Accounting for costs, QALYs, and capacity constraints: using discrete-event simulation to evaluate alternative service delivery and organizational scenarios for hospital-based glaucoma services.

PubMed

Crane, Glenis J; Kymes, Steven M; Hiller, Janet E; Casson, Robert; Martin, Adam; Karnon, Jonathan D

2013-11-01

Decision-analytic models are routinely used as a framework for cost-effectiveness analyses of health care services and technologies; however, these models mostly ignore resource constraints. In this study, we use a discrete-event simulation model to inform a cost-effectiveness analysis of alternative options for the organization and delivery of clinical services in the ophthalmology department of a public hospital. The model is novel, given that it represents both disease outcomes and resource constraints in a routine clinical setting. A 5-year discrete-event simulation model representing glaucoma patient services at the Royal Adelaide Hospital (RAH) was implemented and calibrated to patient-level data. The data were sourced from routinely collected waiting and appointment lists, patient record data, and the published literature. Patient-level costs and quality-adjusted life years were estimated for a range of alternative scenarios, including combinations of alternate follow-up times, booking cycles, and treatment pathways. The model shows that a) extending booking cycle length from 4 to 6 months, b) extending follow-up visit times by 2 to 3 months, and c) using laser in preference to medication are more cost-effective than current practice at the RAH eye clinic. The current simulation model provides a useful tool for informing improvements in the organization and delivery of glaucoma services at a local level (e.g., within a hospital), on the basis of expected effects on costs and health outcomes while accounting for current capacity constraints. Our model may be adapted to represent glaucoma services at other hospitals, whereas the general modeling approach could be applied to many other clinical service areas.

Intra-operatively customized implant coating strategies for local and controlled drug delivery to bone.

PubMed

Trajkovski, Branko; Petersen, Ansgar; Strube, Patrick; Mehta, Manav; Duda, Georg N

2012-09-01

Bone is one of the few tissues in the human body with high endogenous healing capacity. However, failure of the healing process presents a significant clinical challenge; it is a tremendous burden for the individual and has related health and economic consequences. To overcome such healing deficits, various concepts for a local drug delivery to bone have been developed during the last decades. However, in many cases these concepts do not meet the specific requirements of either surgeons who must use these strategies or individual patients who might benefit from them. We describe currently available methods for local drug delivery and their limitations in therapy. Various solutions for drug delivery to bone focusing on clinical applications and intra-operative constraints are discussed and drug delivery by implant coating is highlighted. Finally, a new set of design and performance requirements for intra-operatively customized implant coatings for controlled drug delivery is proposed. In the future, these requirements may improve approaches for local and intra-operative treatment of patients. Copyright © 2012 Elsevier B.V. All rights reserved.

Nitrogen fluxes at the root-soil interface show a mismatch of nitrogen fertilizer supply and sugarcane root uptake capacity

PubMed Central

Brackin, Richard; Näsholm, Torgny; Robinson, Nicole; Guillou, Stéphane; Vinall, Kerry; Lakshmanan, Prakash; Schmidt, Susanne; Inselsbacher, Erich

2015-01-01

Globally only ≈50% of applied nitrogen (N) fertilizer is captured by crops, and the remainder can cause pollution via runoff and gaseous emissions. Synchronizing soil N supply and crop demand will address this problem, however current soil analysis methods provide little insight into delivery and acquisition of N forms by roots. We used microdialysis, a novel technique for in situ quantification of soil nutrient fluxes, to measure N fluxes in sugarcane cropping soils receiving different fertilizer regimes, and compare these with N uptake capacities of sugarcane roots. We show that in fertilized sugarcane soils, fluxes of inorganic N exceed the uptake capacities of sugarcane roots by several orders of magnitude. Contrary, fluxes of organic N closely matched roots’ uptake capacity. These results indicate root uptake capacity constrains plant acquisition of inorganic N. This mismatch between soil N supply and root N uptake capacity is a likely key driver for low N efficiency in the studied crop system. Our results also suggest that (i) the relative contribution of inorganic N for plant nutrition may be overestimated when relying on soil extracts as indicators for root-available N, and (ii) organic N may contribute more to crop N supply than is currently assumed. PMID:26496834

Development of ocular drug delivery systems using molecularly imprinted soft contact lenses.

PubMed

Tashakori-Sabzevar, Faezeh; Mohajeri, Seyed Ahmad

2015-05-01

Recently, significant advances have been made in order to optimize drug delivery to ocular tissues. The main problems in ocular drug delivery are poor bioavailability and uncontrollable drug delivery of conventional ophthalmic preparations (e.g. eye drops). Hydrogels have been investigated since 1965 as new ocular drug delivery systems. Increase of hydrogel loading capacity, optimization of drug residence time on the ocular surface and biocompatibility with the eye tissue has been the main focus of previous studies. Molecular imprinting technology provided the opportunity to fulfill the above-mentioned objectives. Molecularly imprinted soft contact lenses (SCLs) have high potentials as novel drug delivery systems for the treatment of eye disorders. This technique is used for the preparation of polymers with specific binding sites for a template molecule. Previous studies indicated that molecular imprinting technology could be successfully applied for the preparation of SCLs as ocular drug delivery systems. Previous research, particularly in vivo studies, demonstrated that molecular imprinting is a versatile and effective method in optimizing the drug release behavior and enhancing the loading capacity of SCLs as new ocular drug delivery systems. This review highlights various potentials of molecularly imprinted contact lenses in enhancing the drug-loading capacity and controlling the drug release, compared to other ocular drug delivery systems. We have also studied the effects of contributing factors such as the type of comonomer, template/functional monomer molar ratio, crosslinker concentration in drug-loading capacity, and the release properties of molecularly imprinted hydrogels.

Muscle Tissue Engineering Using Gingival Mesenchymal Stem Cells Encapsulated in Alginate Hydrogels Containing Multiple Growth Factors.

PubMed

Ansari, Sahar; Chen, Chider; Xu, Xingtian; Annabi, Nasim; Zadeh, Homayoun H; Wu, Benjamin M; Khademhosseini, Ali; Shi, Songtao; Moshaverinia, Alireza

2016-06-01

Repair and regeneration of muscle tissue following traumatic injuries or muscle diseases often presents a challenging clinical situation. If a significant amount of tissue is lost the native regenerative potential of skeletal muscle will not be able to grow to fill the defect site completely. Dental-derived mesenchymal stem cells (MSCs) in combination with appropriate scaffold material, present an advantageous alternative therapeutic option for muscle tissue engineering in comparison to current treatment modalities available. To date, there has been no report on application of gingival mesenchymal stem cells (GMSCs) in three-dimensional scaffolds for muscle tissue engineering. The objectives of the current study were to develop an injectable 3D RGD-coupled alginate scaffold with multiple growth factor delivery capacity for encapsulating GMSCs, and to evaluate the capacity of encapsulated GMSCs to differentiate into myogenic tissue in vitro and in vivo where encapsulated GMSCs were transplanted subcutaneously into immunocompromised mice. The results demonstrate that after 4 weeks of differentiation in vitro, GMSCs as well as the positive control human bone marrow mesenchymal stem cells (hBMMSCs) exhibited muscle cell-like morphology with high levels of mRNA expression for gene markers related to muscle regeneration (MyoD, Myf5, and MyoG) via qPCR measurement. Our quantitative PCR analyzes revealed that the stiffness of the RGD-coupled alginate regulates the myogenic differentiation of encapsulated GMSCs. Histological and immunohistochemical/fluorescence staining for protein markers specific for myogenic tissue confirmed muscle regeneration in subcutaneous transplantation in our in vivo animal model. GMSCs showed significantly greater capacity for myogenic regeneration in comparison to hBMMSCs (p < 0.05). Altogether, our findings confirmed that GMSCs encapsulated in RGD-modified alginate hydrogel with multiple growth factor delivery capacity is a promising candidate for muscle tissue engineering.

BLOOD SUBSTITUTES: EVOLUTION FROM NON-CARRYING TO OXYGEN AND GAS CARRYING FLUIDS

PubMed Central

Cabrales, Pedro; Intaglietta, Marcos

2013-01-01

The development of oxygen (O2) carrying blood substitutes has evolved from the goal of replicating blood O2 transports properties to that of preserving microvascular and organ function, reducing the inherent or potential toxicity of the material used to carry O2, and treating pathologies initiated by anemia and hypoxia. Furthermore, the emphasis has shifted from blood replacement fluid to “O2 therapeutics” that restore tissue oxygenation to specific tissues regions. This review covers the different alternatives, potential and limitations of hemoglobin based O2 carriers (HBOCs) and perfluorocarbon based O2 carriers (PFCOCs), with emphasis on the physiological conditions disturbed in the situation that they will be used. It describes how concepts learned from plasma expanders without O2 carrying capacity can be applied to maintain O2 delivery and summarizes the microvascular responses due to HBOCs and PFCOCs. This review also presents alternative applications of HBOCs and PFCOCs namely: 1) How HBOC O2 affinity can be engineered to target O2 delivery to hypoxic tissues; and 2) How the high gas solubility of PFCOCs provides new opportunities for carrying, dissolving and delivering gases with biological activity. It is concluded that current blood substitutes development has amplified their applications horizon by devising therapeutic functions for oxygen carriers requiring limited O2 delivery capacity restoration. Conversely, full, blood-like O2 carrying capacity re-establishment awaits control of O2 carrier toxicity. PMID:23820271

Quantitative analysis of beam delivery parameters and treatment process time for proton beam therapy.

PubMed

Suzuki, Kazumichi; Gillin, Michael T; Sahoo, Narayan; Zhu, X Ronald; Lee, Andrew K; Lippy, Denise

2011-07-01

To evaluate patient census, equipment clinical availability, maximum daily treatment capacity, use factor for major beam delivery parameters, and treatment process time for actual treatments delivered by proton therapy systems. The authors have been recording all beam delivery parameters, including delivered dose, energy, range, spread-out Bragg peak widths, gantry angles, and couch angles for every treatment field in an electronic medical record system. We analyzed delivery system downtimes that had been recorded for every equipment failure and associated incidents. These data were used to evaluate the use factor of beam delivery parameters, the size of the patient census, and the equipment clinical availability of the facility. The duration of each treatment session from patient walk-in and to patient walk-out of the treatment room was measured for 82 patients with cancers at various sites. The yearly average equipment clinical availability in the last 3 yrs (June 2007-August 2010) was 97%, which exceeded the target of 95%. Approximately 2200 patients had been treated as of August 2010. The major disease sites were genitourinary (49%), thoracic (25%), central nervous system (22%), and gastrointestinal (2%). Beams have been delivered in approximately 8300 treatment fields. The use factor for six beam delivery parameters was also evaluated. Analysis of the treatment process times indicated that approximately 80% of this time was spent for patient and equipment setup. The other 20% was spent waiting for beam delivery and beam on. The total treatment process time can be expressed by a quadratic polynomial of the number of fields per session. The maximum daily treatment capacity of our facility using the current treatment processes was estimated to be 133 +/- 35 patients. This analysis shows that the facility has operated at a high performance level and has treated a large number of patients with a variety of diseases. The use factor of beam delivery parameters varies by disease site. Further improvements in efficiency may be realized in the equipment- and patient-related processes of treatment.

Supra-plasma expanders: the future of treating blood loss and anemia without red cell transfusions?

PubMed

Tsai, Amy G; Vázquez, Beatriz Y Salazar; Hofmann, Axel; Acharya, Seetharama A; Intaglietta, Marcos

2015-01-01

Oxygen delivery capacity during profoundly anemic conditions depends on blood's oxygen-carrying capacity and cardiac output. Oxygen-carrying blood substitutes and blood transfusion augment oxygen-carrying capacity, but both have given rise to safety concerns, and their efficacy remains unresolved. Anemia decreases oxygen-carrying capacity and blood viscosity. Present studies show that correcting the decrease of blood viscosity by increasing plasma viscosity with newly developed plasma expanders significantly improves tissue perfusion. These new plasma expanders promote tissue perfusion, increasing oxygen delivery capacity without increasing blood oxygen-carrying capacity, thus treating the effects of anemia while avoiding the transfusion of blood.

Leveraging socially networked mobile ICT platforms for the last-mile delivery problem.

PubMed

Suh, Kyo; Smith, Timothy; Linhoff, Michelle

2012-09-04

Increasing numbers of people are managing their social networks on mobile information and communication technology (ICT) platforms. This study materializes these social relationships by leveraging spatial and networked information for sharing excess capacity to reduce the environmental impacts associated with "last-mile" package delivery systems from online purchases, particularly in low population density settings. Alternative package pickup location systems (PLS), such as a kiosk on a public transit platform or in a grocery store, have been suggested as effective strategies for reducing package travel miles and greenhouse gas emissions, compared to current door-to-door delivery models (CDS). However, our results suggest that a pickup location delivery system operating in a suburban setting may actually increase travel miles and emissions. Only once a social network is employed to assist in package pickup (SPLS) are significant reductions in the last-mile delivery distance and carbon emissions observed across both urban and suburban settings. Implications for logistics management's decades-long focus on improving efficiencies of dedicated distribution systems through specialization, as well as for public policy targeting carbon emissions of the transport sector are discussed.

Chitosan based hydrogels: characteristics and pharmaceutical applications

PubMed Central

Ahmadi, F.; Oveisi, Z.; Samani, S. Mohammadi; Amoozgar, Z.

2015-01-01

Hydrogel scaffolds serve as semi synthetic or synthetic extra cellular matrix to provide an amenable environment for cellular adherence and cellular remodeling in three dimensional structures mimicking that of natural cellular environment. Additionally, hydrogels have the capacity to carry small molecule drugs and/or proteins, growth factors and other necessary components for cell growth and differentiation. In the context of drug delivery, hydrogels can be utilized to localize drugs, increase drugs concentration at the site of action and consequently reduce off-targeted side effects. The current review aims to describe and classify hydrogels and their methods of production. The main highlight is chitosan-based hydrogels as biocompatible and medically relevant hydrogels for drug delivery. PMID:26430453

Advances in hydrogel delivery systems for tissue regeneration.

PubMed

Toh, Wei Seong; Loh, Xian Jun

2014-12-01

Hydrogels are natural or synthetic polymer networks that have high water-absorbing capacity and closely mimic native extracellular matrices. As hydrogel-based cell delivery systems are being increasingly employed in regenerative medicine, several advances have been made in the hydrogel chemistry and modification for enhanced control of cell fate and functions, and modulation of cell and tissue responses against oxidative stress and inflammation in the tissue environment. This review aims to provide the state-of-the-art overview of the recent advances in field, discusses new perspectives and challenges in the regeneration of specific tissues, and highlights some of the limitations of current systems for possible future advancements. Copyright © 2014 Elsevier B.V. All rights reserved.

Information transmission on hybrid networks

NASA Astrophysics Data System (ADS)

Chen, Rongbin; Cui, Wei; Pu, Cunlai; Li, Jie; Ji, Bo; Gakis, Konstantinos; Pardalos, Panos M.

2018-01-01

Many real-world communication networks often have hybrid nature with both fixed nodes and moving modes, such as the mobile phone networks mainly composed of fixed base stations and mobile phones. In this paper, we discuss the information transmission process on the hybrid networks with both fixed and mobile nodes. The fixed nodes (base stations) are connected as a spatial lattice on the plane forming the information-carrying backbone, while the mobile nodes (users), which are the sources and destinations of information packets, connect to their current nearest fixed nodes respectively to deliver and receive information packets. We observe the phase transition of traffic load in the hybrid network when the packet generation rate goes from below and then above a critical value, which measures the network capacity of packets delivery. We obtain the optimal speed of moving nodes leading to the maximum network capacity. We further improve the network capacity by rewiring the fixed nodes and by considering the current load of fixed nodes during packets transmission. Our purpose is to optimize the network capacity of hybrid networks from the perspective of network science, and provide some insights for the construction of future communication infrastructures.

Microneedles for enhanced transdermal and intraocular drug delivery.

