Delivery Paradigm Research Articles

PMTCT Option B+: An opportunity for shaping a new service delivery paradigm

PMTCT Option B+: An opportunity for shaping a new service delivery paradigm

Chapter 7: Pharmacogenomics

There is great variation in drug-response phenotypes, and a “one size fits all” paradigm for drug delivery is flawed. Pharmacogenomics is the study of how human genetic information impacts drug response, and it aims to improve efficacy and reduced side effects. In this article, we provide an overview of pharmacogenetics, including pharmacokinetics (PK), pharmacodynamics (PD), gene and pathway interactions, and off-target effects. We describe methods for discovering genetic factors in drug response, including genome-wide association studies (GWAS), expression analysis, and other methods such as chemoinformatics and natural language processing (NLP). We cover the practical applications of pharmacogenomics both in the pharmaceutical industry and in a clinical setting. In drug discovery, pharmacogenomics can be used to aid lead identification, anticipate adverse events, and assist in drug repurposing efforts. Moreover, pharmacogenomic discoveries show promise as important elements of physician decision support. Finally, we consider the ethical, regulatory, and reimbursement challenges that remain for the clinical implementation of pharmacogenomics.

Intelligent Design of Multifunctional lipid-coated Nanoparticle Platforms for Cancer Therapy

Nanotechnology is rapidly evolving and dramatically changing the paradigms of drug delivery. The small sizes, unique chemical properties, large surface areas, structural diversity and multifunctionality of nanoparticles prove to be greatly advantageous for combating notoriously therapeutically evasive diseases such as cancer. Multifunctional nanoparticles have been designed to enhance tumor uptake through either passive or active targeting, while also avoiding reticuloendothelial system uptake through the incorporation of PEG onto the surface. First-generation nanoparticle systems, such as liposomes, are good carriers for drugs and nucleic acid therapeutics, although they have some limitations. These lipid bilayers are now being utilized as excellent carriers for drug-loaded, solid core particles such as iron oxide, mesoporus silica and calcium phosphate. In this article, their design, as well as their multifunctional role in cancer therapy are discussed.

Image-guided radiotherapy: from current concept to future perspectives

Radiotherapy is a highly effective, targeted therapy for the management of cancer. Technological innovations have enabled the direct integration of imaging technology into the radiation treatment device to increase the precision and accuracy of radiation delivery. As well as addressing a clinical need to better control the placement of the dose within the body, image-guided radiotherapy has enabled innovators in the field to accelerate their exploration of a number of different paradigms of radiation delivery, including toxicity reduction, dose escalation, hypofractionation, voxelization, and adaptation. Although these approaches are already innovative trends in radiation oncology, it is anticipated that they will work synergistically with other innovations in cancer management (including biomarker strategies, novel systemic and local therapies) as part of the broader goal of personalized cancer medicine. This Review discusses the rationale for adopting image-guidance approaches in radiotherapy, and the technology for achieving precision and accuracy in the context of different paradigms within the evolving radiation oncology practice. It also examines exciting advances in radiotherapy technology that suggest a convergence of radiotherapy practice in which patient-specific radiotherapy treatment courses are one of the most personalized forms of intervention in cancer medicine.

Serving Electricity and Heat Requirements Efficiently and with Appropriate Energy Quality via Microgrids

The familiar power delivery paradigm is in need of revision. The autonomously controlled assets of local systems, or microgrids, can provide multiple levels of power quality and reliability, customizing the power delivered to requirements. This in turn can free up the legacy grid to operate at a level of power quality and reliability better suited to our current societal goals.

Lack of Access in Healthcare Delivery: A Model for Using Dental Hygienists in a Cost Effective Manner to Help Address the Oral Healthcare Problem

The healthcare delivery of the United States is confronted with many issues and problems. In an attempt to deal with them, the country has been engaged in a process of healthcare reform. Unfortunately, this reform has largely focused on who is going to pay, what is going to be covered, and how all of the constituencies are hopefully going to be satisfied. What have been largely unaddressed are new delivery paradigms or how the care will be distributed to the underserved. The authors attempt to seek solutions to these last two areas of concern. They spell out how the expansion of the scope of practice for dental hygienists will allow them to bridge the gaps in service and to help deliver dental coverage and elements of systemic healthcare to underserved populations. Finally, the authors provide the steps and mechanisms of how the scope of practice can be expanded. Policy and educational requirements are considered.

