Maturity Continuum Research Articles

Single-cell proteomics and transcriptomics capture eosinophil development and identify the role of IL-5 in their lineage transit amplification

The activities, ontogeny, and mechanisms of lineage expansion of eosinophils are less well resolved than those of other immune cells, despite the use of biological therapies targeting the eosinophilia-promoting cytokine interleukin (IL)-5 or its receptor, IL-5Rα. We combined single-cell proteomics and transcriptomics and generated transgenic IL-5Rα reporter mice to revisit eosinophilopoiesis. We reconciled human and murine eosinophilopoiesis and provided extensive cell-surface immunophenotyping and transcriptomes at different stages along the continuum of eosinophil maturation. We used these resources to show that IL-5 promoted eosinophil-lineage expansion via transit amplification, while its deletion or neutralization did not compromise eosinophil maturation. Informed from our resources, we also showed that interferon response factor-8, considered an essential promoter of myelopoiesis, was not intrinsically required for eosinophilopoiesis. This work hence provides resources, methods, and insights for understanding eosinophil ontogeny, the effects of current precision therapeutics, and the regulation of eosinophil development and numbers in health and disease.

AI Maturity Continuum: A Three Step Framework to Understand Return On Investment (ROI) in AI

AI Maturity Continuum: A Three Step Framework to Understand Return On Investment (ROI) in AI

Proposal for a Maturity Continuum Model for Open Research Data

As a contribution to the general effort in research to generalize and improve the practices of Open Research Data (ORD), we developed a model conceptualizing the degrees of maturity of a research community in terms of ORD. This model may be used to assess the ORD capacity or maturity level of a specific research community, to strengthen the use of standards with respect to ORD within this community, and to increase its ORD maturity level.
 We present the background and our motivations for developing such an instrument as well as the reasoning leading to its design. We present its elements in detail and discuss possible applications.

Assessment resistance: using Kubler-Ross to understand and respond

Purpose Faculty participation in the assurance of learning (AoL) is requisite both for the effective operation of the system and for accreditation compliance, but faculty often resist engaging in AoL tasks. The purpose of this paper is to provide specific recommendations to address faculty concerns and to guide AoL systems toward maturity. Design/methodology/approach This paper provides a comprehensive model of faculty resistance perspectives aligned to AoL maturity, provides specific responses to faculty resistance and introduces success markers of progress toward maturity. Findings Specifically, a three-stage model of AoL system maturity is presented and aligned with five faculty perspectives. For each faculty perspective, responses targeting causal factors are proposed and signs of progress toward the next level of faculty engagement are highlighted. Practical implications Faculty and AoL leaders will be able to identify their current stage of AoL system maturity and implement practical solutions to move to the next stage of system maturity. Social implications Understanding the motivations for faculty resistance will facilitate more meaningful and effective internal interactions as a school seeks to improve its AoL system. In turn, a more effective AoL system will promote better learning experiences for students; and better learning allows students to become productive in their chosen careers more quickly, thus improving society as a whole. Originality/value To the knowledge, no prior paper has organized faculty resistance along a maturity continuum, provided targeted responses based on the level of maturity or included signs that indicate growth toward the next level of maturity.

Comprehensive phenotyping of erythropoiesis in human bone marrow: Evaluation of normal and ineffective erythropoiesis.

Identification of stage-specific erythroid cells is critical for studies of normal and disordered human erythropoiesis. While immunophenotypic strategies have previously been developed to identify cells at each stage of terminal erythroid differentiation, erythroid progenitors are currently defined very broadly. Refined strategies to identify and characterize BFU-E and CFU-E subsets are critically needed. To address this unmet need, a flow cytometry-based technique was developed that combines the established surface markers CD34 and CD36 with CD117, CD71, and CD105. This combination allowed for the separation of erythroid progenitor cells into four discrete populations along a continuum of progressive maturation, with increasing cell size and decreasing nuclear/cytoplasmic ratio, proliferative capacity and stem cell factor responsiveness. This strategy was validated in uncultured, primary erythroid cells isolated from bone marrow of healthy individuals. Functional colony assays of these progenitor populations revealed enrichment of BFU-E only in the earliest population, transitioning to cells yielding BFU-E and CFU-E, then CFU-E only. Utilizing CD34/CD105 and GPA/CD105 profiles, all four progenitor stages and all five stages of terminal erythroid differentiation could be identified. Applying this immunophenotyping strategy to primary bone marrow cells from patients with myelodysplastic syndrome, identified defects in erythroid progenitors and in terminal erythroid differentiation. This novel immunophenotyping technique will be a valuable tool for studies of normal and perturbed human erythropoiesis. It will allow for the discovery of stage-specific molecular and functional insights into normal erythropoiesis as well as for identification and characterization of stage-specific defects in inherited and acquired disorders of erythropoiesis.