PubMed

Moffatt, Kurtis; Wang, Yujing; Raj Singh, Thakur Raghu; Donnelly, Ryan F

2017-10-01

Microneedle mediated delivery based research has garnered great interest in recent years. In the past, the initial focus was delivery of macromolecules of biological origin, however the field has now broadened its scope to include transdermal delivery of conventional low molecular weight drug molecules. Great success has been demonstrated utilising this approach, particularly in the field of vaccine delivery. Current technological advances have permitted an enhancement in design formulation, allowing delivery of therapeutic doses of small molecule drugs and biomolecules, aided by larger patch sizes and scalable manufacture. In addition, it has been recently shown that microneedles are beneficial in localisation of drug delivery systems within targeted ocular tissues. Microneedles have the capacity to modify the means in which therapeutics and formulations are delivered to the eye. However, further research is still required due to potential drawbacks and challenges. Indeed, no true microneedle-based transdermal or ocular drug delivery system has yet been marketed. Some concerns have been raised regarding regulatory issues and manufacturing processes of such systems, and those in the field are now actively working to address them. Microneedle-based transdermal and ocular drug delivery systems have the potential to greatly impact not only patient benefits, but also industry, and through diligence, innovation and collaboration, their true potential will begin to be realised within the next 3-5 years. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinically Relevant Physical Benefits of Exercise Interventions in Breast Cancer Survivors.

PubMed

Kirkham, Amy A; Bland, Kelcey A; Sayyari, Sarah; Campbell, Kristin L; Davis, Margot K

2016-02-01

Evidence is currently limited for the effect of exercise on breast cancer clinical outcomes. However, several of the reported physical benefits of exercise, including peak oxygen consumption, functional capacity, muscle strength and lean mass, cardiovascular risk factors, and bone health, have established associations with disability, cardiovascular disease risk, morbidity, and mortality. This review will summarize the clinically relevant physical benefits of exercise interventions in breast cancer survivors and discuss recommendations for achieving these benefits. It will also describe potential differences in intervention delivery that may impact outcomes and, lastly, describe current physical activity guidelines for cancer survivors.

Preparation, characterization and in vivo evaluation of a combination delivery system based on hyaluronic acid/jeffamine hydrogel loaded with PHBV/PLGA blend nanoparticles for prolonged delivery of Teriparatide.

PubMed

Bahari Javan, Nika; Montazeri, Hamed; Rezaie Shirmard, Leila; Jafary Omid, Nersi; Barbari, Ghullam Reza; Amini, Mohsen; Ghahremani, Mohammad Hossein; Rafiee-Tehrani, Morteza; Abedin Dorkoosh, Farid

2017-04-01

In the current study, biodegradable PHBV/PLGA blend nanoparticles (NPs) containing Teriparatide were loaded in hyaluronic acid/jeffamine (HA-JEF ED-600) hydrogel to prepare a combination delivery system (CDS) for prolonged delivery of Teriparatide. The principal purpose of the present study was to formulate an effective and prolonged Teriparatide delivery system in order to reduce the frequency of injection and thus enhance patient's compliance. Morphological properties, swelling behaviour, crosslinking efficiency and rheological characterization of HA-JEF ED-600 hydrogel were evaluated. The CDS was acquired by adding PHBV/PLGA NPs to HA-JEF ED-600 hydrogel simultaneously with crosslinking reaction. The percentage of NPs incorporation within the hydrogel as well as the loading capacity and morphology of Teriparatide loaded CDS were examined. Intrinsic fluorescence and circular dichroism spectroscopy proved that Teriparatide remains stable after processing. The release profile represented 63% Teriparatide release from CDS within 50days with lower burst release compared to NPs and hydrogel. MTT assay was conducted by using NIH3T3 cell line and no sign of reduction in cell viability was observed. Based on Miller and Tainter method, LD 50 of Teriparatide loaded CDS was 131.8mg/kg. In vivo studies demonstrated that Teriparatide loaded CDS could effectively increase serum calcium level after subcutaneous injection in mice. Favourable results in the current study introduced CDS as a promising candidate for controlled delivery of Teriparatide and pave the way for future investigations in the field of designing prolonged delivery systems for other peptides and proteins. Copyright © 2017 Elsevier B.V. All rights reserved.

Enhancement in ex vivo phagocytic capacity of peritoneal leukocytes in mice by oral delivery of various lactic-acid-producing bacteria.

PubMed

Lee, Yeonhee; Lee, Taik-Soo

2005-01-01

Lactic-acid-producing bacteria (LABs) are known to have immunomodulating activity. In the current study, various LABs were tested for their immunity-enhancing activity, especially the phagocytic activity of leukocytes. Viable but not heat-killed cells of Weissella kimchii strain PL9001, Lactobacillus fermentum strain PL9005, and L. plantarum strain PL9011 significantly increased the ex vivo phagocytic capacity of mouse peritoneal leukocytes to ingest fluorescein isothiocyanate (FITC)-labeled Escherichia coli in a strain-dependent manner. Results of this and previous studies suggest these LABs as candidates for new probiotics. This is the first report of the enhancement of peritoneal leukocyte activity of these species.

Quantitative analysis of treatment process time and throughput capacity for spot scanning proton therapy.

PubMed

Suzuki, Kazumichi; Palmer, Matthew B; Sahoo, Narayan; Zhang, Xiaodong; Poenisch, Falk; Mackin, Dennis S; Liu, Amy Y; Wu, Richard; Zhu, X Ronald; Frank, Steven J; Gillin, Michael T; Lee, Andrew K

2016-07-01

To determine the patient throughput and the overall efficiency of the spot scanning system by analyzing treatment time, equipment availability, and maximum daily capacity for the current spot scanning port at Proton Therapy Center Houston and to assess the daily throughput capacity for a hypothetical spot scanning proton therapy center. At their proton therapy center, the authors have been recording in an electronic medical record system all treatment data, including disease site, number of fields, number of fractions, delivered dose, energy, range, number of spots, and number of layers for every treatment field. The authors analyzed delivery system downtimes that had been recorded for every equipment failure and associated incidents. These data were used to evaluate the patient census, patient distribution as a function of the number of fields and total target volume, and equipment clinical availability. The duration of each treatment session from patient walk-in to patient walk-out of the spot scanning treatment room was measured for 64 patients with head and neck, central nervous system, thoracic, and genitourinary cancers. The authors retrieved data for total target volume and the numbers of layers and spots for all fields from treatment plans for a total of 271 patients (including the above 64 patients). A sensitivity analysis of daily throughput capacity was performed by varying seven parameters in a throughput capacity model. The mean monthly equipment clinical availability for the spot scanning port in April 2012-March 2015 was 98.5%. Approximately 1500 patients had received spot scanning proton therapy as of March 2015. The major disease sites treated in September 2012-August 2014 were the genitourinary system (34%), head and neck (30%), central nervous system (21%), and thorax (14%), with other sites accounting for the remaining 1%. Spot scanning beam delivery time increased with total target volume and accounted for approximately 30%-40% of total treatment time for the total target volumes exceeding 200 cm(3), which was the case for more than 80% of the patients in this study. When total treatment time was modeled as a function of the number of fields and total target volume, the model overestimated total treatment time by 12% on average, with a standard deviation of 32%. A sensitivity analysis of throughput capacity for a hypothetical four-room spot scanning proton therapy center identified several priority items for improvements in throughput capacity, including operation time, beam delivery time, and patient immobilization and setup time. The spot scanning port at our proton therapy center has operated at a high performance level and has been used to treat a large number of complex cases. Further improvements in efficiency may be feasible in the areas of facility operation, beam delivery, patient immobilization and setup, and optimization of treatment scheduling.

Television-Centered, Instructional Delivery Systems: Costs and Case Studies. A Review of Research.

ERIC Educational Resources Information Center

Maher, Thomas G.

This paper reviews the post-1975 research on the capacities, logistics, and costs of the various delivery technologies used in educational television, and details case studies of television-centered operations, particularly in relationship to adult learners. The paper begins with a section on general definitions and the capacities of various…

[Training and challenges for the health care system in Brazil: an analysis of investments to expand health care service delivery].

PubMed

Soares, Adilson

2007-07-01

The goal of this study is to discuss the investments made by the Brazilian government to expand health care service delivery in the Unified National Health System (SUS) from 1995 to 2001. The data indicate a mismatch between investments to increase service delivery and maintenance and optimization of the health service network's capacity. The paper concludes that there is a need to guarantee financial maintenance of the system and conduct new investments based on an analysis of the installed capacity and the financial possibilities to guarantee resources for continuous delivery of this additional services supply.

Transforming health care delivery through consumer engagement, health data transparency, and patient-generated health information.

PubMed

Sands, D Z; Wald, J S

2014-08-15

Address current topics in consumer health informatics. Literature review. Current health care delivery systems need to be more effective in the management of chronic conditions as the population turns older and experiences escalating chronic illness that threatens to consume more health care resources than countries can afford. Most health care systems are positioned poorly to accommodate this. Meanwhile, the availability of ever more powerful and cheaper information and communication technology, both for professionals and consumers, has raised the capacity to gather and process information, communicate more effectively, and monitor the quality of care processes. Adapting health care systems to serve current and future needs requires new streams of data to enable better self-management, improve shared decision making, and provide more virtual care. Changes in reimbursement for health care services, increased adoption of relevant technologies, patient engagement, and calls for data transparency raise the importance of patient-generated health information, remote monitoring, non-visit based care, and other innovative care approaches that foster more frequent contact with patients and better management of chronic conditions.

Status and future directions in the management of pancreatic cancer: potential impact of nanotechnology.

PubMed

Sielaff, Catherine M; Mousa, Shaker A

2018-07-01

Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at a late stage, has limited treatments, and patients have poor survival rates. It currently ranks as the seventh leading cause of cancer deaths globally and has increasing rates of diagnosis. Improved PDAC treatment requires the development of innovative, effective, and economical therapeutic drugs. The late stage diagnosis limits options for surgical resection, and traditional PDAC chemotherapeutics correlate with increased organ and hematologic toxicity. In addition, PDAC tumor tissue is dense and highly resistant to many traditional chemotherapeutic applications, making the disease difficult to treat and impeding options for palliative care. New developments in nanotechnology may offer innovative options for targeted PDAC therapeutic drug delivery. Nanotechnology can be implemented using multimodality methods that offer increased opportunities for earlier diagnosis, precision enhanced imaging, targeted long-term tumor surveillance, and controlled drug delivery, as well as improved palliative care and patient comfort. Nanoscale delivery methods have demonstrated the capacity to infiltrate the dense, fibrous tumor tissue associated with PDAC, increasing delivery and effectiveness of chemotherapeutic agents and reducing toxicity through the loading of multiple drug therapies on a single nano delivery vehicle. This review presents an overview of nanoscale drug delivery systems and multimodality carriers at the forefront of new PDAC treatments.

Toward an evidence-based system for innovation support for implementing innovations with quality: tools, training, technical assistance, and quality assurance/quality improvement.

PubMed

Wandersman, Abraham; Chien, Victoria H; Katz, Jason

2012-12-01

An individual or organization that sets out to implement an innovation (e.g., a new technology, program, or policy) generally requires support. In the Interactive Systems Framework for Dissemination and Implementation, a Support System should work with Delivery Systems (national, state and/or local entities such as health and human service organizations, community-based organizations, schools) to enhance their capacity for quality implementation of innovations. The literature on the Support System [corrected] has been underresearched and under-developedThis article begins to conceptualize theory, research, and action for an evidence-based system for innovation support (EBSIS). EBSIS describes key priorities for strengthening the science and practice of support. The major goal of EBSIS is to enhance the research and practice of support in order to build capacity in the Delivery System for implementing innovations with quality, and thereby, help the Delivery System achieve outcomes. EBSIS is guided by a logic model that includes four key support components: tools, training, technical assistance, and quality assurance/quality improvement. EBSIS uses the Getting To Outcomes approach to accountability to aid the identification and synthesis of concepts, tools, and evidence for support. We conclude with some discussion of the current status of EBSIS and possible next steps, including the development of collaborative researcher-practitioner-funder-consumer partnerships to accelerate accumulation of knowledge on the Support System.

Assessing the elimination of user fees for delivery services in Laos.

PubMed

Boudreaux, Chantelle; Chanthala, Phetdara; Lindelow, Magnus

2014-01-01

A pilot eliminating user fees associated with delivery at the point of services was introduced in two districts of Laos in March 2009. Following two years of implementation, an evaluation was conducted to assess the pilot impact, as well as to document the pilot design and implementation challenges. Study results show that, even in the presence of the substantial access and cultural barriers, user fees associated with delivery at health facilities act as a serious deterrent to care seeking behavior. We find a tripling of facility-based delivery rates in the intervention areas, compared to a 40% increase in the control areas. While findings from the control region suggest that facility-based delivery rates may be on the rise across the country, the substantially higher increase in the pilot areas highlight the impact of financial burden associated with facility-based delivery fees. These fees can play an important role in rapidly increasing the uptake of facility delivery to reach the national targets and, ultimately, to improve maternal and child health outcomes. The pilot achieved important gains while relying heavily on capacity and systems already in place. However, the high cost associated with monitoring and evaluation suggest broad-scale expansion of the pilot activities is likely to necessitate targeted capacity building initiatives, especially in areas with limited district level capacity to manage funds and deliver detailed and timely reports.

A Review of the Structure, Preparation, and Application of NLCs, PNPs, and PLNs.

PubMed

Li, Qianwen; Cai, Tiange; Huang, Yinghong; Xia, Xi; Cole, Susan P C; Cai, Yu

2017-05-27

Nanostructured lipid carriers (NLCs) are modified solid lipid nanoparticles (SLNs) that retain the characteristics of the SLN, improve drug stability and loading capacity, and prevent drug leakage. Polymer nanoparticles (PNPs) are an important component of drug delivery. These nanoparticles can effectively direct drug delivery to specific targets and improve drug stability and controlled drug release. Lipid-polymer nanoparticles (PLNs), a new type of carrier that combines liposomes and polymers, have been employed in recent years. These nanoparticles possess the complementary advantages of PNPs and liposomes. A PLN is composed of a core-shell structure; the polymer core provides a stable structure, and the phospholipid shell offers good biocompatibility. As such, the two components increase the drug encapsulation efficiency rate, facilitate surface modification, and prevent leakage of water-soluble drugs. Hence, we have reviewed the current state of development for the NLCs', PNPs', and PLNs' structures, preparation, and applications over the past five years, to provide the basis for further study on a controlled release drug delivery system.

A Review of the Structure, Preparation, and Application of NLCs, PNPs, and PLNs

PubMed Central

Li, Qianwen; Cai, Tiange; Huang, Yinghong; Xia, Xi; Cole, Susan P. C.; Cai, Yu

2017-01-01

Nanostructured lipid carriers (NLCs) are modified solid lipid nanoparticles (SLNs) that retain the characteristics of the SLN, improve drug stability and loading capacity, and prevent drug leakage. Polymer nanoparticles (PNPs) are an important component of drug delivery. These nanoparticles can effectively direct drug delivery to specific targets and improve drug stability and controlled drug release. Lipid–polymer nanoparticles (PLNs), a new type of carrier that combines liposomes and polymers, have been employed in recent years. These nanoparticles possess the complementary advantages of PNPs and liposomes. A PLN is composed of a core–shell structure; the polymer core provides a stable structure, and the phospholipid shell offers good biocompatibility. As such, the two components increase the drug encapsulation efficiency rate, facilitate surface modification, and prevent leakage of water-soluble drugs. Hence, we have reviewed the current state of development for the NLCs’, PNPs’, and PLNs’ structures, preparation, and applications over the past five years, to provide the basis for further study on a controlled release drug delivery system. PMID:28554993

Chemical Structure and Surface Modification of Dendritic Nanomaterials Tailored for Therapeutic and Diagnostic Applications.

PubMed

Myung, Ja Hye; Hsu, Hao-Jui; Bugno, Jason; Tam, Kevin A; Hong, Seungpyo

2017-01-01

Dendritic nanomaterials have attracted a great deal of scientific interest due to their high capacity for multifunctionalization and potential in various biomedical applications, such as drug/gene delivery and diagnostic systems. Depending on the molecular structure and starting monomers, several different types of dendrimers have been developed, including poly(amidoamine) (PAMAM), poly(propylenimine) (PPI), and poly(L-lysine) (PLL) dendrimers, in addition to modified dendritic nanomaterials, such as Janus dendrimers and dendritic block copolymers. The chemical structure and surface modification of dendritic nanomaterials have been found to play a critical role in governing their biological behaviors. In this review, we present a comprehensive overview focusing on the synthesis and chemical structures of dendrimers and modified dendritic nanomaterials that are currently being investigated for drug delivery, gene delivery, and diagnostic applications. In addition, the impact of chemical surface modification and functionalization to the dendritic nanomaterials on their therapeutic and diagnostic applications are highlighted. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Charge Injection Capacity of TiN Electrodes for an Extended Voltage Range

PubMed Central

Patan, Mustafa; Shah, Tosha; Sahin, Mesut

2011-01-01

Many applications of neural stimulation demand a high current density from the electrodes used for stimulus delivery. New materials have been searched that can provide such large current and charge densities where the traditional noble metal and capacitor electrodes are inadequate. Titanium nitride, which has been used in cardiac pacemaker leads for many years, is one of these materials recently considered for neural stimulation. In this short report, we investigated the charge injection capacity of TiN electrodes for an extended range of cathodic voltages. The injected charge increased first slowly as a function of the electrode voltage, and then at a faster rate beyond −1.6 V. The maximum charge was 4.45 mC/cm2 (n=6) for a cathodic voltage peak of −3.0 V and a bias voltage of −0.8 V. There was no evidence of bubble generation under microscopic observation. The unrecoverable charges remained under 7% of the total injected charge for the largest cathodic voltage tested. These large values of charge injection capacity and relatively small unrecoverable charges warrant further investigation of the charge injection mechanism in TiN interfaces at this extended range of electrode voltages. PMID:17946870

Harnessing the capacity of cell-penetrating peptides for drug delivery to the central nervous system.