Empowering citizens with access control mechanisms to their personal health resources

BackgroundAdvancements in information and communication technologies have allowed the development of new approaches to the management and use of healthcare resources. Nowadays it is possible to address complex issues such as meaningful access to distributed data or communication and understanding among heterogeneous systems. As a consequence, the discussion focuses on the administration of the whole set of resources providing knowledge about a single subject of care (SoC). New trends make the SoC administrator and responsible for all these elements (related to his/her demographic data, health, well-being, social conditions, etc.) and s/he is granted the ability of controlling access to them by third parties. The subject of care exchanges his/her passive role without any decision capacity for an active one allowing to control who accesses what. PurposeWe study the necessary access control infrastructure to support this approach and develop mechanisms based on semantic tools to assist the subject of care with the specification of access control policies. This infrastructure is a building block of a wider scenario, the Person-Oriented Virtual Organization (POVO), aiming at integrating all the resources related to each citizen's health-related data. The POVO covers the wide range and heterogeneity of available healthcare resources (e.g., information sources, monitoring devices, or software simulation tools) and grants each SoC the access control to them. MethodsSeveral methodological issues are crucial for the design of the targeted infrastructure. The distributed system concept and focus are reviewed from the service oriented architecture (SOA) perspective. The main frameworks for the formalization of distributed system architectures (Reference Model-Open Distributed Processing, RM-ODP; and Model Driven Architecture, MDA) are introduced, as well as how the use of the Unified Modelling Language (UML) is standardized. The specification of access control policies and decision making mechanisms are essential keys for this approach and they are accomplished by using semantic technologies (i.e., ontologies, rule languages, and inference engines). ResultsThe results are mainly focused on the security and access control of the proposed scenario. An ontology has been designed and developed for the POVO covering the terminology of the scenario and easing the automation of administration tasks. Over that ontology, an access control mechanism based on rule languages allows specifying access control policies, and an inference engine performs the decision making process automatically. The usability of solutions to ease administration tasks to the SoC is improved by the Me-As-An-Admin (M3A) application. This guides the SoC through the specification of personal access control policies to his/her distributed resources by using semantic technologies (e.g., metamodeling, model-to-text transformations, etc.). All results are developed as services and included in an architecture in accordance with standards and principles of openness and interoperability. ConclusionsCurrent technology can bring health, social and well-being care actually centered on citizens, and granting each person the management of his/her health information. However, the application of technology without adopting methodologies or normalized guidelines will reduce the interoperability of solutions developed, failing in the development of advanced services and improved scenarios for health delivery. Standards and reference architectures can be cornerstones for future-proof and powerful developments. Finally, not only technology must follow citizen-centric approaches, but also the gaps needing legislative efforts that support these new paradigms of healthcare delivery must be identified and addressed.

Palliative and End-of-Life Care for Patients With Ovarian Cancer

Palliative care improves the quality of life of patients and their families through the prevention and treatment of distressing symptoms while addressing the psychological, social, and spiritual aspects of patient care. Emerging paradigms of delivery promote early involvement in the disease trajectory and specialty approaches to care. Interdisciplinary assessment and shared decision making are important components. Throughout the disease course, aggressive symptom management can improve patients' quality of life and their ability to tolerate and continue treatment. End-of-life care focuses on comfort, control, meaning, and support that become particularly intense when death is imminent.

Service Program Mobility: A new Paradigm for Mobile Operators' Service Delivery

The delivery of emerging, high performance mobile services is traditionally limited to the cellular operator home domain. Due to the centralized nature of service platforms, resource-demanding services suffer from long delays when a user is accessing them when roaming. With the globalization of our society, such data intensive services are enabled at the high cost required by provisioning high-speed inter-domain connections. Delivering those services from the local, visited domain (instead of the home domain), does not only overcome the aforementioned limitations, but also opens new possibilities for service delivery. An operator could expand its service delivery reach to a global coverage, enjoying all the benefits of such a move. We propose Service Program Mobility as a novel paradigm for global service provisioning. Our system architecture realizes dynamic service component migration across operator domains and platforms to offer the same experience to roaming users as they would have in the home network.

