Insulin Delivery

Objective: The objective of this article is to provide a high-profile review and discussion on the study design and statistical analysis of pivotal clinical trials conducted to demonstrate the safety and effectiveness of closed-loop investigational artificial pancreas device systems (APDSs) in premarket approval applications. Methods: The United States Food and Drug Administration (FDA) guidance on the content of investigational device exemption and premarket approval applications for APDSs is reviewed with special emphasis on study design and statistical analysis of the pivotal clinical trials. The two pivotal studies for the MiniMed 670G hybrid closed-loop system by Medtronic in their premarket approval application are summarized and discussed. Results: The United States FDA established detailed recommendations on the study design and statistical analysis of pivotal clinical trials for the industry that seek market investigational APDSs and for FDA scientific reviewers that regulate the device applications. The recommendations cover specifics regarding patient population, clinical endpoints, and strategies for data analysis. However, the two pivotal studies that demonstrated the effectiveness of the FDA-approved MiniMed 670G hybrid closed-loop system were not typical randomized controlled trials as per FDA recommendations. Conclusion: The development and regulation of investigational APDSs require careful and sophisticated clinical study designs and data analysis in premarket approval applications. The regulatory evaluation process of the APDSs is rather complicated since the devices consist of multiple components that collaboratively function to mimic human pancreases

Fungicidal Control of Downy Mildew of Pearl Millet

Among the three fungicides tested in vitro against Sclerospora graminicola, metalaxyl and oxadixyl were effective in completely inhibiting sporangial production and germination at 250 ppm concentration. With mancozeb, complete inhibition of sporangial production was observed only at 1000 ppm concentration while there was no complete inhibition of sporangial germination even at 1000 ppm. In a field trial conducted during the kharif season of 1985, metalaxyl 25 WP seed treatment protected the pearl millet crop from downy mildew upto 30 days. Seed treatment followed by one foliar spray with metalaxyl or mancozeb was more effective than seed treatment alone. Seed treatment with metalaxyl followed by a single combined foliar spray of metalaxyl + mancozeb was superior to seed treatment with metalaxyl followed by a single foliar spray of either of these fungicides

Significance of phosphate nano-fertilizers foliar application : a brief real-field study of quantitative, physiological parameters, and agro-ecological diversity in sunflower

SUPPLEMENTARY MATERIALS : FIGURE S1: X-ray diffraction powder patterns of hydroxylapatite formed from Sheelavati fish bone; FIGURE S2: X-ray diffraction powder patterns the mixture of parascholzite and calcium zinc phosphate (nano/macro-ZnPhos) formed by chemical co-precipitation method; TABLE S1: Basic values of electrical conductivity and the pH of applied nano-fertilizers compared to applied water as a control variant; TABLE S2: Comparison of monthly temperature and precipitation characteristics during the vegetation season of 2022 with the longterm norm from 1991 to 2020; TABLE S3: Abundance and dominance of the Coleoptera family in the studied treatments with sunflower at the Nitra-Dolná Malanta locality during vegetation season 2022. TABLE S4: Abundance and dominance of the Carabidae species in the studied treatments with sunflower at the Nitra-Dolná Malanta locality during vegetation season of 2022.One of the challenges in agriculture practices is guaranteeing an adequate and bioavailable phosphorus supply for plants on phosphorus-deficient soils. A promising alternative lies in the utilization of phosphate nano-fertilizers (NFs) through spray applications. Therefore, this short-term study aimed to investigate the yet undetermined widespread impact of P-NFs on crops characterized by broad leaves, an intensive rate of photosynthesis, and belonging to the oilseed plant, sunflower (Helianthus annuus L.). To achieve this, NFs were applied at lower concentrations of various phosphatebased NFs, including (i) nano-hydroxylapatite (nano-Hap) and (ii) a mixture of nano-calcium zinc phosphate and macro-sized parascholzite (nano/macro-ZnPhos), in comparison to the NF-free control. The study was carried out under authentic field conditions during the 2022 vegetation season at the Dolná Malanta site within the Central European Region. The empirical evidence presented herein indicates that the utilization of biocompatible and bioactive nano-Hap, initially engineered for biomedical applications, and nano/macro-ZnPhos, now foliarly applied at reduced concentrations, elicited a statistically significant elevation in quantitative parameters and seasonal physiological responses. The parameters analyzed included head diameter, dry head weight, seed yield per hectare, nutritional seed oiliness, etc. as well as the physiological normalized difference vegetation index (NDVI), stomatal conductance index (Ig), and crop water stress index (CWSI). In terms of agro-ecological terrestrial bio/diversity, it was evident that the nano/macro-ZnPhos was the most hospitable variant for the terrestric insect community, but surprisingly, the agronomically more popular nano-Hap showed only statistically insignificant changes in the diversity of the detected communities. However, the relevance of outcomes highlighted using nano-fertilizers, supporting the concept of precision and sustainable agriculture under field conditions.The Grant Agency of the Slovak Republic Ministry of Education, the Slovak Academy of Sciences, and by the European Union foundation (Erasmus Plus Programme for academic staff mobility) and postgraduate program sponsored by the National Scholarship Programme of the Slovak Republic trough SAIA Organization.https://www.mdpi.com/journal/agronomyam2024ChemistrySDG-15:Life on lan

Human Peripheral Blood Mononuclear Cells Exhibit Heterogeneous CD52 Expression Levels and Show Differential Sensitivity to Alemtuzumab Mediated Cytolysis

Alemtuzumab is a monoclonal antibody that targets cell surface CD52 and is effective in depleting lymphocytes by cytolytic effects in vivo. Although the cytolytic effects of alemtuzumab are dependent on the density of CD52 antigen on cells, there is scant information regarding the expression levels of CD52 on different cell types. In this study, CD52 expression was assessed on phenotypically distinct subsets of lymphoid and myeloid cells in peripheral blood mononuclear cells (PBMCs) from normal donors. Results demonstrate that subsets of PBMCs express differing levels of CD52. Quantitative analysis showed that memory B cells and myeloid dendritic cells (mDCs) display the highest number while natural killer (NK) cells, plasmacytoid dendritic cells (pDCs) and basophils have the lowest number of CD52 molecules per cell amongst lymphoid and myeloid cell populations respectively. Results of complement dependent cytolysis (CDC) studies indicated that alemtuzumab mediated profound cytolytic effects on B and T cells with minimal effect on NK cells, basophils and pDCs, correlating with the density of CD52 on these cells. Interestingly, despite high CD52 levels, mDCs and monocytes were less susceptible to alemtuzumab-mediated CDC indicating that antigen density alone does not define susceptibility. Additional studies indicated that higher expression levels of complement inhibitory proteins (CIPs) on these cells partially contributes to their resistance to alemtuzumab mediated CDC. These results indicate that alemtuzumab is most effective in depleting cells of the adaptive immune system while leaving innate immune cells relatively intact

SocialTagger- Collaborative Tagging for Blogs in the Long Tail

Social bookmarking is the process through which users share tags for online resources like blogs with others. Such collaborative tags provide valuable metadata for retrieval systems. While the successes of collaborative tagging systems have been demonstrated by popular websites like Del.icio.us, these sites cover only a small fraction of the available blogs on the web. The vast majority of the blogs are not available on any collaborative tagging system and are often tagged only by the authors. This lack of coverage of collaborative tags is a considerable roadblock in using the tag metadata in a web scale information retrieval system. To solve this problem we propose and implement a system to automatically recommend collaborative tags for a blog. The automatically generated tags will help to surface the blogs by making them available on social book marking sites and allow them to be easily discovered and potentially further tagged by a wider population