PubMed

Kang, Ting; Gao, Xiaoling; Chen, Jun

2014-01-01

The existence of blood-brain barrier (BBB) represents the most formidable challenge for drug delivery to the central nervous system (CNS). Modern breakthrough in biology offers multiple choices for overcoming this barrier but yields modest outcomes for clinical application due to various problems such as safety concerns, insufficient delivery efficiency and poor penetration. Cell penetrating peptides (CPPs) possessing powerful transmembrane capacity have been shown to be effective transport vectors for bioactive molecules and an attractive alternative to traditional active targeting approaches. However, the non-specificity of CPPs has hindered them from targeting a desired site of action. Promisingly, design of novel CPP-mediated nanoparticulate delivery systems with specific targeting property may extricate CPPs from the dilemma. In this review, both the traditional and novel applications of CPPs-based strategies for CNS drug delivery will be discussed.

Quantitative analysis of treatment process time and throughput capacity for spot scanning proton therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suzuki, Kazumichi, E-mail: kazumichisuzuki@gmail.c

Purpose: To determine the patient throughput and the overall efficiency of the spot scanning system by analyzing treatment time, equipment availability, and maximum daily capacity for the current spot scanning port at Proton Therapy Center Houston and to assess the daily throughput capacity for a hypothetical spot scanning proton therapy center. Methods: At their proton therapy center, the authors have been recording in an electronic medical record system all treatment data, including disease site, number of fields, number of fractions, delivered dose, energy, range, number of spots, and number of layers for every treatment field. The authors analyzed delivery systemmore » downtimes that had been recorded for every equipment failure and associated incidents. These data were used to evaluate the patient census, patient distribution as a function of the number of fields and total target volume, and equipment clinical availability. The duration of each treatment session from patient walk-in to patient walk-out of the spot scanning treatment room was measured for 64 patients with head and neck, central nervous system, thoracic, and genitourinary cancers. The authors retrieved data for total target volume and the numbers of layers and spots for all fields from treatment plans for a total of 271 patients (including the above 64 patients). A sensitivity analysis of daily throughput capacity was performed by varying seven parameters in a throughput capacity model. Results: The mean monthly equipment clinical availability for the spot scanning port in April 2012–March 2015 was 98.5%. Approximately 1500 patients had received spot scanning proton therapy as of March 2015. The major disease sites treated in September 2012–August 2014 were the genitourinary system (34%), head and neck (30%), central nervous system (21%), and thorax (14%), with other sites accounting for the remaining 1%. Spot scanning beam delivery time increased with total target volume and accounted for approximately 30%–40% of total treatment time for the total target volumes exceeding 200 cm{sup 3}, which was the case for more than 80% of the patients in this study. When total treatment time was modeled as a function of the number of fields and total target volume, the model overestimated total treatment time by 12% on average, with a standard deviation of 32%. A sensitivity analysis of throughput capacity for a hypothetical four-room spot scanning proton therapy center identified several priority items for improvements in throughput capacity, including operation time, beam delivery time, and patient immobilization and setup time. Conclusions: The spot scanning port at our proton therapy center has operated at a high performance level and has been used to treat a large number of complex cases. Further improvements in efficiency may be feasible in the areas of facility operation, beam delivery, patient immobilization and setup, and optimization of treatment scheduling.« less

Association of intervention outcomes with practice capacity for change: Subgroup analysis from a group randomized trial

PubMed Central

Litaker, David; Ruhe, Mary; Weyer, Sharon; Stange, Kurt C

2008-01-01

Background The relationship between health care practices' capacity for change and the results and sustainability of interventions to improve health care delivery is unclear. Methods In the setting of an intervention to increase preventive service delivery (PSD), we assessed practice capacity for change by rating motivation to change and instrumental ability to change on a one to four scale. After combining these ratings into a single score, random effects models tested its association with change in PSD rates from baseline to immediately after intervention completion and 12 months later. Results Our measure of practices' capacity for change varied widely at baseline (range 2–8; mean 4.8 ± 1.6). Practices with greater capacity for change delivered preventive services to eligible patients at higher rates after completion of the intervention (2.7% per unit increase in the combined effort score, p < 0.001). This relationship persisted for 12 months after the intervention ended (3.1%, p < 0.001). Conclusion Greater capacity for change is associated with a higher probability that a practice will attain and sustain desired outcomes. Future work to refine measures of this practice characteristic may be useful in planning and implementing interventions that result in sustained, evidence-based improvements in health care delivery. PMID:18485216

Rapid and efficient nonviral gene delivery of CD154 to primary chronic lymphocytic leukemia cells.

PubMed

Li, L H; Biagi, E; Allen, C; Shivakumar, R; Weiss, J M; Feller, S; Yvon, E; Fratantoni, J C; Liu, L N

2006-02-01

Interactions between CD40 and CD40 ligand (CD154) are essential in the regulation of both humoral and cellular immune responses. Forced expression of human CD154 in B chronic lymphocytic leukemia (B-CLL) cells can upregulate costimulatory and adhesion molecules and restore antigen-presenting capacity. Unfortunately, B-CLL cells are resistant to direct gene manipulation with most currently available gene transfer systems. In this report, we describe the use of a nonviral, clinical-grade, electroporation-based gene delivery system and a standard plasmid carrying CD154 cDNA, which achieved efficient (64+/-15%) and rapid (within 3 h) transfection of primary B-CLL cells. Consistent results were obtained from multiple human donors. Transfection of CD154 was functional in that it led to upregulated expression of CD80, CD86, ICAM-I and MHC class II (HLA-DR) on the B-CLL cells and induction of allogeneic immune responses in MLR assays. Furthermore, sustained transgene expression was demonstrated in long-term cryopreserved transfected cells. This simple and rapid gene delivery technology has been validated under the current Good Manufacturing Practice conditions, and multiple doses of CD154-expressing cells were prepared for CLL patients from one DNA transfection. Vaccination strategies using autologous tumor cells manipulated ex vivo for patients with B-CLL and perhaps with other hematopoietic malignancies could be practically implemented using this rapid and efficient nonviral gene delivery system.

In-vitro photo-translocation of antiretroviral drug delivery into TZMbl cells

NASA Astrophysics Data System (ADS)

Malabi, Rudzani; Manoto, Sello; Ombinda-Lemboumba, Saturnin; Maaza, Malik; Mthunzi-Kufa, Patience

2017-02-01

The current human immunodeficiency virus (HIV) treatment regime possesses the ability to diminish the viral capacity to unnoticeable levels; however complete eradication of the virus cannot be achieved while latent HIV-1 reservoirs go unchallenged. Therapeutic targeting of HIV therefore requires further investigation and current therapies need modification in order to address HIV eradication. This deflects research towards investigating potential novel antiretroviral drug delivery systems. The use of femtosecond (fs) laser pulses in promoting targeted optical drug delivery of antiretroviral drugs (ARVs) into TZMbl cells revolves around using ultrafast laser pulses that have high peak powers, which precisely disrupt the cell plasma membrane in order to allow immediate transportation and expression of exogenous material into the live mammalian cells. A photo-translocation optical setup was built and validated by characterisation of the accurate parameters such as wavelength (800 nm) and pulse duration (115 fs). Optimisation of drug translocation parameters were done by performing trypan blue translocation studies. Cellular responses were determined via cell viability (Adenosine Triphosphate activity) and cell cytotoxicity (Lactate Dehydrogenase) assays which were done to study the influence of the drugs and laser exposure on the cells. After laser irradiation, high cell viability was observed and low toxicity levels were observed after exposure of the cells to both the ARVs and the laser. Our results confirmed that, with minimal damage and high therapeutic levels of ARVs, the fs laser assisted drug delivery system is efficient with benefits of non-invasive and non-toxic treatment to the cells.

Transgene Delivery using Poly(amino ether)-Gold Nanorod Assemblies

PubMed Central

Ramos, James; Rege, Kaushal

2012-01-01

Gold nanorods (GNRs) have emerged as promising nanomaterials for biosensing, imaging, photothermal treatment and therapeutic delivery for several diseases, including cancer. We have generated poly(amino ether)-functionalized gold nanorods (PAE-GNRs) using a layer-by-layer deposition approach; polymers from a poly(amino ether) library recently synthesized in our laboratory were employed to generate the PAE-GNR assemblies. PAE-GNR assemblies demonstrate long-term colloidal stability as well as the capacity to bind plasmid DNA by means of electrostatic interactions. Sub-toxic concentrations of PAE-GNRs were employed to deliver plasmid DNA to prostate cancer cells in vitro. PAE-GNRs generated using 1,4C-1,4Bis, a cationic polymer from our laboratory demonstrated significantly higher transgene expression and exhibited lower cytotoxicities when compared to similar assemblies generated using 25 kDa poly(ethylene imine) (PEI25k-GNRs), a current standard for polymer-mediated gene delivery. The roles of polyelectrolyte chemistry and zeta-potential in determining transgene expression efficacies of PAE-GNR assemblies were investigated. Our results indicate that stable and effective PAE-GNR assemblies are a promising engineered platform for transgene delivery. PAE-GNRs also have the potential to be used simultaneously for photothermal ablation, photothermally enhanced drug and gene delivery, and biological imaging, thus making them a powerful theranostic platform. PMID:22170455

Antioxidant Nanoplatforms for Dermal Delivery: Melatonin.

PubMed

Milan, Aroha Sanchez; Campmany, Ana Cristina Calpena; Naveros, Beatriz Clares

2017-01-01

Melatonin is emerging as a promising therapeutic agent, mainly due to its role as antioxidant. Substantial evidences show that melatonin is potentially effective in a variety of diseases as cancer, inflammation and neurodegenerative diseases. The excellent antioxidant capacity with pharmacokinetics characteristics and the emerging search for new pharmaceutical nanotechnology based systems, make it particularly attractive to elaborate nanoplatforms based on melatonin for biomedical or cosmetic dermal applications. Different nanosystems for dermal delivery have been investigated. This review focuses on nanocarrier production strategies, dermal melatonin application and delivery advances in vivo and in vitro. Equally, future perspectives of this assisted melatonin delivery have also been discussed. In the current review, we have revised relevant articles of the available literature using the major scientific databases. One hundred and thirteen papers were included in the review, the majority of which represent latest researches in nanosized platforms for the dermal delivery of melatonin including liposomes, ethosomes, niosomes, polymeric nanoparticles, solid lipid nanoparticles and cyclodextrins. Furthermore, relevant papers reporting in vitro and in vivo application studies of these nano-based melatonin platforms were also discussed. The use of nanoplatforms for the dermal melatonin delivery as antioxidant agent could improve the efficacy of conventional melatonin administration due to the preservation of the drug from premature oxidation and the enhancement of drug permeation through the skin providing greater exposure times. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

AIRTV: Broadband Direct to Aircraft

NASA Astrophysics Data System (ADS)

Sorbello, R.; Stone, R.; Bennett, S. B.; Bertenyi, E.

2002-01-01

Airlines have been continuously upgrading their wide-body, long-haul aircraft with IFE (in-flight entertainment) systems that can support from 12 to 24 channels of video entertainment as well as provide the infrastructure to enable in-seat delivery of email and internet services. This is a direct consequence of increased passenger demands for improved in-flight services along with the expectations that broadband delivery systems capable of providing live entertainment (news, sports, financial information, etc.) and high speed data delivery will soon be available. The recent events of Sept. 11 have slowed the airline's upgrade of their IFE systems, but have also highlighted the compelling need for broadband aeronautical delivery systems to include operational and safety information. Despite the impact of these events, it is estimated that by 2005 more than 3000 long haul aircraft (servicing approximately 1 billion passengers annually) will be fully equipped with modern IFE systems. Current aircraft data delivery systems, which use either Inmarsat or NATS, are lacking in bandwidth and consequently are unsuitable to satisfy passenger demands for broadband email/internet services or the airlines' burgeoning data requirements. Present live video delivery services are limited to regional coverage and are not readily expandable to global or multiregional service. Faced with a compelling market demand for high data transport to aircraft, AirTV has been developing a broadband delivery system that will meet both passengers' and airlines' needs. AirTV is a global content delivery system designed to provide a range of video programming and data services to commercial airlines. When AirTV is operational in 2004, it will provide a broadband connection directly to the aircraft, delivering live video entertainment, internet/email service and essential operational and safety data. The system has been designed to provide seamless global service to all airline routes except for those over the poles. The system consists of a constellation of 4 geostationary satellites covering the earth and delivering its signals to the aircraft at S band (2.52 -2.67 GHz). The S-band spectrum is ideal for this application since it is allocated on a primary basis by the ITU for global broadcast service. The AirTV service is expected to begin in 2004 and should be unencumbered by adjacent satellite interference due to near completion of the ITU coordination process. Each satellite will deliver four 20 Mbps QPSK data streams consisting of multiplexed compressed digital video channels and IP data over the full global beam coverage. The 80 Mbps capacity of each satellite will provide approximately 60 video channels while still allocating 40 Mbits to data services. The combined constellation capacity of 320 Mbits will significantly exceed the capacity of any similar existing or currently planned global satellite system. In addition, the simplicity of the 4-satellite approach is the most cost effective means to deliver high bandwidth globally. Return links, which are required for internet service, will be provided through the existing Inmarsat Aero-H system already onboard virtually all long haul aircraft and will provide return data rates from the aircraft as high as 432 kbps. integrated receiver/decoder (IRD) assembly. The phased array antenna, a key technology element, is being developed by AirTV's strategic partner, CMC Electronics. This antenna is a scaled version of CMC's Inmarsat Aero H antenna and is capable of scanning to 5 degrees above the horizon. Wide angle scanning up to 85 degrees from zenith is necessary for aircraft traversing the northernmost latitudes on transoceanic routes. AirTV has designed both the satellite coverage and aircraft antenna performance to ensure that high signal quality is maintained along all non-polar airline routes. AirTV will be the future of aeronautical broadband delivery. It has been designed specifically for global services and uses the ideal spectrum for this application. It will revolutionize the delivery of content to aircraft. This paper will describe the AirTV system and highlight its advanced service capabilities.

Tabu search algorithm for the distance-constrained vehicle routing problem with split deliveries by order.

PubMed

Xia, Yangkun; Fu, Zhuo; Pan, Lijun; Duan, Fenghua

2018-01-01

The vehicle routing problem (VRP) has a wide range of applications in the field of logistics distribution. In order to reduce the cost of logistics distribution, the distance-constrained and capacitated VRP with split deliveries by order (DCVRPSDO) was studied. We show that the customer demand, which can't be split in the classical VRP model, can only be discrete split deliveries by order. A model of double objective programming is constructed by taking the minimum number of vehicles used and minimum vehicle traveling cost as the first and the second objective, respectively. This approach contains a series of constraints, such as single depot, single vehicle type, distance-constrained and load capacity limit, split delivery by order, etc. DCVRPSDO is a new type of VRP. A new tabu search algorithm is designed to solve the problem and the examples testing show the efficiency of the proposed algorithm. This paper focuses on constructing a double objective mathematical programming model for DCVRPSDO and designing an adaptive tabu search algorithm (ATSA) with good performance to solving the problem. The performance of the ATSA is improved by adding some strategies into the search process, including: (a) a strategy of discrete split deliveries by order is used to split the customer demand; (b) a multi-neighborhood structure is designed to enhance the ability of global optimization; (c) two levels of evaluation objectives are set to select the current solution and the best solution; (d) a discriminating strategy of that the best solution must be feasible and the current solution can accept some infeasible solution, helps to balance the performance of the solution and the diversity of the neighborhood solution; (e) an adaptive penalty mechanism will help the candidate solution be closer to the neighborhood of feasible solution; (f) a strategy of tabu releasing is used to transfer the current solution into a new neighborhood of the better solution.

