Multi-tiered Approach Research Articles

Regression Modeling Strategy for Prediction of AUC of Evogliptin, a Novel Dipeptidyl Peptidase IV Inhibitor in Humans, Using Single dose PK Data

Aim: To develop a limited regression model of evogliptin for prediction of AUC data for internal (within study) and external studies. Method: Regression analyses (linear/power/polynomial) were performed in multitiered approach using paired peak plasma concentration (Cmax) versus AUC data of evogliptin. For all models, correlation co-efficient (r) and root mean square error (%RMSE) were used in predicting internal/external data. Bland–Altman analysis was performed for all the models. Results: Limited power model showed highest predictability (r = >0.98 and ≤15.5% RMSE), followed by linear model (r = >0.98 and ≤20.5% RMSE) and polynomial (r = >0.96 and ≤27.0% RMSE). Bland–Altman plots confirmed acceptable bias and precision. Conclusion: Limited regression models were successfully developed for prediction of AUC of evogliptin.

Repurposed FDA-approved drugs targeting genes influencing aging can extend lifespan and healthspan in rotifers

Pharmaceutical interventions can slow aging in animals, and have advantages because their dose can be tightly regulated and the timing of the intervention can be closely controlled. They also may complement environmental interventions like caloric restriction by acting additively. A fertile source for therapies slowing aging is FDA approved drugs whose safety has been investigated. Because drugs bind to several protein targets, they cause multiple effects, many of which have not been characterized. It is possible that some of the side effects of drugs prescribed for one therapy may have benefits in retarding aging. We used computationally guided drug screening for prioritizing drug targets to produce a short list of candidate compounds for in vivo testing. We applied the virtual ligand screening approach FINDSITEcomb for screening potential anti-aging protein targets against FDA approved drugs listed in DrugBank. A short list of 31 promising compounds was screened using a multi-tiered approach with rotifers as an animal model of aging. Primary and secondary survival screens and cohort life table experiments identified four drugs capable of extending rotifer lifespan by 8–42%. Exposures to 1 µM erythromycin, 5 µM carglumic acid, 3 µM capecitabine, and 1 µM ivermectin, extended rotifer lifespan without significant effect on reproduction. Some drugs also extended healthspan, as estimated by mitochondria activity and mobility (swimming speed). Our most promising result is that rotifer lifespan was extended by 7–8.9% even when treatment was started in middle age.

Adherence to responsibility in organic dry food supply chains

PurposeThe purpose of this paper is to explore the sharing of sustainability and social responsibility-centric values along the export-oriented organic dry food supply chain (ODFSC) using an institutional lens.Design/methodology/approachTo understand the perceptions of the shared ethos of the organic food industry along the entire supply chain, the research employed a multi-tier qualitative approach using semi-structured interviews and observations. The study focussed on supply chain actors including farmers and traders from the Indian sub-continent, and traders and retailers based in Europe and North America.FindingsIsomorphism, brought about by the vertical channelling of consumer preferences and values resulted in a higher degree of responsibility within the industry. The responsibility-centric ethos of the supply chain affected the responsibility-orientation of the supply chain actors and their operations.Research limitations/implicationsThe research focused mainly on the ODFSC actors in Kerala, a state in India, and this focus of the research could be a significant limitation in generalizing the findings to the rest of the emerging economy context because of cultural and educational differences.Originality/valueLiterature lacks in the studies of sharing of responsibility-centric values in supply chains through an institutional lens and this investigation contributes to the scant literature on isomorphism, shared values and responsible supply chain management.

A Review of Bird Deterrents Used in Agriculture

Author(s): Rivadeneira, Paula; Kross, Sara; Navarro-Gonzalez, Nora; Jay-Russell, Michele | Abstract: Animal intrusion causes significant agricultural losses each year. Wild and domestic animals destroy crops by eating and trampling them, and can pose food safety risks due to the deposition of feces on or near the crops. Birds are one of the most challenging animals to keep out of agricultural fields. Growers try countless methods to deter them, including visual, auditory, tactile, and olfactory means. While some of these methods work some of the time, none provide stand-alone protection all the time. Recently there has been interest in developing technology-based solutions to deter nuisance birds in agricultural settings, while others are exploring more natural methods, including falconry. We provide a general overview of bird deterrent methods that are currently in use in agricultural settings, and explore options for novel methods. We found that very few independent scientific studies have been conducted to assess the efficacy of most bird deterrent methods. Ultimately, a multi-tiered approach using integrated pest management techniques will likely be most useful as it can be tailored to meet the needs of individual farmers.