Genesis of solid bitumen

This paper presents a new schematic model for generation and timing of multiple phases of solid bitumen throughout the continuum of organic matter maturation in source and tight reservoir rocks. Five distinct stages in the evolution of solid bitumen are proposed: (1) diagenetic solid bitumen (or degraded bituminite), which is not a secondary maceral resulting from the thermal cracking of kerogen. Instead it is derived from degradation of bituminite in the diagenesis stage (Ro < 0.5%); (2) initial-oil solid bitumen, is a consolidated form of early catagenetically generated bitumen at the incipient oil window (Ro ~ 0.5–0.7%); (3) primary-oil solid bitumen is derived from thermally generated bitumen and crude oil in the primary oil window (Ro ~ 0.7–1.0%); (4) late-oil solid bitumen (solid-wax) is derived from the waxy bitumen separated from the mature paraffinic heavy oil in the primary- and late-oil windows; and (5) pyrobitumen, which is mainly a non-generative solid bitumen, is evolved from thermal cracking of the remaining hydrocarbon residue and other types of solid bitumen in the dry gas window and higher temperature (Ro > 1.4%). This model shows concurrence of multi-populations solid bitumen with oil, bitumen, and other phases of fluid hydrocarbon residue during most of the maturity continuum.

Single-Cell Mapping of Progressive Fetal-to-Adult Transition in Human Naïve T Cells

Whereas the human fetal immune system is poised to generate immune tolerance and suppress inflammation in utero, an adult-like immune system emerges to orchestrate anti-pathogen immune responses in post-natal life. It has been posited that cells of the adult immune system arise as a discrete ontological “layer” of hematopoietic stem-progenitor cells (HSPCs) and their progeny; evidence supporting this model in humans has, however, been inconclusive. Here, we combine bulk and single-cell transcriptional profiling of lymphoid, myeloid, and HSPCs from fetal, perinatal, and adult developmental stages to demonstrate that the fetal-to-adult transition occurs progressively along a continuum of maturity — with a substantial degree of interindividual variation at the time of birth — rather than via a transition between discrete waves. These findings have important implications in the design of strategies for prophylaxis against infection in the newborn, and for the use of umbilical cord blood (UCB) in the setting of transplantation.

Molecular heterogeneity in pyrogenic dissolved organic matter from a thermal series of oak and grass chars

Pyrogenic organic matter (Py-OM), generated via the incomplete combustion of biomass, is well studied due to the presence of slow-cycling, condensed aromatic compounds (ConAC) known to sequester in soils and sediments. Recently, dissolved Py-OM (Py-DOM) has received interest, due to its higher mobility and potential to be transferred through watersheds to aquatic systems. Py-DOM quantities, molecular identities and importance to global carbon budgets and cycles are only beginning to be understood. Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) analyses were performed on Py-DOM isolated from oak and grass biochars produced over a range of temperatures (250–650 °C), and the data are compared to complementary 1H NMR spectroscopic and benzenepolycarboxylic acid biomarker (BPCAs) analyses. Py-DOM is revealed to be a heterogeneous mixture of compounds ranging in relative aromaticity and oxygenation. FTICR-MS analyses demonstrate a decrease in Py-DOM relative oxygen content and a concurrent increase in aliphatic character and heteroatomic (N, Cl) content. 1H NMR and BPCAs analyses detail low O/C dissolved ConAC not observed by FTICR-MS, demonstrating the necessity for a multiple proxy approach to Py-DOM characterization. Heterogeneous Py-DOM is explained as resulting from pyrolysis-initiated and radical-mediated functional group cleavage, aromatic condensation and aromatic ring-opening reactions. Oak biomass progresses faster along a char maturity continuum for a given pyrolysis temperature, perhaps due to its greater lignin content or radical quenching by grass cuticular material. Biomass species and pyrolysis temperature likely result in different Py-DOM compositions and fates and must be considered when evaluating the impacts of wildfires and biochar applications.