Tabu search algorithm for the distance-constrained vehicle routing problem with split deliveries by order

PubMed Central

Xia, Yangkun; Pan, Lijun; Duan, Fenghua

2018-01-01

The vehicle routing problem (VRP) has a wide range of applications in the field of logistics distribution. In order to reduce the cost of logistics distribution, the distance-constrained and capacitated VRP with split deliveries by order (DCVRPSDO) was studied. We show that the customer demand, which can’t be split in the classical VRP model, can only be discrete split deliveries by order. A model of double objective programming is constructed by taking the minimum number of vehicles used and minimum vehicle traveling cost as the first and the second objective, respectively. This approach contains a series of constraints, such as single depot, single vehicle type, distance-constrained and load capacity limit, split delivery by order, etc. DCVRPSDO is a new type of VRP. A new tabu search algorithm is designed to solve the problem and the examples testing show the efficiency of the proposed algorithm. This paper focuses on constructing a double objective mathematical programming model for DCVRPSDO and designing an adaptive tabu search algorithm (ATSA) with good performance to solving the problem. The performance of the ATSA is improved by adding some strategies into the search process, including: (a) a strategy of discrete split deliveries by order is used to split the customer demand; (b) a multi-neighborhood structure is designed to enhance the ability of global optimization; (c) two levels of evaluation objectives are set to select the current solution and the best solution; (d) a discriminating strategy of that the best solution must be feasible and the current solution can accept some infeasible solution, helps to balance the performance of the solution and the diversity of the neighborhood solution; (e) an adaptive penalty mechanism will help the candidate solution be closer to the neighborhood of feasible solution; (f) a strategy of tabu releasing is used to transfer the current solution into a new neighborhood of the better solution. PMID:29763419

Where are we on the diffusion curve? Trends and drivers of primary care physicians' use of health information technology.

PubMed

Audet, Anne-Marie; Squires, David; Doty, Michelle M

2014-02-01

To describe trends in primary care physicians' use of health information technology (HIT) between 2009 and 2012, examine practice characteristics associated with greater HIT capacity in 2012, and explore factors such as delivery system and payment reforms that may affect adoption and functionality. We used data from the 2012 and 2009 Commonwealth Fund International Health Policy Surveys of Primary Care Physicians. The data were collected in both years by postal mail between March and July among a nationally representative sample of primary care physicians in the United States. We compared primary care physicians' HIT capacity in 2009 and 2012. We employed multivariable logistic regression to analyze whether participating in an integrated delivery system, sharing resources and support with other practices, and being eligible for financial incentives were associated with greater HIT capacity in 2012. Primary care physicians' HIT capacity has significantly expanded since 2009, although solo practices continue to lag. Practices that are part of an integrated delivery system or share resources with other practices have higher rates of electronic medical record (EMR) adoption, multifunctional HIT, electronic information exchange, and electronic access for patients. Receiving or being eligible for financial incentives is associated with greater adoption of EMRs and information exchange. Federal efforts to increase adoption have coincided with a rapid increase in HIT capacity. Delivery system and payment reforms and federally funded extension programs could offer promising pathways for further diffusion. © Health Research and Educational Trust.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liun, Edwaren, E-mail: edwaren@batan.go.id; Suparman, E-mail: edwaren@batan.go.id

Regarding nuclear power plant development in Bangka Island, it can be estimated that produced power will be oversupply for the Bangka Island and needs to transmit to Sumatra or Java Island. The distance between the regions or islands causing considerable loss of power in transmission by alternating current, and a wide range of technical and economical issues. The objective of this paper addresses to economics analysis of direct current transmission system to overcome those technical problem. Direct current transmission has a stable characteristic, so that the power delivery from Bangka to Sumatra or Java in a large scale efficiently andmore » reliably can be done. HVDC system costs depend on the power capacity applied to the system and length of the transmission line in addition to other variables that may be different.« less

Cost estimation of HVDC transmission system of Bangka's NPP candidates

NASA Astrophysics Data System (ADS)

Liun, Edwaren; Suparman

2014-09-01

Regarding nuclear power plant development in Bangka Island, it can be estimated that produced power will be oversupply for the Bangka Island and needs to transmit to Sumatra or Java Island. The distance between the regions or islands causing considerable loss of power in transmission by alternating current, and a wide range of technical and economical issues. The objective of this paper addresses to economics analysis of direct current transmission system to overcome those technical problem. Direct current transmission has a stable characteristic, so that the power delivery from Bangka to Sumatra or Java in a large scale efficiently and reliably can be done. HVDC system costs depend on the power capacity applied to the system and length of the transmission line in addition to other variables that may be different.

Capacity planning for maternal-fetal medicine using discrete event simulation.

PubMed

Ferraro, Nicole M; Reamer, Courtney B; Reynolds, Thomas A; Howell, Lori J; Moldenhauer, Julie S; Day, Theodore Eugene

2015-07-01

Maternal-fetal medicine is a rapidly growing field requiring collaboration from many subspecialties. We provide an evidence-based estimate of capacity needs for our clinic, as well as demonstrate how simulation can aid in capacity planning in similar environments. A Discrete Event Simulation of the Center for Fetal Diagnosis and Treatment and Special Delivery Unit at The Children's Hospital of Philadelphia was designed and validated. This model was then used to determine the time until demand overwhelms inpatient bed availability under increasing capacity. No significant deviation was found between historical inpatient censuses and simulated censuses for the validation phase (p = 0.889). Prospectively increasing capacity was found to delay time to balk (the inability of the center to provide bed space for a patient in need of admission). With current capacity, the model predicts mean time to balk of 276 days. Adding three beds delays mean time to first balk to 762 days; an additional six beds to 1,335 days. Providing sufficient access is a patient safety issue, and good planning is crucial for targeting infrastructure investments appropriately. Computer-simulated analysis can provide an evidence base for both medical and administrative decision making in a complex clinical environment. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Implications of protein- and Peptide-based nanoparticles as potential vehicles for anticancer drugs.

PubMed

Elzoghby, Ahmed O; Elgohary, Mayada M; Kamel, Nayra M

2015-01-01

Protein-based nanocarriers have gained considerable attention as colloidal carrier systems for the delivery of anticancer drugs. Protein nanocarriers possess various advantages including their low cytotoxicity, abundant renewable sources, high drug-binding capacity, and significant uptake into the targeted tumor cells. Moreover, the unique protein structure offers the possibility of site-specific drug conjugation and tumor targeting using various ligands modifying the surface of protein nanocarriers. In this chapter, we highlight the most important applications of protein nanoparticles (NPs) for the delivery of anticancer drugs. We examine the various techniques that have been utilized for the preparation of anticancer drug-loaded protein NPs. Finally, the current chapter also reviews the major outcomes of the in vitro and in vivo investigations of surface-modified tumor-targeted protein NPs. © 2015 Elsevier Inc. All rights reserved.

Carbon nanotube uptake and toxicity in the brain.

PubMed

Zhang, Leying; Alizadeh, Darya; Badie, Behnam

2010-01-01

The development of novel drug delivery systems is essential for the improvement of therapeutics for most human diseases. Currently used cellular delivery systems, such as viral vectors, liposomes, cationic lipids, and polymers, may have limited clinical efficacy because of safety issues, low gene transfer efficiency, or cytotoxicity. Carbon nanotubes (CNTs) have garnered much interest as possible biological vectors after the recent discovery of their capacity to penetrate cells. Inspite of the prominence of CNT studies in the nanotechnology literature, exploration of their application to central nervous system (CNS) therapeutics is at a very early stage. Before CNTs are used for treatment of brain and spinal cord disorders, however, several issues such as their CNS penetration and toxicity need to be addressed. Here, we discuss methods by which CNT uptake and toxicity can be assessed in animal models.

Removal of uranium (VI) from aqueous systems by nanoscale zero-valent iron particles suspended in carboxy-methyl cellulose

NASA Astrophysics Data System (ADS)

Popescu (Hoştuc), Ioana-Carmen; Filip, Petru; Humelnicu, Doina; Humelnicu, Ionel; Scott, Thomas Bligh; Crane, Richard Andrew

2013-11-01

Carboxy-methyl-cellulose (CMC), a common "delivery vehicle" for the subsurface deployment of iron nanoparticles (INP) has been tested in the current work for the removal of aqueous uranium from synthetic water samples. A comparison of the removal of aqueous uranium from solutions using carboxy-methyl-cellulose with and without iron nanoparticles (CMC-INP and CMC, respectively) was tested over a 48 h reaction period. Analysis of liquid samples using spectrophotometry determined a maximum sorption capacity of uranium, Qmax, of 185.18 mg/g and 322.58 mg/g for CMC and CMC-INP respectively, providing strong evidence of an independent aqueous uranium removal ability exhibited by CMC. The results point out that CMC provides an additional capacity for aqueous uranium removal. Further tests are required to determine whether similar behaviour will be observed for other aqueous contaminant species and if the presence of CMC within a INP slurry inhibits or aids the reactivity, reductive capacity and affinity of INP for aqueous contaminant removal.

Pore-formation by adenylate cyclase toxoid activates dendritic cells to prime CD8+ and CD4+ T cells.

PubMed

Svedova, Martina; Masin, Jiri; Fiser, Radovan; Cerny, Ondrej; Tomala, Jakub; Freudenberg, Marina; Tuckova, Ludmila; Kovar, Marek; Dadaglio, Gilles; Adkins, Irena; Sebo, Peter

2016-04-01

The adenylate cyclase toxin-hemolysin (CyaA) of Bordetella pertussis is a bi-functional leukotoxin. It penetrates myeloid phagocytes expressing the complement receptor 3 and delivers into their cytosol its N-terminal adenylate cyclase enzyme domain (~400 residues). In parallel, ~1300 residue-long RTX hemolysin moiety of CyaA forms cation-selective pores and permeabilizes target cell membrane for efflux of cytosolic potassium ions. The non-enzymatic CyaA-AC(-) toxoid, has repeatedly been successfully exploited as an antigen delivery tool for stimulation of adaptive T-cell immune responses. We show that the pore-forming activity confers on the CyaA-AC(-) toxoid a capacity to trigger Toll-like receptor and inflammasome signaling-independent maturation of CD11b-expressing dendritic cells (DC). The DC maturation-inducing potency of mutant toxoid variants in vitro reflected their specifically enhanced or reduced pore-forming activity and K(+) efflux. The toxoid-induced in vitro phenotypic maturation of DC involved the activity of mitogen activated protein kinases p38 and JNK and comprised increased expression of maturation markers, interleukin 6, chemokines KC and LIX and granulocyte-colony-stimulating factor secretion, prostaglandin E2 production and enhancement of chemotactic migration of DC. Moreover, i.v. injected toxoids induced maturation of splenic DC in function of their cell-permeabilizing capacity. Similarly, the capacity of DC to stimulate CD8(+) and CD4(+) T-cell responses in vitro and in vivo was dependent on the pore-forming activity of CyaA-AC(-). This reveals a novel self-adjuvanting capacity of the CyaA-AC(-) toxoid that is currently under clinical evaluation as a tool for delivery of immunotherapeutic anti-cancer CD8(+) T-cell vaccines into DC.

The Current Status of Stem-Cell Therapy in Erectile Dysfunction: A Review

PubMed Central

Reed-Maldonado, Amanda B

2016-01-01

Stem cells are undifferentiated cells that are capable of renewal and repair of tissue due to their capacity for division and differentiation. The purpose of this review is to describe recent advances in the use of stem cell (SC) therapy for male erectile dysfunction (ED). We performed a MEDLINE database search of all relevant articles regarding the use of SCs for ED. We present a concise summary of the scientific principles behind the usage of SC for ED. We discuss the different types of SCs, delivery methods, current pre-clinical literature, and published clinical trials. Four clinical trials employing SC for ED have been published. These articles are summarized in this review. All four report improvements in ED after SC therapy. SC therapy remains under investigation for the treatment of ED. It is reassuring that clinical trials thus far have reported positive effects on erectile function and few adverse events. Safety and methodical concerns about SC acquisition, preparation and delivery remain and require continued investigation prior to wide-spread application of these methods. PMID:28053944

Impact of hydrogen refueling configurations and market parameters on the refueling cost of hydrogen

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reddi, Krishna; Elgowainy, Amgad; Rustagi, Neha

The cost of hydrogen in early fuel cell electric vehicle (FCEV) markets is dominated by the cost of refueling stations, mainly due to the high cost of refueling equipment, small station capacities, lack of economies of scale, and low utilization of the installed refueling capacity. Using the hydrogen delivery scenario analysis model (HDSAM), this study estimates the impacts of these factors on the refueling cost for different refueling technologies and configurations, and quantifies the potential reduction in future hydrogen refueling cost compared to today’s cost in the United States. The current hydrogen refueling station levelized cost, for a 200 kg/daymore » dispensing capacity, is in the range of 6–8 dollars/kg H 2 when supplied with gaseous hydrogen, and 8–9 dollars/kg H 2 for stations supplied with liquid hydrogen. After adding the cost of hydrogen production, packaging, and transportation to the station’s levelized cost, the current cost of hydrogen at dispensers for FCEVs in California is in the range of 13–15 dollars/kg H 2. The refueling station capacity utilization strongly influences the hydrogen refueling cost. The underutilization of station capacity in early FCEV markets, such as in California, results in a levelized station cost that is approximately 40% higher than it would be in a scenario where the station had been fully utilized since it began operating. In future mature hydrogen FCEV markets, with a large demand for hydrogen, the refueling station’s levelized cost can be reduced to 2 dollars/kg H 2 as a result of improved capacity utilization and reduced equipment cost via learning and economies of scale.« less

Impact of hydrogen refueling configurations and market parameters on the refueling cost of hydrogen

DOE PAGES

Reddi, Krishna; Elgowainy, Amgad; Rustagi, Neha; ...

2017-06-30

The cost of hydrogen in early fuel cell electric vehicle (FCEV) markets is dominated by the cost of refueling stations, mainly due to the high cost of refueling equipment, small station capacities, lack of economies of scale, and low utilization of the installed refueling capacity. Using the hydrogen delivery scenario analysis model (HDSAM), this study estimates the impacts of these factors on the refueling cost for different refueling technologies and configurations, and quantifies the potential reduction in future hydrogen refueling cost compared to today’s cost in the United States. The current hydrogen refueling station levelized cost, for a 200 kg/daymore » dispensing capacity, is in the range of 6–8 dollars/kg H 2 when supplied with gaseous hydrogen, and 8–9 dollars/kg H 2 for stations supplied with liquid hydrogen. After adding the cost of hydrogen production, packaging, and transportation to the station’s levelized cost, the current cost of hydrogen at dispensers for FCEVs in California is in the range of 13–15 dollars/kg H 2. The refueling station capacity utilization strongly influences the hydrogen refueling cost. The underutilization of station capacity in early FCEV markets, such as in California, results in a levelized station cost that is approximately 40% higher than it would be in a scenario where the station had been fully utilized since it began operating. In future mature hydrogen FCEV markets, with a large demand for hydrogen, the refueling station’s levelized cost can be reduced to 2 dollars/kg H 2 as a result of improved capacity utilization and reduced equipment cost via learning and economies of scale.« less

A new strategy to mitigate the initial capacity loss of lithium ion batteries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Su, Xin; Lin, Chikai; Wang, Xiaoping

2016-08-01

Hard carbon (non-graphitizable) and related materials, like tin, tin oxide, silicon, and silicon oxide, have a high theoretical lithium delivery capacity (>550 mAh/g depending on their structural and chemical properties) but unfortunately they also exhibit a large initial capacity loss (ICL) that overrides the true reversible capacity in a full cell. Overcoming the large ICL of hard carbon in a full-cell lithium-ion battery (LIB) necessitates a new strategy wherein a sacrificial lithium source additive, such as, Li5FeO4 (LFO), is inserted on the cathode side. Full batteries using hard carbon coupled with LFO-LiCoO2 (LCO) are currently under development at our laboratory.more » We find that the reversible capacity of a cathode containing LFO can be increased by 14%. Furthermore, the cycle performance of full cells with LFO additive is improved from <90% to >95%. We show that the LFO additive not only can address the irreversible capacity loss of the anode, but can also provide the additional lithium ion source required to mitigate the lithium loss caused by side reactions. In addition, we have explored the possibility to achieve higher capacity with hard carbon, whereby the energy density of full cells can be increased from ca. 300 Wh/kg to >400 Wh/kg.« less

The significance of transferrin receptors in oncology: the development of functional nano-based drug delivery systems.