Cognitive smart environment: an approach based on concept hierarchies and sensor data fusion

Sensor data fusion gathers technological solutions for collecting, classifying and combining data from multiple sensors in a smart environment for augmenting knowledge about the system and realising cognitive behaviours. The goal is to make effective the management of acquired data and to promote the realisation of cognitive systems which can sense the environment, reason, and properly (re)act for reaching some purposes. Anyway, the development of such systems asks for suitable approaches able to deal with issues like heterogeneity, sensor/actuator management, system reactivity, behavioural modelling, and context awareness. This paper proposes a multi-tier approach, based on concept hierarchies and sensor data fusion, dealing with the above aspects. The approach favours separation of concerns and abstractions. It relies on the use of the agent metaphor and statecharts. The iSapiens platform is suggested for implementation purposes. As a significant case study, the development of a smart museum located in Cosenza (Italy) is proposed.

Mobile Data Collector Routing Protocol Scheme for Scalable Dense Wireless Sensor Network to Optimize Node’s Life

Wireless Sensor Networks (WSN) is a special kind of network communication architecture which has a very wide range of application and the cost-effectiveness of this architecture boosts its adaptability and usability. The erratic use of WSN, its rapid advancement has encouraged the research community to report several standing problems with WSN, among them is the concern of network life and node energy management in a dense network. This paper presents the experimental outcomes of using MDC multi-tier approach in dense network environments. Besides the node density, experiments also consider the inter-agricultural field hurdles that cause communication disturbance among the nodes that exist in ground level, or at some height above the farming field. The simulated experiment shows the noteworthy results, which comparatively enhance the network lifetime, efficiently utilizing individual node energy, and maximizing the content delivery.

Using Twitter to Energize the Introductory Statistics Class

In an effort to increase student learning in the introductory statistics class and simultaneously cater to their social media personas, an innovative pedagogical approach was developed using the social media platform Twitter. Our approach took advantage of over two decades’ worth of research findings regarding the established and successful pedagogical innovations in the teaching of statistics. By deploying a planned multi-tier approach that rests heavily on active learning strategies, we observed favorable outcomes from student learning, including active class participation, enhanced engagement and enjoyment, application of statistics concepts to everyday life, and aspects of improvement in statistical literacy, reasoning and thinking skills. This innovation used a combination of analytical writing, small group discussions, and Socratic discussion to accomplish these results.

Exceptional Professional Learning for RtI Implementation in Early Childhood Settings

Response to Intervention (RtI) is a multi-tiered problem-solving approach that has been used to help struggling school-aged children and is now proposed as a promising evidence-based model for early childhood settings. Successful implementation of RtI may require early childhood practitioners to develop new skills in assessment, intervention, and data-based decision making. Since these individuals may not receive formal training in the aforementioned areas, providing effective professional development may be a critical element needed to address these challenges. Unfortunately, there continues to be little emphasis on professional development for early childhood RtI implementation despite the clear need for such services. This article proposes a professional development framework to address RtI implementation in early childhood settings.

Evaluación del desarrollo socio-económico mediante la clasificación de países: Un análisis cluster de América Latina y el Caribe (ALC) y la Unión Europea (EU)

The aim of this paper is to provide an assessment of socio-economic development through a multi-tiered approach relying both on traditional and modern understanding and the measuring of human development. A systematic approach is adopted to classify countries using a non-hierarchical clustering method. Three macro-scenarios are considered – classical, modern and extended – which contrast information regarding inequality, poverty and the quality of employment with the role of education, health, institutions and environmental sustainability. Our approach is based on new estimates of inequality and poverty that are derived from Atkinson’s Pareto interpolation, which bridges the discrepancy between national income accounts and household surveys. This may serve to offset the statistical bias in the estimates of incomeinequality and poverty, and to better interpret national and regional socioeconomic performance. The analysis is carried out in a comparative framework between the Latin America and the Caribbean (LAC) region and the European Union (EU).