Single-Cell Mapping of Progressive Fetal-to-Adult Transition in Human Hematopoiesis

Whereas the human fetal immune system is poised to generate immune tolerance and suppress inflammation in utero, an adult-like immune system emerges to orchestrate anti-pathogen immune responses in post-natal life. It has been posited that cells of the adult immune system arise as a discrete ontological “layer” of hematopoietic stem-progenitor cells (HSPCs) and their progeny; evidence supporting this model in humans has, however, been inconclusive. Here, we combine bulk and single-cell transcriptional profiling of lymphoid, myeloid, and HSPCs from fetal, perinatal, and adult developmental stages to demonstrate that the fetal-to-adult transition occurs progressively along a continuum of maturity — with a substantial degree of interindividual variation at the time of birth — rather than via a transition between discrete waves. These findings have important implications in the design of strategies for prophylaxis against infection in the newborn, and for the use of umbilical cord blood (UCB) in the setting of transplantation.

Single cell RNA-sequencing reveals cellular heterogeneity and trajectories of lineage specification during murine embryonic limb development

The coordinated spatial and temporal regulation of gene expression in the murine hindlimb determines the identity of mesenchymal progenitors and the development of diversity of musculoskeletal tissues they form. Hindlimb development has historically been studied with lineage tracing of individual genes selected a priori, or at the bulk tissue level, which does not allow for the determination of single cell transcriptional programs yielding mature cell types and tissues. To identify the cellular trajectories of lineage specification during limb bud development, we used single cell mRNA sequencing (scRNA-seq) to profile the developing murine hindlimb between embryonic days (E)11.5-E18.5. We found cell type heterogeneity at all time points, and the expected cell types that form the mouse hindlimb. In addition, we used RNA fluorescence in situ hybridization (FISH) to examine the spatial locations of cell types and cell trajectories to understand the ancestral continuum of cell maturation. This data provides a resource for the transcriptional program of hindlimb development that will support future studies of musculoskeletal development and generate hypotheses for tissue regeneration.

Management Accounting Maturity Levels Continuum Model: a Conceptual Framework

Until now, in the financial domain, there were only few attempts made to develop maturity models – a useful tool to identify strengths and weaknesses of certain domains of an organization. The aim of this paper is to present a maturity model for management accounting. The method used to develop the model is an interpretive approach, in which an exploratory sequential mixed method research design was applied to broadly explore and understand data on management accounting systems in various settings and in its historical perspective. This study extends my previous research on development of management accounting and financial leadership (Lebedev, 2014, 2015, 2016, 2018, 2019b, 2019a). The framework traces 10 prototype roles of management accounting along their continuum of maturity (from “non-existent” to “strategic leadership”). Each maturity level reflects the extent to which management accounting creates value for its users based on the support provided for “conversations” among stakeholders, the deepness of leadership “embodied” into the management accounting function, and the effectiveness of management accounting principles and management accounting practices (MAPs) employed. This study contributes to the theory of management accounting by offering a framework for understanding of the evolution of financial function and management accounting. In practical terms, the results of the research could be applied to support decisions in transformation of financial function along its maturity continuum (both conducted internally by managers and/or with external support of consultants and advisors), supporting the process of reconciliation of current practices of a company being transformed to a proposed transformational strategy and chosen direction of implementation.

Evaluating Digital Maturity and Patient Acceptability of Real-Time Patient Experience Feedback Systems: Systematic Review.

BackgroundOne of the essential elements of a strategic approach to improving patients’ experience is to measure and report on patients’ experiences in real time. Real-time feedback (RTF) is increasingly being collected using digital technology; however, there are several factors that may influence the success of the digital system.ObjectiveThe aim of this review was to evaluate the digital maturity and patient acceptability of real-time patient experience feedback systems.MethodsWe systematically searched the following databases to identify papers that used digital systems to collect RTF: The Cochrane Library, Global Health, Health Management Information Consortium, Medical Literature Analysis and Retrieval System Online, EMBASE, PsycINFO, Web of Science, and CINAHL. In addition, Google Scholar and gray literature were utilized. Studies were assessed on their digital maturity using a Digital Maturity Framework on the basis of the following 4 domains: capacity/resource, usage, interoperability, and impact. A total score of 4 indicated the highest level of digital maturity.ResultsRTF was collected primarily using touchscreens, tablets, and Web-based platforms. Implementation of digital systems showed acceptable response rates and generally positive views from patients and staff. Patient demographics according to RTF responses varied. An overrepresentation existed in females with a white predominance and in patients aged ≥65 years. Of 13 eligible studies, none had digital systems that were deemed to be of the highest level of maturity. Three studies received a score of 3, 2, and 1, respectively. Four studies scored 0 points. While 7 studies demonstrated capacity/resource, 8 demonstrated impact. None of the studies demonstrated interoperability in their digital systems.ConclusionsPatients and staff alike are willing to engage in RTF delivered using digital technology, thereby disrupting previous paper-based feedback. However, a lack of emphasis on digital maturity may lead to ineffective RTF, thwarting improvement efforts. Therefore, given the potential benefits of RTF, health care services should ensure that their digital systems deliver across the digital maturity continuum.