PubMed

Tortorella, Stephanie; Karagiannis, Tom C

2014-01-01

Anticancer therapeutic research aims to improve clinical management of the disease through the development of strategies that involve currently-relevant treatment options and targeted delivery. Tumour-specific and -targeted delivery of compounds to the site of malignancy allows for enhanced cellular uptake, increased therapeutic benefit with high intratumoural drug concentrations, and decreased systemic exposure. Due to the upregulation of transferrin receptor expression in a wide variety of cancers, its function and its highly efficient recycling pathway, strategies involving the selective targeting of the receptor are well documented. Direct conjugation and immunotoxin studies using the transferrin peptide or anti-transferrin receptor antibodies as the targeting moiety have established the capacity to enhance cellular uptake, cross the blood brain barrier, limit systemic toxicity and reverse multi-drug resistance. Limitations in direct conjugation, including the difficulty in linking an adequate amount of therapeutic compound to the ligand or antibody have identified the requirement to develop novel delivery methods. The application of nanoparticulate theory in the development of functional drug delivery systems has proven to be most promising, with the ability to selectively modify size-dependent properties and surface chemistry. The transferrin modification on a range of nanoparticle formulations enhances selective cellular uptake through transferrin-mediated processes, and increases therapeutic benefit through the ability to encapsulate high concentrations of relevant drug to the tumour site. Although ineffective in crossing the blood brain barrier in its free form, chemotherapeutic compounds including doxorubicin, may be loaded into transferrin-conjugated nanocarriers and impart cytotoxic effects in glioma cells in vitro and in vivo. Additionally, transferrin-targeted nanoparticles may be used in selective diagnostic applications with enhanced selectivity and sensitivity. Four transferrin-modified nano-based drug delivery systems are currently in early phases of human clinical trials. Despite the collective promise, inconsistencies in some studies have exposed some limitations in current formulations and the difficulty in translating preliminary studies into clinically-relevant therapeutic options. The main objective of this review is to investigate the development of transferrin targeted nano-based drug delivery systems in order to establish the use of transferrin as a cancer-targeted moiety, and to ultimately evaluate the progression of cancer therapeutic strategies for future research.

Improving the United States airline industry's capacity to provide safe and dignified services to travelers with disabilities: focus group findings.

PubMed

McCarthy, Michael J

2011-01-01

As a component of a training development project for intercity air travel providers, we investigated the capacity of the airline industry to meet the needs of travelers with disabilities by exploring: (1) the level of sensitivity among personnel to travelers' needs, (2) training currently provided, (3) areas in which additional training might be beneficial, and (4) organisational/systems-level commitment to dignified assistance to all travelers. Forty-four airline/vendor employees participated in nine focus groups in four US cities. Groups were audio recorded and transcribed. A grounded-theory approach was used to develop a coding system which was then applied to transcripts to identify themes. Factors influencing capacity grouped broadly into four areas: characteristics of the job/system, characteristics of current training, characteristics of providers themselves, and characteristics of travelers. At an interpersonal level, providers were empathetic and desired to provide dignified services. They lacked training and adequate equipment in some cases, however, and organisational commitment varied between companies. Traveler characteristics were also shown to impact service delivery. Results are promising but additional regulatory and organisational policies are needed to ensure quality services. Providers and consumers of intercity air travel services may benefit from the findings and recommendations of this study.

Developing the public health workforce: training and recognizing specialists in public health from backgrounds other than medicine: experience in the UK.

PubMed

Gray, Selena F; Evans, David

2018-01-01

There is increasing recognition that improving health and tackling inequalities requires a strong public health workforce capable of delivering key public health functions across systems. The World Health Organization in Europe has identified securing the delivery of the Essential Public Health Operations and strengthening public health capacities within this as a priority.It is acknowledged that current public health capacities and arrangements of public health services vary considerably across the World Health Organization in European Region, and investment in multidisciplinary workforce with new skills is essential if public health services are to be delivered. This paper describes the current situation in the UK where there are nationally funded multidisciplinary programmes for training senior public health specialists. Uniquely, the UK provides public health registration for multidisciplinary as well as medical public health specialists. The transition from a predominantly medical to a multidisciplinary public health specialist workforce over a relatively short timescale is unprecedented globally and was the product of a sustained period of grass roots activism aligned with national policy innovation. the UK experience might provide a model for other countries seeking to develop public health specialist workforce capacity in line with the Essential Public Health Operations.

Barriers to Learners' Successful Completion of VET Flexible Delivery Programs.

ERIC Educational Resources Information Center

Grace, Lauri

In the early 1990s, Australian policymakers began explicitly promoting increased use of flexible delivery in vocational education and training (VET). Some researchers argued that many students lack the learning skills required to deal with the unique demands of flexible delivery. Concerns were also raised about the VET sector's capacity to help…

Spatial regulation of controlled bioactive factor delivery for bone tissue engineering

PubMed Central

Samorezov, Julia E.; Alsberg, Eben

2015-01-01

Limitations of current treatment options for critical size bone defects create a significant clinical need for tissue engineered bone strategies. This review describes how control over the spatiotemporal delivery of growth factors, nucleic acids, and drugs and small molecules may aid in recapitulating signals present in bone development and healing, regenerating interfaces of bone with other connective tissues, and enhancing vascularization of tissue engineered bone. State-of-the-art technologies used to create spatially controlled patterns of bioactive factors on the surfaces of materials, to build up 3D materials with patterns of signal presentation within their bulk, and to pattern bioactive factor delivery after scaffold fabrication are presented, highlighting their applications in bone tissue engineering. As these techniques improve in areas such as spatial resolution and speed of patterning, they will continue to grow in value as model systems for understanding cell responses to spatially regulated bioactive factor signal presentation in vitro, and as strategies to investigate the capacity of the defined spatial arrangement of these signals to drive bone regeneration in vivo. PMID:25445719

Structure of block copolymer micelles in the presence of co-solvents

NASA Astrophysics Data System (ADS)

Robertson, Megan; Wang, Shu; Le, Kim Mai; Piemonte, Rachele; Madsen, Louis

2015-03-01

Amphiphilic block copolymer micelles in water are under broad exploration for drug delivery applications due to their high loading capacity and targeted drug delivery. We aim to understand the kinetic and thermodynamic processes that underlie the self-assembly of diblock copolymer micelle systems. The present work focuses on diblock copolymers containing poly(ethylene oxide) (a hydrophilic polymer) and polycaprolactone (a hydrophobic polymer), which spontaneously self-assemble into spherical micelles in water. Addition of a common good solvent (a co-solvent) for both of the constituting blocks, such as tetrahydrofuran (THF), reduces the interfacial tension at the core-corona interface. We are currently investigating the effect of this phenomenon on the micelle structural properties, using scattering experiments and nuclear magnetic resonance. We have characterized the hydrodynamic radius, core radius, corona thickness, aggregation number, degree of swelling of the micelle core with the co-solvent, and unimer (free chain) concentration, as a function of the co-solvent concentration. Fundamental knowledge from these studies will inform design of drug delivery systems by allowing us to tailor micelle properties for optimal cargo loading.

Extrusion-spheronization: process variables and characterization.

PubMed

Sinha, V R; Agrawal, M K; Agarwal, A; Singh, G; Ghai, D

2009-01-01

Multiparticulate systems have undergone great development in the past decade fueled by the better understanding of their multiple roles as a suitable delivery system. With the passage of time, significant advances have been made in the process of pelletization due to the incorporation of specialized techniques for their development. Extrusion-spheronization seems to be the most promising process for the optimum delivery of many potent drugs having high systemic toxicity. It also offers immense pharmaceutical applicability due to the benefits of high loading capacity of active ingredient(s), narrow size distribution, and cost-effectiveness. On application of a specific coat, these systems can also aid in site-specific delivery, thereby enhancing the bioavailability of many drugs. The current review focuses on the process of extrusion-spheronization and the operational (extruder types, screen pressure, screw speed, temperature, moisture content, spheronization load, speed and time) and formulation (excipients and drugs) variables, which may affect the quality of the final pellets. Various methods for the evaluation of the quality of the pellets with regard to the size distribution, shape, friability, granule strength, density, porosity, flow properties, and surface texture are discussed.

Influencing the structure of block copolymer micelles with small molecule additives

NASA Astrophysics Data System (ADS)

Robertson, Megan; Singh, Avantika; Cooksey, Tyler; Kidd, Bryce; Piemonte, Rachele; Wang, Shu; Mai Le, Kim; Madsen, Louis

Amphiphilic block copolymer micelles in water are under broad exploration for drug delivery applications due to their high loading capacity and targeted drug delivery. We aim to understand the kinetic and thermodynamic processes that underlie the self-assembly of diblock copolymer micelle systems. The present work focuses on diblock copolymers containing poly(ethylene oxide) (a hydrophilic polymer) and polycaprolactone (a hydrophobic polymer), which spontaneously self-assemble into spherical micelles in water. Addition of a common good solvent (a co-solvent) for both of the constituting blocks, such as tetrahydrofuran (THF), reduces the interfacial tension at the core-corona interface. We are currently investigating the effect of this phenomenon on the micelle structural properties, using small-angle scattering and nuclear magnetic resonance. We have characterized the hydrodynamic radius, core radius, corona thickness, aggregation number, degree of swelling of the micelle core with the co-solvent, and unimer (free chain) concentration, as a function of the co-solvent concentration. Fundamental knowledge from these studies will inform design of drug delivery systems by allowing us to tailor micelle properties for optimal cargo loading.

Rational design of protamine nanocapsules as antigen delivery carriers.

PubMed

González-Aramundiz, José Vicente; Presas, Elena; Dalmau-Mena, Inmaculada; Martínez-Pulgarín, Susana; Alonso, Covadonga; Escribano, José M; Alonso, María J; Csaba, Noemi Stefánia

2017-01-10

Current challenges in global immunization indicate the demand for new delivery strategies, which could be applied to the development of new vaccines against emerging diseases, as well as to improve safety and efficacy of currently existing vaccine formulations. Here, we report a novel antigen nanocarrier consisting of an oily core and a protamine shell, further stabilized with pegylated surfactants. These nanocarriers, named protamine nanocapsules, were rationally designed to promote the intracellular delivery of antigens to immunocompetent cells and to trigger an efficient and long-lasting immune response. Protamine nanocapsules have nanometric size, positive zeta potential and high association capacity for H1N1 influenza hemagglutinin, a protein that was used here as a model antigen. The new formulation shows an attractive stability profile both, as an aqueous suspension or a freeze-dried powder formulation. In vitro studies showed that protamine nanocapsules were efficiently internalized by macrophages without eliciting significant toxicity. In vivo studies indicate that antigen-loaded nanocapsules trigger immune responses comparable to those achieved with alum, even when using significantly lower antigen doses, thus indicating their adjuvant properties. These promising in vivo data, alongside with their versatility for the loading of different antigens and oily immunomodulators and their excellent stability profile, make these nanocapsules a promising platform for the delivery of antigens. Protamine sulphate (PubChem SID: 7849283), Sodium Cholate (PubChem CID: 23668194), Miglyol (PubChem CID: 53471835), α tocopherol (PubChem CID: 14985), Tween® 20(PubChem CID: 443314), Tween® 80(PubChem CID: 5281955), TPGS (PubChem CID: 71406). Copyright © 2016 Elsevier B.V. All rights reserved.

Silica-based mesoporous nanoparticles for controlled drug delivery

PubMed Central

Kwon, Sooyeon; Singh, Rajendra K; Perez, Roman A; Abou Neel, Ensanya A

2013-01-01

Drug molecules with lack of specificity and solubility lead patients to take high doses of the drug to achieve sufficient therapeutic effects. This is a leading cause of adverse drug reactions, particularly for drugs with narrow therapeutic window or cytotoxic chemotherapeutics. To address these problems, there are various functional biocompatible drug carriers available in the market, which can deliver therapeutic agents to the target site in a controlled manner. Among the carriers developed thus far, mesoporous materials emerged as a promising candidate that can deliver a variety of drug molecules in a controllable and sustainable manner. In particular, mesoporous silica nanoparticles are widely used as a delivery reagent because silica possesses favourable chemical properties, thermal stability and biocompatibility. Currently, sol-gel-derived mesoporous silica nanoparticles in soft conditions are of main interest due to simplicity in production and modification and the capacity to maintain function of bioactive agents. The unique mesoporous structure of silica facilitates effective loading of drugs and their subsequent controlled release. The properties of mesopores, including pore size and porosity as well as the surface properties, can be altered depending on additives used to fabricate mesoporous silica nanoparticles. Active surface enables functionalisation to modify surface properties and link therapeutic molecules. The tuneable mesopore structure and modifiable surface of mesoporous silica nanoparticle allow incorporation of various classes of drug molecules and controlled delivery to the target sites. This review aims to present the state of knowledge of currently available drug delivery system and identify properties of an ideal drug carrier for specific application, focusing on mesoporous silica nanoparticles. PMID:24020012

Peer Education: Productive Engagement for Older African Americans in Recovery From Depression.

PubMed

Conner, Kyaien O; Gum, Amber; Johnson, Angela; Cadet, Tamara; Brown, Charlotte

2017-06-17

Older adults who have personal experience with the mental health service delivery system gain unique and potentially valuable insight from their treatment experiences. Research suggests that incorporating trained individuals in recovery from a mental illness (i.e., peer educators) into mental health service delivery roles results in substantial benefits for current mental health consumers, particularly for older adults and racial and ethnic minorities who may feel disenfranchised from the traditional mental health service delivery system. However, little research has examined the impact of participating in these activities on the peer educators themselves. This mixed methods study examines the experiences of 10 African American older adults in recovery from depression currently working as trained peer educators. Peer educators reported feeling more positive, feeling their lives had significantly improved, and feeling better in general due to their peer educator roles. This qualitative investigation highlights four unique themes that can explain the benefit of serving in this capacity (i.e., Community Engagement, Life Long Learning and Education, Mental Health Recovery and Productive Aging). This study suggests that serving has a peer educator has a number of beneficial outcomes for African American older adults in recovery from depression. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Advanced drug and gene delivery systems based on functional biodegradable polycarbonates and copolymers.

PubMed

Chen, Wei; Meng, Fenghua; Cheng, Ru; Deng, Chao; Feijen, Jan; Zhong, Zhiyuan

2014-09-28

Biodegradable polymeric nanocarriers are one of the most promising systems for targeted and controlled drug and gene delivery. They have shown several unique advantages such as excellent biocompatibility, prolonged circulation time, passive tumor targeting via the enhanced permeability and retention (EPR) effect, and degradation in vivo into nontoxic products after completing their tasks. The current biodegradable drug and gene delivery systems exhibit, however, typically low in vivo therapeutic efficacy, due to issues of low loading capacity, inadequate in vivo stability, premature cargo release, poor uptake by target cells, and slow release of therapeutics inside tumor cells. To overcome these problems, a variety of advanced drug and gene delivery systems has recently been designed and developed based on functional biodegradable polycarbonates and copolymers. Notably, polycarbonates and copolymers with diverse functionalities such as hydroxyl, carboxyl, amine, alkene, alkyne, halogen, azido, acryloyl, vinyl sulfone, pyridyldisulfide, and saccharide, could be readily obtained by controlled ring-opening polymerization. In this paper, we give an overview on design concepts and recent developments of functional polycarbonate-based nanocarriers including stimuli-sensitive, photo-crosslinkable, or active targeting polymeric micelles, polymersomes and polyplexes for enhanced drug and gene delivery in vitro and in vivo. These multifunctional biodegradable nanosystems might be eventually developed for safe and efficient cancer chemotherapy and gene therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

Psychiatric Advance Directives in India: What will the future hold?

PubMed

Ratnam, Ashutosh; Rudra, Abhijit; Chatterjee, K; Das, R C

2015-08-01

Psychiatric Advance Directives (PADs) have been incorporated into India's Mental Health Care Bill, 2013. This is the first time any form of Advance Directive stands to receive legal sanction in India. PADs have numerous theoretical and empirically tenable therapeutic and financial advantages. Western experiences have shown high acceptance for the concept among psychiatric patients, and illustrated that most stable patients with severe mental illness retain the capacity to frame PADs consistent with community practice standards. However active psychopathology does impair this capacity, and therein, current subjective assessments of competence performed by Physicians without objective instruments are often inaccurate. Though PADs champion patient autonomy, when applied and studied, they have shown little significant advantage-there is currently not enough data to support evidence-based universal recommendations for PADs. PADs as incorporated into the Mental Health Care Bill model on existing Western statutes, and though many of the strengths of earlier systems have been subsumed, so have several of the shortcomings. The risks, benefits and applicability of PADs in India are complicated by the social re-calibration of patient autonomy, mental-healthcare delivery system weaknesses, and the relatively peripheral role the Psychiatrist is mandated to play in the entire advance directive process. Treating patients within the framework of their pre-stated wishes will be a much more intricate and arduous task than most of modern Psychiatric practice in India, but the difficulties, obstacles and inevitable failures encountered will provide evidence of the delivery system's weaknesses and thereby contribute to its strength. Copyright © 2015 Elsevier B.V. All rights reserved.

