Integrated Product and Production Platforms for Pharmaceutical Products: Design Thinking for the Development of Personalized Medicines

Treatments, when customized according to individual patient attributes, are in recent yearsreferred to as personalized medicines. Personalized medicines aim at improving the therapeutic outcome of the patient. However, current pharmaceutical production is dominatedby mass production in a batch manner, i.e. producing large volumes of identical products.Uncertainties prevail regarding the ability of current production to respond to the productcustomization need in an economically and technically realizable manner. However,without customized treatment reaching the patient the benefit of personalized medicinescannot be achieved. Hence, a mass customization-paradigm, i.e. economic feasibilitywhen designing, producing and delivering customized pharmaceutical products, is desired.Pharmaceutical product customization has been discussed from a product and productionperspective. These discussions mainly focus either on product or production design.Additionally, the economic feasibility of suggested approaches is not fully explored.Mass customization requires joint consideration of product and production system design.Hence, the aim of this thesis is to explore integrated pharmaceutical product and productionsystem design facilitating a shift toward mass customization-paradigm.Methodologies to design the integrated product and production systems of pharmaceuticalproducts supporting customization are proposed. Set-based concurrent engineering(SBCE) principles are adapted due to the ability of efficient product development.Platform-based design is adapted due to a successful approach to mass customization inmanufacturing industry. Additionally, an integrated design approach to product value assessment is proposed to emphasize the customized pharmaceutical product value.The methodology application is illustrated for oral dosage forms for the purpose of demonstrating refined approaches to integrated design of these. Knowledge regarding oral dosage forms as enablers for personalized medicines is generated.Results show that the adaption of SBCE principles enables efficient consequence analysisof pharmaceutical product designs for production system designs and is accomplished byacquiring a set-based approach to simultaneous assessment of the performance of variousdesigns. Platform-based design enables flexible pharmaceutical product and productionsystem design, thus supporting mass customization. Finally, oral dosage forms embracingmodularized designs provide substantial product design flexibility but affects manufacturingcomplexity and hence, the discussion of product and production system design cannotbe separated

The State of the Art of Information Integration in Space Applications

This paper aims to present a comprehensive survey on information integration (II) in space informatics. With an ever-increasing scale and dynamics of complex space systems, II has become essential in dealing with the complexity, changes, dynamics, and uncertainties of space systems. The applications of space II (SII) require addressing some distinctive functional requirements (FRs) of heterogeneity, networking, communication, security, latency, and resilience; while limited works are available to examine recent advances of SII thoroughly. This survey helps to gain the understanding of the state of the art of SII in sense that (1) technical drivers for SII are discussed and classified; (2) existing works in space system development are analyzed in terms of their contributions to space economy, divisions, activities, and missions; (3) enabling space information technologies are explored at aspects of sensing, communication, networking, data analysis, and system integration; (4) the importance of first-time right (FTR) for implementation of a space system is emphasized, the limitations of digital twin (DT-I) as technological enablers are discussed, and a concept digital-triad (DT-II) is introduced as an information platform to overcome these limitations with a list of fundamental design principles; (5) the research challenges and opportunities are discussed to promote SII and advance space informatics in future

Multi-Input Multi-Output Target-Speaker Voice Activity Detection For Unified, Flexible, and Robust Audio-Visual Speaker Diarization