Decreasing Disease Severity in Symptomatic,Smn−/−;SMN2+/+, Spinal Muscular Atrophy Mice Following scAAV9-SMN Delivery

Spinal muscular atrophy (SMA), an autosomal recessive neuromuscular disorder, is the leading genetic cause of infant mortality. SMA is caused by the homozygous loss of Survival Motor Neuron-1 (SMN1). In humans, a nearly identical copy gene is present, SMN2. SMN2 is retained in all SMA patients and encodes the same protein as SMN1. However, SMN1 and SMN2 differ by a silent C-to-T transition at the 5' end of exon 7, causing alternative splicing of SMN2 transcripts and low levels of full-length SMN. SMA is monogenic and therefore well suited for gene-replacement strategies. Recently, self-complementary adeno-associated virus (scAAV) vectors have been used to deliver the SMN cDNA to an animal model of disease, the SMNΔ7 mouse. In this study, we examine a severe model of SMA, Smn(-/-);SMN2(+/+), to determine whether gene replacement is viable in a model in which disease development begins in utero. Using two delivery paradigms, intracerebroventricular injections and intravenous injections, we delivered scAAV9-SMN and demonstrated a two to four fold increase in survival, in addition to improving many of the phenotypic parameters of the model. This represents the longest extension in survival for this severe model for any therapeutic intervention and suggests that postsymptomatic treatment of SMA may lead to significant improvement of disease severity.

Editorial

Cloud computing has emerged as a new paradigm for the on-demand delivery of computing services to consumers as utilities. Given its innovative nature compared to the standard model of service provisioning, cloud computing raises new questions in terms of security, privacy and trust. Therefore, our focus in this special issue is to analyse the security, privacy and trust aspects of cloud with the aim of providing trusted cloud systems. In this editorial, we first provide a brief overview on various aspects of security, privacy and trust in cloud systems and discuss related recent research and development activities. We then present a brief summary of each of the papers included in this special issue.

Telepsychiatry: A New Paradigm for Mental Health Care Delivery

Telepsychiatry: A New Paradigm for Mental Health Care Delivery

Nanoparticles - A paradigm for topical drug delivery

The Drug Development and Therapeutics (DDT) is an open access peer-reviewed journal committed to publishing high-quality articles in the field of Drug synthesis and development and Therapeutics from industry, Clinicians and Academia.

Treating Childhood Anxiety in Schools: Service Delivery in a Response to Intervention Paradigm

Millions of youth who attend schools in the United States suffer from clinically significant anxiety. Left untreated, these students often experience significant disruptions in their academic, social, and family functioning. Fortunately, promising treatments exist for childhood anxiety that are amenable for delivery in school settings. However, educational law and new service delivery paradigms such as response-to-intervention (RtI) affect the delivery of anxiety interventions. In light of extant laws and practices that govern education, this article discusses the provision of supportive services to address childhood anxiety. Specifically, this article reviews how RtI, the Individuals with Disabilities Education Improvement Act, and Section 504 of the Rehabilitation Act guide service delivery and subsequently impact school-based anxiety treatments. Suggestions are provided to address childhood anxiety within a framework that allows for graduated and fluid service delivery.

Transposon-Mediated Gene Transfer into Adult and Induced Pluripotent Stem Cells

Transposon technology is a particularly attractive non-viral gene delivery paradigm that allows for efficient genomic integration into a variety of different cell types. In particular, transposon-mediated gene transfer is a promising tool for stem cell research, by virtue of its ability to efficiently and stably transfer genes into adult and induced pluripotent stem (iPS) cells. Moreover, transposons open up new perspectives for non-viral-mediated stem cell-based gene therapy. Several transposon systems, especially the Sleeping Beauty (SB), the piggyBac (PB) and Tol2, have been optimized for gene transfer into mammalian cells. In particular, SB resulted in stable gene transfer into various adult stem cells including human CD34(+) hematopoietic stem cells (HSCs), myoblasts and mesenchymal stem cells (MSCs). This has been confirmed with PB, yielding stable gene transfer in human CD34(+) HSCs. Recently, PB transposons were used to deliver the genes encoding the reprogramming factors into somatic cells making it an attractive technology for generating iPS cells. Subsequent de novo expression of the PB transposase resulted in traceless excision of the reprogramming cassette. This prevented inadvertent re-expression of the reprogramming factors obviating some of the concerns associated with the use of integrating vectors. Transposons have also been used as a novel non-viral paradigm to coax differentiation of iPS cells into their desired target cells by forced expression of specific differentiation factors. This review focuses on the emerging potential of transposons for gene transfer into stem cells and its implications for gene therapy and regenerative medicine.

