A strategic behavioral-based intelligent transport system with artificial immune system

This paper presents a distributed control framework based on human immunity to manage, coordinate and schedule a fleet of agents employed in an automated transport system. Through the study of immunology, each agent is abstracted as an independent agent operating in a multi-agent system that carries local information, searches for solution space and exhibits robust behavior to accomplish tasks. The internal behaviors of the AIS agents, which are decided by their perception of the environment, are studied to describe their strategies in performing various operations. Simulations are presented to examine the significance of each behavioral state in every necessary action or step and the impacts of these states on the overall performance of the transport system. The results of the simulations illustrate the importance of each behavioral state and their inter-relationship in establishing a truly decentralized and non-deterministic transport system. © 2004 IEEE.published_or_final_versio

A decentralized control framework for modular robots

Distributed control paradigm offers robustness, scalability, and simplicity to the control and organization of module based systems. MSR (Modular Self-Reconfigurable) robot is a class of robot that best demonstrate the effectiveness of distributed systems as all modules in the robot are individuals that perform their own actuation and computation; the behavior of the complete robot is a collective behavior of all independent modules. In this paper, a general control framework, named General Suppression Framework, is proposed and a distributed control system based on the framework is presented. The control system is designed to control a set of MSR robots configured into a planar manipulator arm. All modules in the manipulator arm contain their own processing and actuation units, which allow them to evaluate and react to the environment independently. The modules can perform passive communication with their immediate neighbors and can exhibit aggressive or tolerant behavior based on the environment change to generate emergent group behaviors. A simulation program is developed to demonstrate the effectiveness of the distributed system in controlling the module based planar manipulator arm.published_or_final_versio

Cost-effectiveness simulation and analysis of colorectal cancer screening in Hong Kong Chinese population: comparison amongst colonoscopy, guaiac and immunologic fecal occult blood testing

Background: The aim of this study was to evaluate the cost-effectiveness of CRC screening strategies from the healthcare service provider perspective based on Chinese population. Methods: A Markov model was constructed to compare the cost-effectiveness of recommended screening strategies including annual/biennial guaiac fecal occult blood testing (G-FOBT), annual/biennial immunologic FOBT (I-FOBT), and colonoscopy every 10 years in Chinese aged 50 year over a 25-year period. External validity of model was tested against data retrieved from published randomized controlled trials of G-FOBT. Recourse use data collected from Chinese subjects among staging of colorectal neoplasm were combined with published unit cost data ($USD in 2009 price values) to estimate a stage-specific cost per patient. Quality-adjusted life-years (QALYs) were quantified based on the stage duration and SF-6D preference-based value of each stage. The cost-effectiveness outcome was the incremental cost-effectiveness ratio (ICER) represented by costs per life-years (LY) and costs per QALYs gained. Results: In base-case scenario, the non-dominated strategies were annual and biennial I-FOBT. Compared with no screening, the ICER presented$20,542/LYs and $3155/QALYs gained for annual I-FOBT, and$19,838/LYs gained and $2976/QALYs gained for biennial I-FOBT. The optimal screening strategy was annual I-FOBT that attained the highest ICER at the threshold of$50,000 per LYs or QALYs gained. Conclusion: The Markov model informed the health policymakers that I-FOBT every year may be the most effective and cost-effective CRC screening strategy among recommended screening strategies, depending on the willingness-to-pay of mass screening for Chinese population. Trial registration: ClinicalTrials.gov Identifier NCT02038283published_or_final_versio

Homeless street children in Nepal : use of allostatic load to assess the burden of childhood adversity.

As challenges to child well-being through economic disadvantage, family disruption, and migration or displacement escalate world wide, the need for cross-culturally robust understanding of childhood adversity proportionately increases. Toward this end, developmental risk was assessed in four contrasting groups of 107 Nepali children ages 10–14 years that represent distinctive, common conditions in which contemporary children grow up. Relative cumulative burden (allostatic load) indexed by multiple dimensions of physical and psychosocial stress was ascertained among homeless street boys and three family-based groups, from poor urban squatter settlements, urban middle class, and a remote rural village. Biomarkers of stress and vulnerability to stress included growth status, salivary cortisol, antibodies to Epstein–Barr virus, acute phase inflammatory responses (alpha1-antichymotrypsin), and cardiovascular fitness and reactivity (flex heart rate and pressor response). Individual biomarkers of risk and allostatic load differed markedly among groups, were highest in villagers, and varied by components of allostatic load. Such data suggest a need for critical appraisal of homelessness and migration as a risk factor to youth, given prevailing local conditions such as rural poverty, and represents the only multidimensional study of childhood allostatic load and developmental risk in non-Western settings