Audio-visual learning has demonstrated promising results in many classical speech tasks (e.g., speech separation, automatic speech recognition, wake-word spotting). We believe that introducing visual modality will also benefit speaker diarization. To date, Target-Speaker Voice Activity Detection (TS-VAD) plays an important role in highly accurate speaker diarization. However, previous TS-VAD models take audio features and utilize the speaker's acoustic footprint to distinguish his or her personal speech activities, which is easily affected by overlapped speech in multi-speaker scenarios. Although visual information naturally tolerates overlapped speech, it suffers from spatial occlusion, low resolution, etc. The potential modality-missing problem blocks TS-VAD towards an audio-visual approach. This paper proposes a novel Multi-Input Multi-Output Target-Speaker Voice Activity Detection (MIMO-TSVAD) framework for speaker diarization. The proposed method can take audio-visual input and leverage the speaker's acoustic footprint or lip track to flexibly conduct audio-based, video-based, and audio-visual speaker diarization in a unified sequence-to-sequence framework. Experimental results show that the MIMO-TSVAD framework demonstrates state-of-the-art performance on the VoxConverse, DIHARD-III, and MISP 2022 datasets under corresponding evaluation metrics, obtaining the Diarization Error Rates (DERs) of 4.18%, 10.10%, and 8.15%, respectively. In addition, it can perform robustly in heavy lip-missing scenarios.Comment: Under review of IEEE/ACM Transactions on Audio, Speech, and Language Processin

Wearable feedback systems for rehabilitation

In this paper we describe LiveNet, a flexible wearable platform intended for long-term ambulatory health monitoring with real-time data streaming and context classification. Based on the MIT Wearable Computing Group's distributed mobile system architecture, LiveNet is a stable, accessible system that combines inexpensive, commodity hardware; a flexible sensor/peripheral interconnection bus; and a powerful, light-weight distributed sensing, classification, and inter-process communications software architecture to facilitate the development of distributed real-time multi-modal and context-aware applications. LiveNet is able to continuously monitor a wide range of physiological signals together with the user's activity and context, to develop a personalized, data-rich health profile of a user over time. We demonstrate the power and functionality of this platform by describing a number of health monitoring applications using the LiveNet system in a variety of clinical studies that are underway. Initial evaluations of these pilot experiments demonstrate the potential of using the LiveNet system for real-world applications in rehabilitation medicine

Trends in virtual reality technologies for the learning patient

NextMed convened the Medicine Meets Virtual Reality 22 (MMVR 22) conference in 2016. Since 1992, the conference has brought together a diverse group of researchers to share creative solutions for the evolving challenge of integrating virtual reality tools into medical education. Virtual reality (VR) and its enabling technologies utilize hardware and software to simulate environments and encounters where users can interact and learn. The MMVR 22 symposium proceedings contain projects that support a variety of learners: medical students, practitioners, soldiers, and patients. This report will contemplate the trends in virtual reality technologies for patients navigating their medical and healthcare learning. The learning patient seeks more than intervention; they seek prevention. From virtual humans and environments to motion sensors and haptic devices, patients are surrounded by increasingly rich and transformative data-driven tools. Applied data enables VR applications to simulate experience, predict health outcomes, and motivate new behavior. The MMVR 22 presents investigations into the usability of wearable devices, the efficacy of avatar inclusion, and the viability of multi-player gaming. With increasing need for individualized and scalable programming, only committed open source efforts will align instructional designers, technology integrators, trainers, and clinicians. Curriculum and InstructionCurriculum and Instructio

The Knowledge Grid: A Platform to Increase the Interoperability of Computable Knowledge and Produce Advice for Health