A novel multi-tiered experimental approach unfolding the mechanisms behind cyclodextrin-vitamin inclusion complexes for enhanced vitamin solubility and stability

This study was conducted to provide a mechanistic account for understanding the synthesis, characterization and solubility phenomena of vitamin complexes with cyclodextrins (CD) for enhanced solubility and stability employing experimental and in silico molecular modeling strategies. New geometric, molecular and energetic analyses were pursued to explicate experimentally derived cholecalciferol complexes. Various CD molecules (α-, β-, γ-, and hydroxypropyl β-) were complexed with three vitamins: cholecalciferol, ascorbic acid and α-tocopherol. The Inclusion Efficiency (IE%) was computed for each CD-vitamin complex. The highest IE% achieved for a cholecalciferol complex was for ‘βCDD3-8’, after utilizing a unique CD:cholecalciferol molar synthesis ratio of 2.5:1, never before reported as successful. 2HPβCD-cholecalciferol, γCD-cholecalciferol and α-tocopherol inclusion complexes (IC's) reached maximal IE% with a CD:vitamin molar ratio of 5:1. The results demonstrate that IE%, thermal stability, concentration, carrier solubility, molecular mechanics and intended release profile are key factors to consider when synthesizing vitamin-CD complexes. Phase-solubility data provided insights into the design of formulations with IC's that may provide analogous oral vitamin release profiles even when hydrophobic and hydrophilic vitamins are co-incorporated. Static lattice atomistic simulations were able to validate experimentally derived cholecalciferol IE phenomena and are invaluable parameters when approaching formulation strategies using CD's for improved solubility and efficacy of vitamins.

Creating Suicide Safety in Schools: A public health suicide prevention program in New York State

Suicide is a serious public health problem worldwide. The World Health Organization calls for collaboration among all sectors of society using a multi-tiered approach to address risk factors. Schools have played a central public health role in fighting infectious diseases, malnutrition, community violence, accidental injuries, and heart disease. Similarly, when it comes to youth suicide prevention, schools are critically important community institutions.Schools are central civic institutions for building the resilience and positive helping environment necessary for the prevention of suicide. In this paper we will describe a program called “Creating Suicide Safety in Schools” (CSSS), which was developed to address the need for more comprehensive and consistentsuicide prevention training for school settings. The CSSS provides aframework for integrating school-based suicide prevention best practices, and the program is being implemented and evaluated in New York State. We will outline the CSSS model, the workshop, and how it is disseminated. The CSSS Workshop has been offered to school personnel for more than five years andindividuals from several hundred schools have participated in this training opportunity. Preliminary findings of the program’s acceptability in terms of attitudes, knowledge, perceptions of administrative support, and sense of empowerment based on a survey of 93 participants, will be presented.

An effect-directed strategy for characterizing emerging chemicals in food contact materials made from paper and board

Food contact materials (FCM) are any type of item intended to come into contact with foods and thus represent a potential source for human exposure to chemicals. Regarding FCMs made of paper and board, information pertaining to their chemical constituents and the potential impacts on human health remains scarce, which hampers safety evaluation. We describe an effect-directed strategy to identify and characterize emerging chemicals in paper and board FCMs. Twenty FCMs were tested in eight reporter gene assays, including assays for the AR, ER, AhR, PPARγ, Nrf2 and p53, as well as mutagenicity. All FCMs exhibited activities in at least one assay. As proof-of-principle, FCM samples obtained from a sandwich wrapper and a pizza box were carried through a complete step-by-step multi-tiered approach. The pizza box exhibited ER activity, likely caused by the presence of bisphenol A, dibutyl phthalate, and benzylbutyl phthalate. The sandwich wrapper exhibited AR antagonism, likely caused by abietic acid and dehydroabietic acid. Migration studies confirmed that the active chemicals can transfer from FCMs to food simulants. In conclusion, we report an effect-directed strategy that can identify hazards posed by FCMs made from paper and board, including the identification of the chemical(s) responsible for the observed activity.