Integrated Testing, Simulation and Analysis of Electric Drive Options for Medium-Duty Parcel Delivery Vehicles: Preprint

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ramroth, L. A.; Gonder, J.; Brooker, A.

2012-09-01

The National Renewable Energy Laboratory verified diesel-conventional and diesel-hybrid parcel delivery vehicle models to evaluate petroleum reduction and cost implications of plug-in hybrid gasoline and diesel variants. These variants are run on a field-data-derived design matrix to analyze the effects of drive cycle, distance, battery replacements, battery capacity, and motor power on fuel consumption and lifetime cost. Two cost scenarios using fuel prices corresponding to forecasted highs for 2011 and 2030 and battery costs per kilowatt-hour representing current and long-term targets compare plug-in hybrid lifetime costs with diesel conventional lifetime costs. Under a future cost scenario of $100/kWh battery energymore » and $5/gal fuel, plug-in hybrids are cost effective. Assuming a current cost of $700/kWh and $3/gal fuel, they rarely recoup the additional motor and battery cost. The results highlight the importance of understanding the application's drive cycle, daily driving distance, and kinetic intensity. For instances in the current-cost scenario where the additional plug-in hybrid cost is regained in fuel savings, the combination of kinetic intensity and daily distance travelled does not coincide with the usage patterns observed in the field data. If the usage patterns were adjusted, the hybrids could become cost effective.« less

Expanding services in a shrinking economy: desktop document delivery in a dental school library.

PubMed

Gushrowski, Barbara A

2011-07-01

How can library staff develop and promote a document delivery service and then expand the service to a wide audience? The setting is the library at the Indiana University School of Dentistry (IUSD), Indianapolis. A faculty survey and a citation analysis were conducted to determine potential use of the service. Volume of interlibrary loan transactions and staff and equipment capacity were also studied. IUSD Library staff created a desktop delivery service (DDSXpress) for faculty and then expanded the service to practicing dental professionals and graduate students. The number of faculty using DDSXpress remains consistent. The number of practicing dental professionals using the service is low. Graduate students have been quick to adopt the service. Through careful analysis of capacity and need for the service, staff successfully expanded document delivery service without incurring additional costs. Use of DDSXpress is continually monitored, and opportunities to market the service to practicing dental professionals are being investigated.

Modeling hospital surgical delivery process design using system simulation: optimizing patient flow and bed capacity as an illustration.

PubMed

Kumar, Sameer

2011-01-01

It is increasingly recognized that hospital operation is an intricate system with limited resources and many interacting sources of both positive and negative feedback. The purpose of this study is to design a surgical delivery process in a county hospital in the U.S where patient flow through a surgical ward is optimized. The system simulation modeling is used to address questions of capacity planning, throughput management and interacting resources which constitute the constantly changing complexity that characterizes designing a contemporary surgical delivery process in a hospital. The steps in building a system simulation model is demonstrated using an example of building a county hospital in a small city in the US. It is used to illustrate a modular system simulation modeling of patient surgery process flows. The system simulation model development will enable planners and designers how they can build in overall efficiencies in a healthcare facility through optimal bed capacity for peak patient flow of emergency and routine patients.

Cyclodextrin based nanosponges for pharmaceutical use: a review.

PubMed

Tejashri, Gursalkar; Amrita, Bajaj; Darshana, Jain

2013-09-01

Nanosponges are a novel class of hyper-crosslinked polymer based colloidal structures consisting of solid nanoparticles with colloidal sizes and nanosized cavities. These nano-sized colloidal carriers have been recently developed and proposed for drug delivery, since their use can solubilize poorly water-soluble drugs and provide prolonged release as well as improve a drug's bioavailability by modifying the pharmacokinetic parameters of actives. Development of nanosponges as drug delivery systems, with special reference to cyclodextrin based nanosponges, is presented in this article. In the current review, attempts have been made to illustrate the features of cyclodextrin based nanosponges and their applications in pharmaceutical formulations. Special emphasis has been placed on discussing the methods of preparation, characterization techniques and applications of these novel drug delivery carriers for therapeutic purposes. Nanosponges can be referred to as solid porous particles having a capacity to load drugs and other actives into their nanocavity; they can be formulated as oral, parenteral, topical or inhalation dosage forms. Nanosponges offer high drug loading compared to other nanocarriers and are thus suitable for solving issues related to stability, solubility and delayed release of actives. Controlled release of the loaded actives and solubility enhancement of poorly water-soluble drugs are major advantages of nanosponge drug delivery systems.

Drug delivery with topically applied nanoparticles: science fiction or reality.

PubMed

Lademann, J; Richter, H; Meinke, M C; Lange-Asschenfeldt, B; Antoniou, C; Mak, W C; Renneberg, R; Sterry, W; Patzelt, A

2013-01-01

The efficacy of topically applied drugs is determined by their action mechanism and their potential capacity of passing the skin barrier. Nanoparticles are assumed to be efficient carrier systems for drug delivery through the skin barrier. For flexible nanoparticles like liposomes, this effect has been well demonstrated. The penetration properties of solid nanoparticles are currently under intensive investigation. The crucial advantage of nanoparticles over non-particulate substances is their capability to penetrate deeply into the hair follicles where they can be stored for several days. There is no evidence, yet, that solid particles ≥40 nm are capable of passing through the healthy skin barrier. Therefore and in spite of the long-standing research efforts in this field, commercially available solid nanoparticle-based products for drug delivery through the healthy skin are still missing. Nevertheless, the prospects for the clinical use of nanoparticles in drug delivery are tremendous. They can be designed as transport systems delivering drugs efficiently into the hair follicles in the vicinity of specific target structures. Once deposited at these structures, specific signals might trigger the release of the drugs and exert their effects on the target cells. In this article, examples of such triggered drug release are presented. © 2013 S. Karger AG, Basel.

Formulation and evaluation of in situ gelling systems for intranasal administration of gastrodin.

PubMed

Cai, Zheng; Song, Xiangrong; Sun, Feng; Yang, Zhaoxiang; Hou, Shixiang; Liu, Zhongqiu

2011-12-01

Gastrodin is the major bioactive constituent of the traditional Chinese drug "Tianma." It is used in the treatment of some nervous system diseases and can be transported to the brain via intranasal administration. In the current paper, the development of a novel ion-activated in situ gelling system for the nasal delivery of gastrodin is discussed. An in situ perfusion model was used to determine the absorption-rate constant of gastrodin through rat nasal mucosa. The optimal formulation was determined by measuring the critical cation concentration, anti-dilution capacity, gel expansion coefficient, water-holding capacity, and adhesive capacity. The best formulation consisted of 10% gastrodin, 0.5% deacetylated gellan gum as the gelatinizer, and 0.03% ethylparaben as the preservative. The rheological properties of gastrodin nasal in situ gels were also investigated. The viscosity and elasticity sharply increased at temperatures below 25°C. When physiological concentrations of cations were added into the preparation, the mixture gelled into a semi-solid. The results of an accelerated stability test show that gastrodin nasal in situ gels can be stable for more than 2 years. Mucociliary toxicity was evaluated using the in situ toad palate model and the rat nasal mucociliary method; both models demonstrated no measurable ciliotoxicity. Pharmacodynamic studies suggest that similar acesodyne and sedative effects were induced following intranasal administration of 50 mg/kg gastrodin nasal in situ gels or oral administration of 100 mg/kg gastrodin solution. The in situ gel preparation is a safe and effective nasal delivery system for gastrodin.

Needleless coaxial electrospinning: A novel approach to mass production of coaxial nanofibers.

PubMed

Vysloužilová, Lucie; Buzgo, Matej; Pokorný, Pavel; Chvojka, Jiří; Míčková, Andrea; Rampichová, Michala; Kula, Jiří; Pejchar, Karel; Bílek, Martin; Lukáš, David; Amler, Evžen

2017-01-10

Herein, we describe a simple spinneret setup for needleless coaxial electrospinning that exceeds the limited production capacity of current approaches. The proposed weir spinneret enables coaxial electrospinning from free liquid surface. This approach leads to the formation of coaxial nanofibers with higher and uniform shell/core ratio, which results in the possibility of better tuning of the degradation rate. The throughput and quality increase favor the broader application of coaxial nanofibers from weir spinnerets as systems for controlled drug delivery in regenerative medicine and tissue engineering. Copyright © 2016 Elsevier B.V. All rights reserved.

Storage and network bandwidth requirements through the year 2000 for the NASA Center for Computational Sciences

NASA Technical Reports Server (NTRS)

Salmon, Ellen

1996-01-01

The data storage and retrieval demands of space and Earth sciences researchers have made the NASA Center for Computational Sciences (NCCS) Mass Data Storage and Delivery System (MDSDS) one of the world's most active Convex UniTree systems. Science researchers formed the NCCS's Computer Environments and Research Requirements Committee (CERRC) to relate their projected supercomputing and mass storage requirements through the year 2000. Using the CERRC guidelines and observations of current usage, some detailed projections of requirements for MDSDS network bandwidth and mass storage capacity and performance are presented.

Hibernation, a State of Natural Tolerance to Profound Reduction in Organ Blood Flow and Oxygen Delivery Capacity

DTIC Science & Technology

2001-01-01

reperfusion injury (Bolling et at., 1998). In our also inhil current experiments, pooled plasma samples from... bcl - 2 mediated mechanism. Clin. Immunol. Immunopathol. 89: 205-213. Ta Ruit, K.A., Broce, D.S., Chiang, ~~, Oeltgen, ~R., Welborn, J.R. and Nilekani, S...Publishers Ltd, Oxford. 23 .II . "’-C"",,""’’""’c""""""" ,,_. 5(3257’ 2 &80(17$7,213$*( )RUP$SSURYHG 20%1R 5(3257’$7( ’󈧄<<<<

Quality of basic maternal care functions in health facilities of five African countries: an analysis of national health system surveys.

PubMed

Kruk, Margaret E; Leslie, Hannah H; Verguet, Stéphane; Mbaruku, Godfrey M; Adanu, Richard M K; Langer, Ana

2016-11-01

Global efforts to increase births at health-care facilities might not reduce maternal or newborn mortality if quality of care is insufficient. However, little systematic evidence exists for the quality at health facilities caring for women and newborn babies in low-income countries. We analysed the quality of basic maternal care functions and its association with volume of deliveries and surgical capacity in health-care facilities in five sub-Saharan African countries. In this analysis, we combined nationally representative health system surveys (Service Provision Assessments by the Demographic and Health Survery Programme) with data for volume of deliveries and quality of delivery care from Kenya, Namibia, Rwanda, Tanzania, and Uganda. We measured the quality of basic maternal care functions in delivery facilities using an index of 12 indicators of structure and processes of care, including infrastructure and use of evidence-based routine and emergency care interventions. We regressed the quality index on volume of births and confounders (public or privately managed, availability of antiretroviral therapy services, availability of skilled staffing, and country) stratified by facility type: primary (no caesarean capacity) or secondary (has caesarean capacity) care facilities. The Harvard University Human Research Protection Program approved this analysis as exempt from human subjects review. The national surveys were completed between April, 2006, and May, 2010. Our sample consisted of 1715 (93%) of 1842 health-care facilities that provided normal delivery service, after exclusion of facilities with missing (n=126) or invalid (n=1) data. 1511 (88%) study facilities (site of 276 965 [44%] of 622 864 facility births) did not have caesarean section capacity (primary care facilities). Quality of basic maternal care functions was substantially lower in primary (index score 0·38) than secondary care facilities (0·77). Low delivery volume was consistently associated with poor quality, with differences in quality between the lowest versus highest volume facilities of -0·22 (95% CI -0·26 to -0·19) in primary care facilities and -0·17 (-0·21 to -0·11) in secondary care facilities. More than 40% of facility deliveries in these five African countries occurred in primary care facilities, which scored poorly on basic measures of maternal care quality. Facilities with caesarean section capacity, particularly those with birth volumes higher than 500 per year, had higher scores for maternal care quality. Low-income and middle-income countries should systematically assess and improve the quality of delivery care in health facilities to accelerate reduction of maternal and newborn deaths. None. Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND license. Published by Elsevier Ltd.. All rights reserved.

Preparation and characterization of carnauba wax nanostructured lipid carriers containing benzophenone-3.

PubMed

Lacerda, S P; Cerize, N N P; Ré, M I

2011-08-01

Nanostructured lipid carriers (NLCs) are potential active delivery systems based on mixtures of solid lipids and liquid oil. In this paper, aqueous dispersions of NLCs were prepared by a hot high-pressure homogenization technique using carnauba wax as the solid lipid and isodecyl oleate as the liquid oil. The preparation and stability parameters of benzophenone-3-loaded NLCs have been investigated concerning particle size, zeta potential and loading capacity to encapsulate benzophenone-3, a molecular sunscreen. The current investigation illustrates the effect of the composition of the lipid mixture on the entrapment efficiency, in vitro release and stability of benzophenone-3-loaded in these NLCs. A loading capacity of approximately 5% of benzophenone-3 (m(BZ-3) /m(lipids) ) was characteristic of these systems. © 2011 The Authors. ICS © 2011 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Water-resources optimization model for Santa Barbara, California

USGS Publications Warehouse

Nishikawa, Tracy

1998-01-01

A simulation-optimization model has been developed for the optimal management of the city of Santa Barbara's water resources during a drought. The model, which links groundwater simulation with linear programming, has a planning horizon of 5 years. The objective is to minimize the cost of water supply subject to: water demand constraints, hydraulic head constraints to control seawater intrusion, and water capacity constraints. The decision variables are montly water deliveries from surface water and groundwater. The state variables are hydraulic heads. The drought of 1947-51 is the city's worst drought on record, and simulated surface-water supplies for this period were used as a basis for testing optimal management of current water resources under drought conditions. The simulation-optimization model was applied using three reservoir operation rules. In addition, the model's sensitivity to demand, carry over [the storage of water in one year for use in the later year(s)], head constraints, and capacity constraints was tested.

Private sector approaches to workforce enhancement.

PubMed

Wendling, Wayne R

2010-06-01

This paper addresses the private practice model of dental care delivery in the US. The great majority of dental care services are delivered through this model and thus changes in the model represent a means to substantially change the supply and availability of dental services. The two main forces that change how private practices function are broad economic factors, which alter the demand for dental care and innovations in practice structure and function which alter the supply and cost of services. Economics has long recognized that although there are private market solutions for many issues, not all problems can be addressed through this model. The private practice of dentistry is a private market solution that works for a substantial share of the market. However, the private market may not work to resolve all issues associated with access and utilization. Solutions for some problems call for creative private - public arrangements - another form of innovation; and market-based solutions may not be feasible for each and every problem. This paper discusses these economic factors and innovation as they relate to the private practice of dentistry, with special emphasis on those elements that have increased the capacity of the dental practice to offer services to those with limited means to access fee-based care. Innovations are frequently described as new care delivery models or new workforce models. However, innovation can occur on an ongoing and regular basis as dental practices examine new ways to combine capital and human resources and to leverage the education and skill of the dentists to a greater number of patients. Innovation occurs within a market context as the current and projected economic returns reward the innovation. Innovation can also occur through private-public arrangements. There are indications of available capacity within the existing delivery system to expand service delivery. The Michigan Medicaid Healthy Kids Dental program is discussed as one example of how dental services to Medicaid insured children were effectively expanded using the private practice model.

In vitro and in vivo evaluation of poly(3,4-ethylenedioxythiophene)/poly(styrene sulfonate)/dopamine-coated electrodes for dopamine delivery.