Discrete-event simulation software selection for manufacturing based on the maturity model

The main objective of this research is to develop a new method to help an industry select the right DESS (discrete-event simulation software), which helps improve the productivity of a given process.This paper addresses this issue by developing a methodology that undertakes two aspects of the problem. First, it proposes a methodology that allows for companies to self-assess their current internal processes based on a maturity model to identify where they stand in the maturity continuum for simulation. Second, it applies the analytical hierarchical process (AHP) to support simulation software selection by detailing and weighting the components that are important for the specific company to meet its business objectives. To the best of our knowledge, there are no other studies that combine these two methodological tools to help decision making for DESS selection.

An HMM and polynomial regression based approach for remaining useful life and health state estimation of cutting tools

There has been considerable advances, over the last few decades, in sensing instrumentation, hardware, signal processing algorithms, and internet technology infrastructure that has eventually paved the way for long envisioned concept of smart factories under the concept of Industry 4.0. It has been projected that by 2020, somewhere from 26 to 50 billion “things” will be connected to the Internet. This will lead to astonishing amount of precise data in real time. To leverage on the collected data, factories across the globe is embracing digital manufacturing in the era of fourth industrial revolution, Industry 4.0. Combined with today’s more advanced analytics, these data enable industrial organizations to implement new, more effective maintenance strategies to progress further along on the maturity continuum from reactive, to preventive, to condition-based, to predictive, and – ultimately – to prescriptive maintenance. This instigate development of advanced analytic techniques to large scale deployment of conditioned based maintenance. We present a novel approach for health state estimation to facilitate autonomous diagnostics and thereupon we build our prognostics module based on the diagnostics result using a polynomial regression models. The proposed research presents a model based sequential clustering on time series sensor signals for estimating health states of a cutting tool. Results obtained validates the competitive performance of the method on a CNC machining test-bed outfitted with thrust-force and torque sensors for monitoring drill-bits.

Development of endothermy in birds: patterns and mechanisms.

Endothermy is a conspicuous and important adaptation in birds. Even though juvenile and adult birds are endothermic and maintain a constant, high body temperature by means of internal heat production, they begin life expressing an ectothermic phenotype. Depending on where a species falls along a continuum of maturity at hatching, from precocial to altricial, they begin to express endothermic traits either close to the time of hatching or as nestlings over a period of 1-3 weeks. Developing endothermy requires attaining a high basal metabolic rate and associated aerobic scope to produce sufficient internal heat, insulation to retain the internally produced heat, and a thermostat that "turns on" heat production in response to cooling ambient temperatures. To support the high metabolic costs of endothermy, the animal must have the capacity to deliver sufficient oxygen and nutrients to the heat-generating tissues. In this review, we examine the development of physiological and morphological traits that are required for endothermy and discuss their potential to limit the development of endothermy. These include ventilatory and cardiovascular function, contribution of visceral organ masses, membrane lipid composition, substrate supply pathways, and skeletal muscle physiology. The developmental trajectories of each of these systems in precocial and altricial species can have significant effects on the development of an endothermic phenotype.

Local Volatility Calibration by Optimal Transport

The calibration of volatility models from observable option prices is a fundamental problem in quantitative finance. The most common approach among industry practitioners is based on the celebrated Dupire's formula, which requires the knowledge of vanilla option prices for a continuum of strikes and maturities that can only be obtained via some form of price interpolation. In this paper, we propose a new local volatility calibration technique using the theory of optimal transport. We formulate a time continuous martingale optimal transport problem, which seeks a martingale diffusion process that matches the known densities of an asset price at two different dates, while minimizing a chosen cost function. Inspired by the seminal work of Benamou and Brenier, we formulate the problem as a convex optimization problem, derive its dual formulation, and solve it numerically via an augmented Lagrangian method and the alternative direction method of multipliers (ADMM) algorithm. The solution effectively reconstructs the dynamic of the asset price between the two dates by recovering the optimal local volatility function, without requiring any time interpolation of the option prices.