A panel of 130 autosomal single-nucleotide polymorphisms for ancestry assignment in five Asian populations and in Caucasians.

Ancestry informative single-nucleotide polymorphism (AISNP) panels for differentiating between East and Southeast Asian populations are scarce. This study aimed to identify AISNPs for ancestry assignment of five East and Southeast Asian populations, and Caucasians. We analyzed 145 autosomal SNPs of the 627 DNA samples from individuals of six populations (234 Taiwanese Han, 91 Filipinos, 79 Indonesians, 60 Thais, 71 Vietnamese, and 92 Caucasians) using arrays. The multiple logistic regression model and a multi-tier approach were used for ancestry classification. We observed that 130 AISNPs were effective for classifying the ethnic origins with fair accuracy. Among the 130 AISNPs, 122 were useful for stratification between these five Asian populations and 64 were effective for differentiating between Caucasians and these Asian populations. For differentiation between Caucasians and Asians, an accuracy rate of 100% was achieved in these 627 subjects with 50 optimal AISNPs among the 64 effective SNPs. For classification of the five Asian populations, the accuracy rates of ancestry inference using 20 to 57 SNPs for each of the two Asian populations ranged from 74.1% to 100%. Another 14 degraded DNA samples with incomplete profiling were analyzed, and the ancestry of 12 (85.7%) of those subjects was accurately assigned. We developed a 130-AISNP panel for ethnic origin differentiation between the five East and Southeast Asian populations and Caucasians. This AISNP set may be helpful for individual ancestral assignment of these populations in forensic casework.

Neural stem cell transplantation in ischemic stroke: A role for preconditioning and cellular engineering

Ischemic stroke continues to be a leading cause of morbidity and mortality throughout the world. To protect and/or repair the ischemic brain, a multitiered approach may be centered on neural stem cell (NSC) transplantation. Transplanted NSCs exert beneficial effects not only via structural replacement, but also via immunomodulatory and/or neurotrophic actions. Unfortunately, the clinical translation of such promising therapies remains elusive, in part due to their limited persistence/survivability within the hostile ischemic microenvironment. Herein, we discuss current approaches for the development of NSCs more amenable to survival within the ischemic brain as a tool for future cellular therapies in stroke.

Liver transplantation for severe alcoholic hepatitis-The CON view.

In patients with severe alcoholic hepatitis (AH) who have failed medical therapy, liver transplantation (LT) remains a controversial therapeutic option. This is exemplified by the fact that most of these patients will not have had a period of abstinence prior to consideration for transplantation. Both abstinence before transplantation and the duration of abstinence are important predictors of post-transplant relapse. Furthermore, relapse after transplantation has been associated with accelerated graft injury and increase mortality. Recent pilot studies have demonstrated a benefit in short-term survival with early transplantation in highly selected small number of patients compared to matched controls. The results of these studies raises the possibility of extending graft allocation to these subjects. Despite stringent assessment and a multi-tiered approach to selecting out patients for transplantation, the relapse rate was not insignificant at 12%. As the long-term outcome remains unclear, further relapses with time can still occur. These studies also highlight the fact that the overwhelming majority of subjects with severe AH who are non-responsive to medical therapy are not suitable for LT. Indeed, further large-scale multicentre prospective studies with long-term follow-up are required to confirm the preliminary findings.

β-Aminoalcohols as Potential Reactivators of Aged Sarin-/Soman-Inhibited Acetylcholinesterase

Organophosphate nerve agents inhibit the enzyme acetylcholinesterase (AChE), which is involved in nerve signal transduction, by forming covalent adducts with its catalytic serine residue. AChE adducts with soman and sarin nerve agents undergo dealkylation, a process known as aging, within a few minutes and a few hours, respectively. This transformation is detrimental because it precludes reactivation of AChE with known oxime-based antidotes. Here, we designed a β-aminoalcohol molecule for aged AChE reactivation, using a multi-tiered computational approach. This approach includes high-quality quantum mechanical/molecular mechanical calculations, providing reliable reactivation steps and energetics. The calculations suggest that the designed β-aminoalcohol can selectively reactivate aged sarin-/soman-inhibited AChE. Furthermore, unlike existing antidotes, the designed β-aminoalcohol lacks a permanent charge, making it potentially active in the central nervous system. The mechanistic insights of this study can help guide the development of new AChE reactivators with improved access to the central nervous system.