Guidelines for resident training in veterinary clinical pathology. IV: Laboratory quality management—teaching domains, competencies, and suggested learning outcomes

BACKGROUND : The 2019 ASVCP Education Committee Forum for Discussion, presented at the annual ASVCP/ACVP meeting, identified a need to develop recommendations for teaching laboratory quality management principles in veterinary clinical pathology residency training programs. OBJECTIVES : To present a competency-based framework for teaching laboratory quality management principles in veterinary clinical pathology residency training programs, including entrustable professional activities (EPAs), domains of competence, individual competencies, and learning outcomes. METHODS : A joint subcommittee of the ASVCP Quality Assurance and Laboratory Standards (QALS) and Education Committees executed this project. A draft guideline version was reviewed by the ASVCP membership and shared with selected ACVP committees in early 2022, and a final version was voted upon by the full QALS and Education Committees in late 2022. RESULTS : Eleven domains of competence with relevant individual competencies were identified. In addition, suggested learning outcomes and resource lists were developed. Domains and individual competencies were mapped to six EPAs. CONCLUSIONS : This guideline presents a framework for teaching principles of laboratory quality management in veterinary clinical pathology residency training programs and was designed to be comprehensive yet practical. Guidance on pedagogical terms and possible routes of implementation are included. Recommendations herein aim to improve and support resident training but may require gradual implementation, as programs phase in necessary expertise and resources. Future directions include the development of learning milestones and assessments and consideration of how recommendations intersect with the American College of Veterinary Pathologists training program accreditation and certifying examination.http://www.wileyonlinelibrary.com/journal/vcphj2023Companion Animal Clinical Studie

Raman Spectroscopic Modeling Of T- Lymphocyte Activation And Detection Of Acute Renal Allograft Rejection

ABSTRACT RAMAN SPECTROSCOPIC MODELING OF T-LYMPHOCYTE ACTIVATION AND DETECTION OF ACUTE RENAL ALLOGRAFT REJECTION By KRISTIAN L. BROWN 2010 Advisor: Gregory Auner, PhD Major: Biomedical Engineering Degree: Doctor of Philosophy Despite the advances made in the area of kidney transplantation, the disparity between the demand and available donated organs remains a dominant and unresolved issue. Given the paucity of available renal allografts the preservation of existing grafts is vital. One factor that has negatively impacted renal allograft survival is acute rejection (AR). Traditionally, kidney transplant centers have used elevations in serum creatinine as a screening tool for detecting AR. However, with its diagnostic delay, low sensitivity, and low specificity, serum creatinine has proven to be an unreliable and problematic bio-marker. Acute rejection is an activated T lymphocyte driven process that leads to graft dysfunction and possible loss. The activation state of T lymphocytes is determined by the specific cell surface receptor composition present. A technologic tool that could resolve these receptor differences could detect T lymphocyte activation and thus provide a diagnostic modality for AR. Raman spectroscopy (RS), a laser-based technology that is able to characterize substances based on molecular vibrational signatures, represents this modality. Using T lymphocytes isolated from human peripheral blood and clean-catch urine we investigated three aspects of T lymphocyte activation using a modified RS system. First, we explored the sensitivity (the ability to detect activation) of a RS-based system by analyzing mixed lymphocyte reacted (MLR), Mitomycin C inactivated, and resting T lymphocytes at 785nm and 514.5nm wavelengths. Second, the specificity (the ability to distinguish T cells activated by different stimuli) of the system was determined by comparing the signatures of MLR and CD3/CD28-activated T lymphocytes. Third, we analyzed the biomolecular events that conveyed the spectral changes detected by RS. This was carried out by coupling RS analysis of Mitogen-activated T lymphocytes with antigen expression kinetic studies designed to quantify the intensity and timing of cell surface receptor up-regulation. We found that there were significant RS signature differences between the MLR and non-activated (inactivated and resting) T lymphocytes while there was only a trend toward difference seen between the resting and inactivated cellular populations. When analyzing MLR versus CD3/CD28-activated cells, both samples differed from the inactivated and resting groups and demonstrated differences in Raman shifts at multiple foci when compared to one another. Receptor expression kinetics of Mitogen-activated T lymphocytes analyzed at the early and late phases of activation showed differential antibody immuno-fluorescent intensity. This correlated to spectral differences at defined peaks. Moreover, when analyzing all forms of activation (i.e. MLR, CD3/CD28, or Mitogen) there were conserved and reproducible signature changes regardless of the mode of activation which supports the notion that there are receptor and receptor moiety changes that are required in all forms of T lymphocyte activation. This dissertation outlines the use of RS in the resolution and modeling of cell surface receptor differences that define T lymphocyte activation. The accurate detection of T lymphocyte activation within a biomatrix is the foundational step toward the development of a noninvasive tool capable of accurately detecting AR in real-time within the clinical setting