An enterprise risk management knowledge-based decision support system for construction firms

Purpose – The purpose of this paper is to develop a knowledge-based decision support system for enterprise risk management (KBDSS-ERM) for Chinese construction firms (CCFs) to facilitate their ERM implementation. The specific objectives of the KBDSS-ERM are: first, assess the ERM maturity in a CCF; second, visualize the ERM maturity assessment results; third, provide action plans for improving the ERM implementation along the maturity continuum; and finally, generate a printable ERM maturity assessment report. Design/methodology/approach – Microsoft Visual Studio 2010 was used to develop the KBDSS-ERM. Based on literature review and structured interviews, 191 action plans for improving ERM implementation were identified and included in the knowledge base. A fuzzy ERM maturity model, including 16 maturity criteria and 66 best practices, was embedded into the KBDSS-ERM. A total of ten experts from ten different CCFs, who were not involved in the survey or the development of the action plans, were invited to validate the KBDSS-ERM. Findings – The validation results indicated that the results of the KBDSS-ERM were consistent with the expert judgments, and that the KBDSS-ERM had the accuracy ranging from 92.9 to 83.7 percent in assessing the maturity criteria and the overall ERM maturity of CCFs. In addition, the experts recognized the KBDSS-ERM as being a robust, convenient and useful tool for ERM implementation in CCFs. Research limitations/implications – First, the maturity criteria and ERM best practices that were identified in this study may not be exhaustive even though close attention was paid in the research methodology adopted to circumvent this risk. Additionally, as the applicability of the best practices and the importance of the maturity criteria were checked in the context of CCFs, one should be cautious when the KBDSS-ERM is being applied in other construction firms outside of the CCFs domain. Practical implications – Using the KBDSS-ERM, the management can clearly understand its ERM implementation as well as the strengths and weaknesses, and obtain the action plans recommended by the KBDSS-ERM. Thus, with the information from the KBDSS-ERM, the management would make better decisions relating to ERM. In addition, while using the KBDSS-ERM, the staffs need to read the ERM best practices, which allows them to learn the ERM fundamentals and produce practical or innovative ideas relating to ERM. Thus, the KBDSS-ERM would contribute to the organizational learning of companies. Originality/value – The primary contribution is the provision of 191 specific action plans that could be followed to enhance ERM practice. These action plans are arguably the first to be presented for the construction industry and therefore add to existing knowledge of ERM, now embedded in the KBDSS. In addition, the KBDSS-ERM is also the first computerized ERM tool developed specifically for construction firms. Although the KBDSS-ERM is primarily designed for CCFs, the implications of this study are not limited to CCFs because researchers and practitioners could adopt the research method of this study to develop KBDSSs for other construction firms.

Forecasting the US Term Structure of Interest Rates Using Nonparametric Functional Data Analysis

In this paper we consider a novel procedure to forecasting the US zero coupon bond yields for a continuum of maturities by using the methodology of nonparametric functional data analysis (NP‐FDA). We interpret the US yields as curves since the term structure of interest rates defines a relation between the yield of a bond and its maturity. Within the NP‐FDA approach, each curve is viewed as a functional random variable and the dynamics present in the sample are modeled without imposing any parametric structure. In order to evaluate forecast the performance of the proposed estimator, we consider forecast horizons h = 1,3,6,12… months and the results are compared with widely known benchmark models. Our estimates with NP‐FDA present predictive performance superior to its competitors in many situations considered, especially for short‐term maturities. Copyright © 2016 John Wiley &amp; Sons, Ltd.

Robust No Arbitrage of the Second Kind with a Continuum of Assets and Proportional Transaction Costs

Motivated by bond markets with a continuum of possible maturities, we study a robust version of the absence of arbitrage opportunity of the second kind introduced by Rasonyi in a continuous-time and infinite-dimensional financial market model with proportional transaction costs.

Animal Modeling of Early Programming and Disruption of Pubertal Maturation.

Puberty is a fascinating developmental transition that gates the attainment of reproductive capacity and culminates the somatic and sexual maturation of the organism. Rather than a circumscribed phenomenon, puberty is the endpoint of a long-lasting developmental continuum, which initiates in utero. Besides important genetic determinants, the tempo of puberty is influenced by numerous endogenous and exogenous factors that, acting at different levels of the developing hypothalamic-pituitary-gonadal (HPG) axis along the maturational continuum indicated above, can influence puberty onset. Among the different modifiers of puberty, in this chapter we will focus our attention on two major groups of signals, sex steroids and nutritional cues, and how these interplay mostly with the central elements of the HPG axis, and especially with gonadotropin-releasing hormone neurons and their key upstream afferents, Kiss1 neurons, to influence the timing of puberty. Special emphasis will be given to summarize information emerging from relevant preclinical (mostly rodent) animal models, and how this information might be relevant in terms of translational medicine, as it may help for a better understanding and eventually management of pubertal disorders of escalating prevalence worldwide.