Efficient Cancer Detection Using Multiple Neural Networks.

The inspection of live excised tissue specimens to ascertain malignancy is a challenging task in dermatopathology and generally in histopathology. We introduce a portable desktop prototype device that provides highly accurate neural network classification of malignant and benign tissue. The handheld device collects 47 impedance data samples from 1 Hz to 32 MHz via tetrapolar blackened platinum electrodes. The data analysis was implemented with six different backpropagation neural networks (BNN). A data set consisting of 180 malignant and 180 benign breast tissue data files in an approved IRB study at the Aurora Medical Center, Milwaukee, WI, USA, were utilized as a neural network input. The BNN structure consisted of a multi-tiered consensus approach autonomously selecting four of six neural networks to determine a malignant or benign classification. The BNN analysis was then compared with the histology results with consistent sensitivity of 100% and a specificity of 100%. This implementation successfully relied solely on statistical variation between the benign and malignant impedance data and intricate neural network configuration. This device and BNN implementation provides a novel approach that could be a valuable tool to augment current medical practice assessment of the health of breast, squamous, and basal cell carcinoma and other excised tissue without requisite tissue specimen expertise. It has the potential to provide clinical management personnel with a fast non-invasive accurate assessment of biopsied or sectioned excised tissue in various clinical settings.

Preservice early childhood teachers’ perceived effects on competence of dealing with social emotional challenging behavior of young children by taking early childhood social education class with multi-tiered approach

Preservice early childhood teachers’ perceived effects on competence of dealing with social emotional challenging behavior of young children by taking early childhood social education class with multi-tiered approach

An Organic Anion Transporter 1 (OAT1)-centered Metabolic Network

There has been a recent interest in the broader physiological importance of multispecific "drug" transporters of the SLC and ABC transporter families. Here, a novel multi-tiered systems biology approach was used to predict metabolites and signaling molecules potentially affected by the in vivo deletion of organic anion transporter 1 (Oat1, Slc22a6, originally NKT), a major kidney-expressed drug transporter. Validation of some predictions in wet-lab assays, together with re-evaluation of existing transport and knock-out metabolomics data, generated an experimentally validated, confidence ranked set of OAT1-interacting endogenous compounds enabling construction of an "OAT1-centered metabolic interaction network." Pathway and enrichment analysis indicated an important role for OAT1 in metabolism involving: the TCA cycle, tryptophan and other amino acids, fatty acids, prostaglandins, cyclic nucleotides, odorants, polyamines, and vitamins. The partly validated reconstructed network is also consistent with a major role for OAT1 in modulating metabolic and signaling pathways involving uric acid, gut microbiome products, and so-called uremic toxins accumulating in chronic kidney disease. Together, the findings are compatible with the hypothesized role of drug transporters in remote inter-organ and inter-organismal communication: The Remote Sensing and Signaling Hypothesis (Nigam, S. K. (2015) Nat. Rev. Drug Disc. 14, 29). The fact that OAT1 can affect many systemic biological pathways suggests that drug-metabolite interactions need to be considered beyond simple competition for the drug transporter itself and may explain aspects of drug-induced metabolic syndrome. Our approach should provide novel mechanistic insights into the role of OAT1 and other drug transporters implicated in metabolic diseases like gout, diabetes, and chronic kidney disease.

Take a multitiered approach to control residence hall access

Living in residence halls presents opportunities for students to engage with the campus and take part in learning opportunities outside the classroom. But residence halls also present safety challenges. “This is the most critical area we want to keep safe,” said Rhonda L. Harris, assistant vice president of public safety and chief of police at Old Dominion University in Virginia.