Cross-scale quality assessment of a mechanistic cation exchange chromatography model

Cation exchange chromatography (CEX) is an essential part of most monoclonal antibody (mAb) purification platforms. Process characterization and root cause investigation of chromatographic unit operations are performed using scale down models (SDM). SDM chromatography columns typically have the identical bed height as the respective manufacturing‐scale, but a significantly reduced inner diameter. While SDMs enable process development demanding less material and time, their comparability to manufacturing‐scale can be affected by variability in feed composition, mobile phase and resin properties, or dispersion effects depending on the chromatography system at hand. Mechanistic models can help to close gaps between scales and reduce experimental efforts compared to experimental SDM applications. In this study, a multicomponent steric mass‐action (SMA) adsorption model was applied to the scale‐up of a CEX polishing step. Based on chromatograms and elution pool data ranging from laboratory‐ to manufacturing‐scale, the proposed modeling workflow enabled early identification of differences between scales, for example, system dispersion effects or ionic capacity variability. A multistage model qualification approach was introduced to measure the model quality and to understand the model\u27s limitations across scales. The experimental SDM and the in silico model were qualified against large‐scale data using the identical state of the art equivalence testing procedure. The mechanistic chromatography model avoided limitations of the SDM by capturing effects of bed height, loading density, feed composition, and mobile phase properties. The results demonstrate the applicability of mechanistic chromatography models as a possible alternative to conventional SDM approaches

Institutional shared resources and translational cancer research

The development and maintenance of adequate shared infrastructures is considered a major goal for academic centers promoting translational research programs. Among infrastructures favoring translational research, centralized facilities characterized by shared, multidisciplinary use of expensive laboratory instrumentation, or by complex computer hardware and software and/or by high professional skills are necessary to maintain or improve institutional scientific competitiveness. The success or failure of a shared resource program also depends on the choice of appropriate institutional policies and requires an effective institutional governance regarding decisions on staffing, existence and composition of advisory committees, policies and of defined mechanisms of reporting, budgeting and financial support of each resource. Shared Resources represent a widely diffused model to sustain cancer research; in fact, web sites from an impressive number of research Institutes and Universities in the U.S. contain pages dedicated to the SR that have been established in each Center, making a complete view of the situation impossible. However, a nation-wide overview of how Cancer Centers develop SR programs is available on the web site for NCI-designated Cancer Centers in the U.S., while in Europe, information is available for individual Cancer centers. This article will briefly summarize the institutional policies, the organizational needs, the characteristics, scientific aims, and future developments of SRs necessary to develop effective translational research programs in oncology

The translation of cell-based therapies:clinical landscape and manufacturing challenges

Cell-based therapies have the potential to make a large contribution toward currently unmet patient need and thus effective manufacture of these products is essential. Many challenges must be overcome before this can become a reality and a better definition of the manufacturing requirements for cell-based products must be obtained. The aim of this study is to inform industry and academia of current cell-based therapy clinical development and to identify gaps in their manufacturing requirements. A total of 1342 active cell-based therapy clinical trials have been identified and characterized based on cell type, target indication and trial phase. Multiple technologies have been assessed for the manufacture of these cell types in order to facilitate product translation and future process development

Landscape of Manufacturing Process of ATMP Cell Therapy Products for Unmet Clinical Needs

Immune cell therapies have been studied in numerous clinical trials using Advanced Therapy Medicinal Products (ATMP) against a number of diseases having no or inadequate alternative therapies available, for example, various cancer types, cerebral stroke, cardiac infarction, severe autoimmune disorders, or chronic infections. Despite the enormous number of positive observation in ex vivo or animal studies, convincing results in clinical studies remain scanty. The chapter presents a survey and reveals that the manufacturing of immune cells especially for clinical trials is until today primarily performed using archaic, scarcely controlled, and incomparable processes and methods. A deeper characterization of ex vivo expanded immune cells is urgently needed not only on the level of a few receptors and ligands on the cell surface but also with respect to the ever-contained subtypes in an expanded immune cell population, the pattern of secreted effector molecules, and their amounts over time and influences from in vivo components on them