Here we demonstrate how more highly interoperable computable knowledge enables systems to generate large quantities of evidence-based advice for health. We first provide a thorough analysis of advice. Then, because advice derives from knowledge, we turn our focus to computable, i.e., machine-interpretable, forms for knowledge. We consider how computable knowledge plays dual roles as a resource conveying content and as an advice enabler. In this latter role, computable knowledge is combined with data about a decision situation to generate advice targeted at the pending decision. We distinguish between two types of automated services. When a computer system provides computable knowledge, we say that it provides a knowledge service. When computer system combines computable knowledge with instance data to provide advice that is specific to an unmade decision we say that it provides an advice-giving service. The work here aims to increase the interoperability of computable knowledge to bring about better knowledge services and advice-giving services for health. The primary motivation for this research is the problem of missing or inadequate advice about health topics. The global demand for well-informed health advice far exceeds the global supply. In part to overcome this scarcity, the design and development of Learning Health Systems is being pursued at various levels of scale: local, regional, state, national, and international. Learning Health Systems fuse capabilities to generate new computable biomedical knowledge with other capabilities to rapidly and widely use computable biomedical knowledge to inform health practices and behaviors with advice. To support Learning Health Systems, we believe that knowledge services and advice-giving services have to be more highly interoperable. I use examples of knowledge services and advice-giving services which exclusively support medication use. This is because I am a pharmacist and pharmacy is the biomedical domain that I know. The examples here address the serious problems of medication adherence and prescribing safety. Two empirical studies are shared that demonstrate the potential to address these problems and make improvements by using advice. But primarily we use these examples to demonstrate general and critical differences between stand-alone, unique approaches to handling computable biomedical knowledge, which make it useful for one system, and common, more highly interoperable approaches, which can make it useful for many heterogeneous systems. Three aspects of computable knowledge interoperability are addressed: modularity, identity, and updateability. We demonstrate that instances of computable knowledge, and related instances of knowledge services and advice-giving services, can be modularized. We also demonstrate the utility of uniquely identifying modular instances of computable knowledge. Finally, we build on the computing concept of pipelining to demonstrate how computable knowledge modules can automatically be updated and rapidly deployed. Our work is supported by a fledgling technical knowledge infrastructure platform called the Knowledge Grid. It includes formally specified compound digital objects called Knowledge Objects, a conventional digital Library that serves as a Knowledge Object repository, and an Activator that provides an application programming interface (API) for computable knowledge. The Library component provides knowledge services. The Activator component provides both knowledge services and advice-giving services. In conclusion, by increasing the interoperability of computable biomedical knowledge using the Knowledge Grid, we demonstrate new capabilities to generate well-informed health advice at a scale. These new capabilities may ultimately support Learning Health Systems and boost health for large populations of people who would otherwise not receive well-informed health advice.PHDInformationUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/146073/1/ajflynn_1.pd

Innovation Of, In, On Infrastructures: Articulating the Role of Architecture in Information Infrastructure Evolution

In this paper, we address the question: “which conditions enable successful information infrastructure innovation?”. Information infrastructures are characterized by nonlinear evolutionary dynamics. Based on a case study that examines the design, development, and initial use of a web-based solution for patient-hospital communication at a Norwegian hospital over a ten-year period, we trace the evolution of a new II. This longitudinal analysis takes installed base cultivation as its conceptual basis. Specifically, we draw on three aspects of a cultivation strategy: growth process, user mobilization, and learning to cultivate. The analysis shows how the solution started as a bottom-up initiative of a small and motivated team at the hospital IT department, and how it grew gradually in a flexible and evolutionary way. Our findings support the argument that successful infrastructure innovations are based on a cultivation strategy addressing specific users’ needs, usefulness, and evolutionary growth. We make three key contributions to information infrastructure research. First, we expose the role architecture plays in the growth of IIs. Second, we provide insights about cultivating IIs, especially in their bootstrap phase. Third, we identify three different but interrelated types of innovation—in, of, on infrastructure—that articulate the critical role of IIs architecture in enabling successful innovation

Aggregation of Hospital Business Processes

There are estimates that up to 30% of hospital costs are due to inefficiently coordinated hospital processes. As a result many hospitals have tried to model and to reengineer their business processes. These efforts have very often been abandoned, because the normally constructed total models of hospital processes could hardly cope with the rapid technological and medical progress as well as with changing staff. We discuss approaches for a qualitative and quantitative process modularization which improve the understanding of processes and enables better planned simulations. Various methods are discussed which allow a qualitative modularization on the basis of a disaggregated process graph. To cope with this modularization numerically simple semi-stochastic formulas are developed for the calculation of expected values and variances of cycle times and costs from micro-data up to the modular level. Thus a qualitative as well as quantitative discussion of hospital business processes on the modular level become possible.OR in health care service, graph theory, business process reengineering, stochastic processes, simulation