PubMed

Sui, L; Song, X J; Ren, J; Cai, W J; Ju, L H; Wang, Y; Wang, L Y; Chen, M

2014-06-01

Poly(3,4-ethylenedioxythiophene) (PEDOT) doped with poly(styrene sulfonate) (PSS) has a variety of chemical and biomedical applications. The application of PEDOT/PSS polymers in drug delivery has attracted attention. However, whether conducting polymers of PEDOT/PSS could be used for dopamine delivery has not clear. In the present study, the PEDOT/PSS coatings incorporated with dopamine were fabricated on 0.5 mm diameter platinum electrodes, electrochemical properties, and dopamine delivery capacities of these electrodes were evaluated in vitro and in vivo through implanting these electrodes into brain striatum area. The findings demonstrated that the PEDOT/PSS/dopamine coatings on platinum electrodes could reduce electrodes impedances, increase charge storage capacities, and release significant levels of dopamine upon electrical stimulation of these electrodes. These results indicated that polymers of PEDOT/PSS/dopamine could be used for dopamine delivery, implicating potential application of PEDOT/PSS/dopamine-coated implantable electrodes in the treatment of some diseases associated with dopamine deficits, such as, electrodes for the treatment of Parkinson's disease during deep brain stimulation. Copyright © 2013 Wiley Periodicals, Inc.

Buccal drug delivery technologies for patient-centred treatment of radiation-induced xerostomia (dry mouth).

PubMed

Malallah, Osamah S; Garcia, Cristina M Aller; Proctor, Gordon B; Forbes, Ben; Royall, Paul G

2018-04-25

Radiotherapy is a life-saving treatment for head and neck cancers, but almost 100% of patients develop dry mouth (xerostomia) because of radiation-induced damage to their salivary glands. Patients with xerostomia suffer symptoms that severely affect their health as well as physical, social and emotional aspects of their life. The current management of xerostomia is the application of saliva substitutes or systemic delivery of saliva-stimulating cholinergic agents, including pilocarpine, cevimeline or bethanechol tablets. It is almost impossible for substitutes to replicate all the functional and sensory facets of natural saliva. Salivary stimulants are a better treatment option than saliva substitutes as the former induce the secretion of natural saliva from undamaged glands; typically, these are the minor salivary glands. However, patients taking cholinergic agents systemically experience pharmacology-related side effects including sweating, excessive lacrimation and gastrointestinal tract distresses. Local delivery direct to the buccal mucosa has the potential to provide rapid onset of drug action, i.e. activation of minor salivary glands within the buccal mucosa, while sparing systemic drug exposure and off-target effects. This critical review of the technologies for the local delivery of saliva-stimulating agents includes oral disintegrating tablets (ODTs), oral disintegrating films, medicated chewing gums and implantable drug delivery devices. Our analysis makes a strong case for the development of ODTs for the buccal delivery of cholinergic agents: these must be patient-friendly delivery platforms with variable loading capacities that release the drug rapidly in fluid volumes typical of residual saliva in xerostomia (0.05-0.1 mL). Copyright © 2018 Elsevier B.V. All rights reserved.

Micro- and nanobubbles: a versatile non-viral platform for gene delivery.

PubMed

Cavalli, Roberta; Bisazza, Agnese; Lembo, David

2013-11-18

Micro- and nanobubbles provide a promising non-viral strategy for ultrasound mediated gene delivery. Microbubbles are spherical gas-filled structures with a mean diameter of 1-8 μm, characterised by their core-shell composition and their ability to circulate in the bloodstream following intravenous injection. They undergo volumetric oscillations or acoustic cavitation when insonified by ultrasound and, most importantly, they are able to resonate at diagnostic frequencies. It is due to this behaviour that microbubbles are currently being used as ultrasound contrast agents, but their use in therapeutics is still under investigation. For example, microbubbles could play a role in enhancing gene delivery to cells: when combined with clinical ultrasound exposure, microbubbles are able to favour gene entry into cells by cavitation. Two different delivery strategies have been used to date: DNA can be co-administered with the microbubbles (i.e. the contrast agent) or 'loaded' in purposed-built bubble systems - indeed a number of different technological approaches have been proposed to associate genes within microbubble structures. Nanobubbles, bubbles with sizes in the nanometre order of magnitude, have also been developed with the aim of obtaining more efficient gene delivery systems. Their small sizes allow the possibility of extravasation from blood vessels into the surrounding tissues and ultrasound-targeted site-specific release with minimal invasiveness. In contrast, microbubbles, due to their larger sizes, are unable to extravasate, thus and their targeting capacity is limited to specific antigens present within the vascular lumen. This review provides an overview of the use of microbubbles as gene delivery systems, with a specific focus on recent research into the development of nanosystems. In particular, ultrasound delivery mechanisms, formulation parameters, gene-loading approaches and the advantages of nanometric systems will be described. Copyright © 2013 Elsevier B.V. All rights reserved.

Can India’s primary care facilities deliver? A cross-sectional assessment of the Indian public health system’s capacity for basic delivery and newborn services

PubMed Central

Leslie, Hannah H; Regan, Mathilda; Nambiar, Devaki; Kruk, Margaret E

2018-01-01

Objectives To assess input and process capacity for basic delivery and newborn (intrapartum care hereafter) care in the Indian public health system and to describe differences in facility capacity between rural and urban areas and across states. Design Cross-sectional study. Setting Data from the nationally representative 2012–2014 District Level Household and Facility Survey, which includes a census of community health centres (CHC) and sample of primary health centres (PHC) across 30 states and union territories in India. Participants 8536 PHCs and 4810 CHCs. Outcome measures We developed a summative index of 33 structural and process capacity items matching the Indian Public Health Standards for PHCs as a metric of minimum facility capacity for intrapartum care. We assessed differences in performance on this index across facility type and location. Results About 30% of PHCs and 5% of CHCs reported not offering any intrapartum care. Among those offering services, volumes were low: median monthly delivery volume was 8 (IQR=13) in PHCs and 41 (IQR=73) in CHCs. Both PHCs and CHCs failed to meet the national standards for basic intrapartum care capacity. Mean facility capacity was low in PHCs in both urban (0.64) and rural (0.63) areas, while in CHCs, capacity was slightly higher in urban areas (0.77vs0.74). Gaps were most striking in availability of skilled human resources and emergency obstetric services. Poor capacity facilities were more concentrated in the more impoverished states, with 37% of districts from these states receiving scores in the lowest third of the facility capacity index (<0.70), compared with 21% of districts otherwise. Conclusions Basic intrapartum care capacity in Indian public primary care facilities is weak in both rural and urban areas, especially lacking in the poorest states with worst health outcomes. Improving maternal and newborn health outcomes will require focused attention to quality measurement, accountability mechanisms and quality improvement. Policies to address deficits in skilled providers and emergency service availability are urgently required. PMID:29866726

Can India's primary care facilities deliver? A cross-sectional assessment of the Indian public health system's capacity for basic delivery and newborn services.

PubMed

Sharma, Jigyasa; Leslie, Hannah H; Regan, Mathilda; Nambiar, Devaki; Kruk, Margaret E

2018-06-04

To assess input and process capacity for basic delivery and newborn (intrapartum care hereafter) care in the Indian public health system and to describe differences in facility capacity between rural and urban areas and across states. Cross-sectional study. Data from the nationally representative 2012-2014 District Level Household and Facility Survey, which includes a census of community health centres (CHC) and sample of primary health centres (PHC) across 30 states and union territories in India. 8536 PHCs and 4810 CHCs. We developed a summative index of 33 structural and process capacity items matching the Indian Public Health Standards for PHCs as a metric of minimum facility capacity for intrapartum care. We assessed differences in performance on this index across facility type and location. About 30% of PHCs and 5% of CHCs reported not offering any intrapartum care. Among those offering services, volumes were low: median monthly delivery volume was 8 (IQR=13) in PHCs and 41 (IQR=73) in CHCs. Both PHCs and CHCs failed to meet the national standards for basic intrapartum care capacity. Mean facility capacity was low in PHCs in both urban (0.64) and rural (0.63) areas, while in CHCs, capacity was slightly higher in urban areas (0.77vs0.74). Gaps were most striking in availability of skilled human resources and emergency obstetric services. Poor capacity facilities were more concentrated in the more impoverished states, with 37% of districts from these states receiving scores in the lowest third of the facility capacity index (<0.70), compared with 21% of districts otherwise. Basic intrapartum care capacity in Indian public primary care facilities is weak in both rural and urban areas, especially lacking in the poorest states with worst health outcomes. Improving maternal and newborn health outcomes will require focused attention to quality measurement, accountability mechanisms and quality improvement. Policies to address deficits in skilled providers and emergency service availability are urgently required. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Titanium wire implants with nanotube arrays: A study model for localized cancer treatment.

PubMed

Kaur, Gagandeep; Willsmore, Tamsyn; Gulati, Karan; Zinonos, Irene; Wang, Ye; Kurian, Mima; Hay, Shelley; Losic, Dusan; Evdokiou, Andreas

2016-09-01

Adverse complications associated with systemic administration of anti-cancer drugs are a major problem in cancer therapy in current clinical practice. To increase effectiveness and reduce side effects, localized drug delivery to tumour sites requiring therapy is essential. Direct delivery of potent anti-cancer drugs locally to the cancer site based on nanotechnology has been recognised as a promising alternative approach. Previously, we reported the design and fabrication of nano-engineered 3D titanium wire based implants with titania (TiO2) nanotube arrays (Ti-TNTs) for applications such as bone integration by using in-vitro culture systems. The aim of present study is to demonstrate the feasibility of using such Ti-TNTs loaded with anti-cancer agent for localized cancer therapy using pre-clinical cancer models and to test local drug delivery efficiency and anti-tumour efficacy within the tumour environment. TNF-related apoptosis-inducing ligand (TRAIL) which has proven anti-cancer properties was selected as the model drug for therapeutic delivery by Ti-TNTs. Our in-vitro 2D and 3D cell culture studies demonstrated a significant decrease in breast cancer cell viability upon incubation with TRAIL loaded Ti-TNT implants (TRAIL-TNTs). Subcutaneous tumour xenografts were established to test TRAIL-TNTs implant performance in the tumour environment by monitoring the changes in tumour burden over a selected time course. TRAIL-TNTs showed a significant regression in tumour burden within the first three days of implant insertion at the tumour site. Based on current experimental findings these Ti-TNTs wire implants have shown promising capacity to load and deliver anti-cancer agents maintaining their efficacy for cancer treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Information Delivery Systems: The Future Is Here.

ERIC Educational Resources Information Center

O'Malley, Penelope Grenoble

1993-01-01

Looks at developments in information delivery (including new interactive media formats, vastly increased channel capacity for standard cable television, and the development of wireless cable and other distribution technologies) that are revolutionizing the communications industry. Raises questions about the role technical communicators are being…

SMART-1/CLEMENTINE Study of Humorum and Procellarum Basins

NASA Astrophysics Data System (ADS)

Carey, William; Foing, Bernard H.; Koschny, Detlef; Pio Rossi, Angelo; Josset, Jean-Luc

A study undertaken by ESA to define a European Reference Architecture for Space Exploration is due to be completed in September 2008. The development of this architecture over the past twelve months has identified a number of key capabilities, among them a lunar lander system, which could form the basis for Europe's contribution to the future exploration of space in collaboration with International Partners. The focus of this paper will be on the lunar lander system, and will present the results of an analysis of possible payloads that could be accommodated by the lander. As the industrial study is at the Phase 0 or Pre-Phase A level, the design of such a lander system is at a very early stage in its development, but an estimation of the payload capacity allows a general assessment of the types of possible payloads that could be carried, currently this capacity is estimated at 1.1 tonnes of gross payload mass to the lunar surface (assuming an Ariane 5 ECA launch). An important characteristic of the lunar lander is that it provides a versatile and flexible system for utilisation in a broad range of lunar missions which include: - Independent lunar exploration missions for science, technology demonstration and research. - Delivery of logistics and cargo to support human surface sortie missions. - Delivery of logistics to a lunar base/outpost. - Deployment of individual infrastructure elements in support of a lunar base/outpost. Based on the above different types of missions, a number of configurations of "reference payload" sets are in the process of being defined that cover specific exploration objectives related primarily to capability demonstration, exploration enabling research and enabled science. Aspects covered include: ISRU, robotics, mobility, human preparation, life science and geology. This paper will present the current status of definition of the Reference Payload sets.

Mesoporous biocompatible and acid-degradable magnetic colloidal nanocrystal clusters with sustainable stability and high hydrophobic drug loading capacity.

PubMed

Luo, Bin; Xu, Shuai; Luo, An; Wang, Wen-Rui; Wang, Shi-Long; Guo, Jia; Lin, Yao; Zhao, Dong-Yuan; Wang, Chang-Chun

2011-02-22

Fabrication of magnetic particles (MPs) with high magnetization and large surface area simultaneously is critical for the application of MPs in bioseparation and drug delivery but remains a challenge. In this article, we describe an unprecedented approach to synthesize mesoporous magnetic colloidal nanocrystal clusters (MCNCs) stabilized by poly(γ-glutamic acid) (PGA) with high magnetization, large surface area (136 m(2)/g) and pore volume (0.57 cm(3)/g), excellent colloidal stability, prominent biocompatibility, and acid degradability. This result provides the important step toward the construction of a new family of MCNCs and demonstrates its capacity in a "magnetic motor" drug delivery system. Here, as an example, we explore the applicability of as-prepared mesoporous MCNCs as hydrophobic drug delivery vehicles (paclitaxel as model drug), and the resultant loading capacity is as high as 35.0 wt %. The antitumor efficacy measured by MTT assay is significantly enhanced, compared with free drugs. Thus, combined with their inherent high magnetization, the mesoporous MCNCs pave the way for applying magnetic targeting drug carriers in antitumor therapeutics.

Intestine-Specific, Oral Delivery of Captopril/Montmorillonite: Formulation and Release Kinetics

PubMed Central

2011-01-01

The intercalation of captopril (CP) into the interlayers of montmorillonite (MMT) affords an intestine-selective drug delivery system that has a captopril-loading capacity of up to ca. 14 %w/w and which exhibits near-zero-order release kinetics. PMID:27502639

Expanding services in a shrinking economy: desktop document delivery in a dental school library

PubMed Central

Gushrowski, Barbara A

2011-01-01

Question: How can library staff develop and promote a document delivery service and then expand the service to a wide audience? Setting: The setting is the library at the Indiana University School of Dentistry (IUSD), Indianapolis. Method: A faculty survey and a citation analysis were conducted to determine potential use of the service. Volume of interlibrary loan transactions and staff and equipment capacity were also studied. Main results: IUSD Library staff created a desktop delivery service (DDSXpress) for faculty and then expanded the service to practicing dental professionals and graduate students. The number of faculty using DDSXpress remains consistent. The number of practicing dental professionals using the service is low. Graduate students have been quick to adopt the service. Conclusion: Through careful analysis of capacity and need for the service, staff successfully expanded document delivery service without incurring additional costs. Use of DDSXpress is continually monitored, and opportunities to market the service to practicing dental professionals are being investigated. PMID:21753911

Experiments and synthesis of bone-targeting epirubicin with the water-soluble macromolecular drug delivery systems of oxidized-dextran.

PubMed

Yu, Li; Cai, Lin; Hu, Hao; Zhang, Yi

2014-05-01

Epirubicin (EPI) is a broad spectrum antineoplastic drug, commonly used as a chemotherapy method to treat osteosarcoma. However, its application has been limited by many side-effects. Therefore, targeted drug delivery to bone has been the aim of current anti-bone-tumor drug studies. Due to the exceptional affinity of Bisphosphonates (BP) to bone, 1-amino-ethylene-1, 1-dephosphate acid (AEDP) was chosen as the bone targeting moiety for water-soluble macromolecular drug delivery systems of oxidized-dextran (OXD) to transport EPI to bone in this article. The bone targeting drug of AEDP-OXD-EPI was designed for the treatment of malignant bone tumors. The successful conjugation of AEDP-OXD-EPI was confirmed by analysis of FTIR and (1)H-NMR spectra. To study the bone-seeking potential of AEDP-OXD-EPI, an in vitro hydroxyapatite (HAp) binding assay and an in vivo experiment of bone-targeting capacity were established. The effectiveness of AEDP-OXD-EPI was demonstrated by inducing apoptosis and necrosis of MG-63 tumor cell line. The obtained experimental data indicated that AEDP-OXD-EPI is an ideal bone-targeting anti-tumor drug.