Towards intelligent contention-based geographic forwarding in wireless sensor networks

Contention-based geographic forwarding (CGF) is a state-free communication paradigm for data delivery in multihop wireless sensor networks. CGF is robust to frequent topology changes, scalable to large-scale node deployment and applicable to data-centric applications and resource constrained networks. However, CGF may experience significant performance degradation under unreliable links. In this work, we present the intelligent CGF (ICGF) to combat the channel variation. IGCF combines the advantages of both cooperative and contention-based forwarding, involving multiple neighbours of the sender into the local forwarding to improve the transmission reliability. ICGF differs from existing work in that it extends the cooperation scope intelligently, by sending one additional control message on demand. For this reason, the probability of cooperation void in ICGF is decreased and the single-hop packet progress is increased. The authors conduct extensive simulations to study the performance of the proposed ICGF compared with existing protocols. Simulation results demonstrate that ICGF improves the end-to-end data delivery delay, energy efficiency and data delivery ratio.

The gap junction life cycle

The gap junction life cycle

GDNF fails to exert neuroprotection in a rat -synuclein model of Parkinson's disease

The neuroprotective effect of the glial cell line-derived neurotrophic factor has been extensively studied in various toxic models of Parkinson's disease. However, it remains unclear whether this neurotrophic factor can protect against the toxicity induced by the aggregation-prone protein α-synuclein. Targeted overexpression of human wild-type α-synuclein in the nigrostriatal system, using adeno-associated viral vectors, causes a progressive degeneration of the nigral dopamine neurons and the development of axonal pathology in the striatum. In the present study, we investigated, using different paradigms of delivery, whether glial cell line-derived neurotrophic factor can protect against the neurodegenerative changes and the cellular stress induced by α-synuclein. We found that viral vector-mediated delivery of glial cell line-derived neurotrophic factor into substantia nigra and/or striatum, administered 2-3 weeks before α-synuclein, was inefficient in preventing the wild-type α-synuclein-induced loss of dopamine neurons and terminals. In addition, glial cell line-derived neurotrophic factor overexpression did not ameliorate the behavioural deficit in this rat model of Parkinson's disease. Quantification of striatal α-synuclein-positive aggregates revealed that glial cell line-derived neurotrophic factor had no effect on α-synuclein aggregation. These data provide the evidence for the lack of neuroprotective effect of glial cell line-derived neurotrophic factor against the toxicity of human wild-type α-synuclein in an in vivo model of Parkinson's disease. The difference in neuroprotective efficacy of glial cell line-derived neurotrophic factor seen in our model and the commonly used neurotoxin models of Parkinson's disease, raises important issues pertinent to the interpretation of the results obtained in preclinical models of Parkinson's disease, and their relevance for the therapeutic use glial cell line-derived neurotrophic factor in patients with Parkinson's disease.

Controlled epi-cortical delivery of epidermal growth factor for the stimulation of endogenous neural stem cell proliferation in stroke-injured brain

One of the challenges in treating central nervous system (CNS) disorders with biomolecules is achieving local delivery while minimizing invasiveness. For the treatment of stroke, stimulation of endogenous neural stem/progenitor cells (NSPCs) by growth factors is a promising strategy for tissue regeneration. Epidermal growth factor (EGF) enhances proliferation of endogenous NSPCs in the subventricular zone (SVZ) when delivered directly to the ventricles of the brain; however, this strategy is highly invasive. We designed a biomaterials-based strategy to deliver molecules directly to the brain without tissue damage. EGF or poly(ethylene glycol)-modified EGF (PEG-EGF) was dispersed in a hyaluronan and methylcellulose (HAMC) hydrogel and placed epi-cortically on both uninjured and stroke-injured mouse brains. PEG-modification decreased the rate of EGF degradation by proteases, leading to a significant increase in protein accumulation at greater tissue depths than previously shown. Consequently, EGF and PEG-EGF increased NSPC proliferation in uninjured and stroke-injured brains; and in stroke-injured brains, PEG-EGF significantly increased NSPC stimulation. Our epi-cortical delivery system is a minimally-invasive method for local delivery to the brain, providing a new paradigm for local delivery to the brain.

Diabetes Population Management by Telephone Visits

Little has been published on the impact of telephone visits on diabetes outcome performance. An attending and resident physician prioritized telephone visits based on glycemic, blood pressure, and lipid performance. The resident and attending panel was compared with all other diabetic patients at the clinic for baseline and end-intervention performance. The intervention patients had an absolute percentage of increase versus control patients of 14.9 (p<0.01), 13.9 (p<0.01), and 8.3 (p=0.01) for HbA1c <9%, low-density lipoprotein <100 mg/dL, and blood pressure <130/80 mm Hg, respectively. This pilot study suggests that provider-driven telephone visits may be a means for healthcare systems to improve chronic disease outcomes as they transition to new paradigms of chronic care delivery. This study was neither randomized nor blinded, was susceptible to an interventionist effect, and did not analyze for differences in baseline medication use.