Natural material-decorated mesoporous silica nanoparticle container for multifunctional membrane-controlled targeted drug delivery

PubMed Central

Hu, Yan; Ke, Lei; Chen, Hao; Zhuo, Ma; Yang, Xinzhou; Zhao, Dan; Zeng, Suying; Xiao, Xincai

2017-01-01

To avoid the side effects caused by nonspecific targeting, premature release, weak selectivity, and poor therapeutic efficacy of current nanoparticle-based systems used for drug delivery, we fabricated natural material-decorated nanoparticles as a multifunctional, membrane-controlled targeted drug delivery system. The nanocomposite material coated with a membrane was biocompatible and integrated both specific tumor targeting and responsiveness to stimulation, which improved transmission efficacy and controlled drug release. Mesoporous silica nanoparticles (MSNs), which are known for their biocompatibility and high drug-loading capacity, were selected as a model drug container and carrier. The membrane was established by the polyelectrolyte composite method from chitosan (CS) which was sensitive to the acidic tumor microenvironment, folic acid-modified CS which recognizes the folate receptor expressed on the tumor cell surface, and a CD44 receptor-targeted polysaccharide hyaluronic acid. We characterized the structure of the nanocomposite as well as the drug release behavior under the control of the pH-sensitive membrane switch and evaluated the antitumor efficacy of the system in vitro. Our results provide a basis for the design and fabrication of novel membrane-controlled nanoparticles with improved tumor-targeting therapy. PMID:29200852

Vaccine Adjuvant Incorporation Strategy Dictates Peptide Amphiphile Micelle Immunostimulatory Capacity.

PubMed

Zhang, Rui; Kramer, Jake S; Smith, Josiah D; Allen, Brittany N; Leeper, Caitlin N; Li, Xiaolei; Morton, Logan D; Gallazzi, Fabio; Ulery, Bret D

2018-06-01

Current vaccine research has shifted from traditional vaccines (i.e., whole-killed or live-attenuated) to subunit vaccines (i.e., protein, peptide, or DNA) as the latter is much safer due to delivering only the bioactive components necessary to produce a desirable immune response. Unfortunately, subunit vaccines are very weak immunogens requiring delivery vehicles and the addition of immunostimulatory molecules termed adjuvants to convey protective immunity. An interesting type of delivery vehicle is peptide amphiphile micelles (PAMs), unique biomaterials where the vaccine is part of the nanomaterial itself. Due to the modularity of PAMs, they can be readily modified to deliver both vaccine antigens and adjuvants within a singular construct. Through the co-delivery of a model antigenic epitope (Ovalbumin 319-340 -OVA BT ) and a known molecular adjuvant (e.g., 2,3-dipalmitoyl-S-glyceryl cysteine-Pam 2 C), greater insight into the mechanisms by which PAMs can exert immunostimulatory effects was gained. It was found that specific combinations of antigen and adjuvant can significantly alter vaccine immunogenicity both in vitro and in vivo. These results inform fundamental design rules that can be leveraged to fabricate optimal PAM-based vaccine formulations for future disease-specific applications. Graphical Abstract.

Moving from data collection to application: a systematic literature review of surgical capacity assessments and their applications.

PubMed

Carlson, Lucas C; Lin, Joseph A; Ameh, Emmanuel A; Mulwafu, Wakisa; Donkor, Peter; Derbew, Miliard; Rodas, Edgar; Mkandawire, Nyengo C; Dhanaraj, Mitra; Yangni-Angate, Herve; Sani, Rachid; Labib, Mohamed; Barbero, Roxana; Clarke, Damian; Smith, Martin D; Sherman, Lawrence; Mutyaba, Frederick A; Alexander, Philip; Hadley, Larry G P; VanRooyen, Michael J; Kushner, Adam L

2015-04-01

Over the past decade, assessments of surgical capacity in low- and middle-income countries (LMICs) have contributed to our understanding of barriers to the delivery of surgical services in a number of countries. It is yet unclear, however, how the findings of these assessments have been applied and built upon within the published literature. A systematic literature review of surgical capacity assessments in LMICs was performed to evaluate current levels of understanding of global surgical capacity and to identify areas for future study. A reverse snowballing method was then used to follow-up citations of the identified studies to assess how this research has been applied and built upon in the literature. Twenty-one papers reporting the findings of surgical capacity assessments conducted in 17 different LMICs in South Asia, East Asia and Pacific, Latin America and the Caribbean, and sub-Saharan Africa were identified. These studies documented substantial deficits in human resources, infrastructure, equipment, and supplies. Only seven additional papers were identified which applied or built upon the studies. Among these, capacity assessment findings were most commonly used to develop novel tools and intervention strategies, but they were also used as baseline measurements against which updated capacity assessments were compared. While the global surgery community has made tremendous progress in establishing baseline values of surgical capacity in LMICs around the world, further work is necessary to build upon and apply the foundational knowledge established through these efforts. Capacity assessment data should be coordinated and used in ongoing research efforts to monitor and evaluate progress in global surgery and to develop targeted intervention strategies. Intervention strategy development may also be further incorporated into the evaluation process itself.

Horses for Courses: Moving India towards Universal Health Coverage through Targeted Policy Design.

PubMed

Maurya, Dayashankar; Virani, Altaf; Rajasulochana, S

2017-12-01

The debate on how India's health system should move towards universal health coverage was (meant to be) put to rest by the recent National Health Policy 2017. However, the new policy is silent about tackling bottlenecks mentioned in the said policy proposal. It aims to provide universal access to free primary care by strengthening the public system, and to secondary and tertiary care through strategic purchasing from the private sector, to overcome deficiencies in public provisioning in the short run. Yet, in doing so, it ignores critical factors needed to replicate successful models of public healthcare delivery from certain states that it hopes to emulate. The policy also overestimates the capacity of the public sector and downplays the challenges observed in purchasing secondary care. Drawing from literature in policy design, we emphasize that primary, secondary and tertiary care have distinct characteristics, and their provision requires separate approaches or policy tools depending on the context. Public provisioning, contract purchasing and insurance mechanisms are different policy tools that have to be matched with the context and characteristics of the policy arena. Given the current challenges of India's health system, we argue that tertiary care services are most suitable for insurance-based purchasing, while the public sector should concentrate on building the required capacities to dominate the provisioning of secondary care and fill gaps in primary care delivery, for India to achieve its universal coverage ambitions.

High-capacity and security molecular capsule transporters.

PubMed

Visessamit, Jakkapol; Kulsirirat, Kathawut; Yupapin, Preecha P

2015-01-01

Multiwavelength optical capsules can be generated and controlled by using soliton/Gaussian pulses within a nonlinear device system known as a "PANDA" ring circuit and system. The security of molecule/drug transportation can be formed by the strong coupling of soliton-like pulse, where the high-capacity optical capsules can be formed using the multiwavelength solitons, which can be a good advantage and combination of drug delivery to the required targets. Moreover, the multiple access of drug delivery can be formed using the optical networks, which allows the use of various drug molecules with variety of diagnosis and therapeutic applications.

A Capacity Forecast Model for Volatile Data in Maintenance Logistics

NASA Astrophysics Data System (ADS)

Berkholz, Daniel

2009-05-01

Maintenance, repair and overhaul processes (MRO processes) are elaborate and complex. Rising demands on these after sales services require reliable production planning and control methods particularly for maintaining valuable capital goods. Downtimes lead to high costs and an inability to meet delivery due dates results in severe contract penalties. Predicting the required capacities for maintenance orders in advance is often difficult due to unknown part conditions unless the goods are actually inspected. This planning uncertainty results in extensive capital tie-up by rising stock levels within the whole MRO network. The article outlines an approach to planning capacities when maintenance data forecasting is volatile. It focuses on the development of prerequisites for a reliable capacity planning model. This enables a quick response to maintenance orders by employing appropriate measures. The information gained through the model is then systematically applied to forecast both personnel capacities and the demand for spare parts. The improved planning reliability can support MRO service providers in shortening delivery times and reducing stock levels in order to enhance the performance of their maintenance logistics.

FHWA Research and Technology Evaluation: Public-Private Partnership Capacity Building Program

DOT National Transportation Integrated Search

2018-02-01

This report details the evaluation of the Federal Highway Administrations Office of Innovative Program Delivery Public-Private Partnership (P3) Capacity Building Program (P3 Program). The evaluators focused on the P3 Programs P3 Toolkit as an e...

Systems Analysis and Structural Design of an Unpressurized Cargo Delivery Vehicle

NASA Technical Reports Server (NTRS)

Wu, K. Chauncey; Cruz, Jonathan N.; Antol, Jeffrey; Sasamoto, Washito A.

2007-01-01

The International Space Station will require a continuous supply of replacement parts for ongoing maintenance and repair after the planned retirement of the Space Shuttle in 2010. These parts are existing line-replaceable items collectively called Orbital Replacement Units, and include heavy and oversized items such as Control Moment Gyroscopes and stowed radiator arrays originally intended for delivery aboard the Space Shuttle. Current resupply spacecraft have limited to no capability to deliver these external logistics. In support of NASA's Exploration Systems Architecture Study, a team at Langley Research Center designed an Unpressurized Cargo Delivery Vehicle to deliver bulk cargo to the Space Station. The Unpressurized Cargo Delivery Vehicle was required to deliver at least 13,200 lbs of cargo mounted on at least 18 Flight Releasable Attachment Mechanisms. The Crew Launch Vehicle design recommended in the Exploration Systems Architecture Study would be used to launch one annual resupply flight to the International Space Station. The baseline vehicle design developed here has a cargo capacity of 16,000 lbs mounted on up to 20 Flight Releasable Attachment Mechanisms. Major vehicle components are a 5.5m-diameter cargo module containing two detachable cargo pallets with the payload, a Service Module to provide propulsion and power, and an aerodynamic nose cone. To reduce cost and risk, the Service Module is identical to the one used for the Crew Exploration Vehicle design.

Argpyrimidine-tagged rutin-encapsulated biocompatible (ethylene glycol dimers) nanoparticles: Synthesis, characterization and evaluation for targeted drug delivery.

PubMed

Bhattacherjee, Abhishek; Dhara, Kaliprasanna; Chakraborti, Abhay Sankar

2016-07-25

Diabetes mellitus represents a major metabolic disorder affecting millions of people all over the world. Currently available therapeutic treatments are not good enough to control the long-term complications of diabetes. Active targeting via inclusion of a specific ligand on the nanoparticles provides effective therapeutic approach in different diseases. However, such specific drug delivery systems have not been explored much in diabetes due to lack of suitable biological targets in this disorder. Our objective is to synthesize a ligand-tagged drug-loaded nanoparticle for delivery of the drug at specific sites to enhance its therapeutic efficiency in diabetic condition. The nanoparticles have been prepared by using biocompatible ethylene glycol-bis (succinic acid N-hydroxysuccinimide ester) dimers. Although advanced glycation end products (AGEs) are the root causes of diabetic complications, argpyrimidine, an AGE, possesses antioxidant and reducing activities. AGE interacts selectively with its cell surface receptors (RAGE), which are significantly increased in diabetic condition. We have selected RAGE as the target of argpyrimidine, which is tagged on the nanoparticles as a ligand. Rutin, having anti-hyperglycemic and anti-glycating activities, has been used for nanoencapsulation. Rutin-loaded argpyrimidine-tagged nanoparticles have been synthesized and characterized. We have demonstrated the drug releasing capacity and target specificity of the synthesised drug delivery system under ex vivo and in vivo conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

You pray to your God: A qualitative analysis of challenges in the provision of safe, timely, and affordable surgical care in Uganda.

PubMed

Albutt, Katherine; Yorlets, Rachel R; Punchak, Maria; Kayima, Peter; Namanya, Didacus B; Anderson, Geoffrey A; Shrime, Mark G

2018-01-01

Five billion people lack access to safe, affordable, and timely surgical and anesthesia care. Significant challenges remain in the provision of surgical care in low-resource settings. Uganda is no exception. From September to November 2016, we conducted a mixed-methods countrywide surgical capacity assessment at 17 randomly selected public hospitals in Uganda. Researchers conducted 35 semi-structured interviews with key stakeholders to understand factors related to the provision of surgical care. The framework approach was used for thematic and explanatory data analysis. The Ugandan public health care sector continues to face significant challenges in the provision of safe, timely, and affordable surgical care. These challenges can be broadly grouped into preparedness and policy, service delivery, and the financial burden of surgical care. Hospital staff reported challenges including: (1) significant delays in accessing surgical care, compounded by a malfunctioning referral system; (2) critical workforce shortages; (3) operative capacity that is limited by inadequate infrastructure and overwhelmed by emergency and obstetric volume; (4) supply chain difficulties pertaining to provision of essential medications, equipment, supplies, and blood; (5) significant, variable, and sometimes catastrophic expenditures for surgical patients and their families; and (6) a lack of surgery-specific policies and priorities. Despite these challenges, innovative strategies are being used in the public to provide surgical care to those most in need. Barriers to the provision of surgical care are cross-cutting and involve constraints in infrastructure, service delivery, workforce, and financing. Understanding current strengths and shortfalls of Uganda's surgical system is a critical first step in developing effective, targeted policy and programming that will build and strengthen its surgical capacity.

Computational discovery of metal-organic frameworks with high gas deliverable capacity

NASA Astrophysics Data System (ADS)

Bao, Yi

Metal-organic frameworks (MOFs) are a rapidly emerging class of nanoporous materials with largely tunable chemistry and diverse applications in gas storage, gas purification, catalysis, sensing and drug delivery. Efforts have been made to develop new MOFs with desirable properties both experimentally and computationally for decades. To guide experimental synthesis, we here develop a computational methodology to explore MOFs with high gas deliverable capacity. This de novo design procedure applies known chemical reactions, considers synthesizability and geometric requirements of organic linkers, and efficiently evolves a population of MOFs to optimize a desirable property. We identify 48 MOFs with higher methane deliverable capacity at 65-5.8 bar condition than the MOF-5 reference in nine networks. In a more comprehensive work, we predict two sets of MOFs with high methane deliverable capacity at a 65-5.8 bar loading-delivery condition or a 35-5.8 bar loading-delivery condition. We also optimize a set of MOFs with high methane accessible internal surface area to investigate the relationship between deliverable capacities and internal surface area. This methodology can be extended to MOFs with multiple types of linkers and multiple SBUs. Flexibile MOFs may allow for sophisticated heat management strategies and also provide higher gas deliverable capacity than rigid frameworks. We investigate flexible MOFs, such as MIL-53 families, and Fe(bdp) and Co(bdp) analogs, to understand the structural phase transition of frameworks and the resulting influence on heat of adsorption. Challenges of simulating a system with a flexible host structure and incoming guest molecules are discussed. Preliminary results from isotherm simulation using the hybrid MC/MD simulation scheme on MIL-53(Cr) are presented. Suggestions for proceeding to understand the free energy profile of flexible MOFs are provided.

Fabrication of functional hollow microspheres constructed from MOF shells: Promising drug delivery systems with high loading capacity and targeted transport

PubMed Central

Gao, Xuechuan; Hai, Xiao; Baigude, Huricha; Guan, Weihua; Liu, Zhiliang

2016-01-01

An advanced multifunctional, hollow metal-organic framework (MOF) drug delivery system with a high drug loading level and targeted delivery was designed and fabricated for the first time and applied to inhibit tumour cell growth. This hollow MOF targeting drug delivery system was prepared via a simple post-synthetic surface modification procedure, starting from hollow ZIF-8 successfully obtained for the first time via a mild phase transformation under solvothermal conditions. As a result, the hollow ZIF-8 exhibits a higher loading capacity for the model anticancer drug 5-fluorouracil (5-FU). Subsequently, 5-FU-loaded ZIF-8 was encapsulated into polymer layers (FA-CHI-5-FAM) with three components: a chitosan (CHI) backbone, the imaging agent 5-carboxyfluorescein (5-FAM), and the targeting reagent folic acid (FA). Thus, an advanced drug delivery system, ZIF-8/5-FU@FA-CHI-5-FAM, was fabricated. A cell imaging assay demonstrated that ZIF-8/5-FU@FA-CHI-5-FAM could target and be taken up by MGC-803 cells. Furthermore, the as-prepared ZIF-8/5-FU@FA-CHI-5-FAM exhibited stronger cell growth inhibitory effects on MGC-803 cells because of the release of 5-FU, as confirmed by a cell viability assay. In addition, a drug release experiment in vitro indicated that ZIF-8/5-FU@FA-CHI-5-FAM exhibited high loading capacity (51%) and a sustained drug release behaviour. Therefore, ZIF-8/5-FU@FA-CHI-5-FAM could provide targeted drug transportation, imaging tracking and localized sustained release. PMID:27876876

Evaluation of critical formulation parameters in design and differentiation of self-microemulsifying drug delivery systems (SMEDDSs) for oral delivery of aciclovir.

PubMed

Janković, Jovana; Djekic, Ljiljana; Dobričić, Vladimir; Primorac, Marija

2016-01-30

The study investigated the influence of formulation parameters for design of self-microemulsifying drug delivery systems (SMEDDSs) comprising oil (medium chain triglycerides) (10%), surfactant (Labrasol(®), polysorbate 20, or Kolliphor(®) RH40), cosurfactant (Plurol(®) Oleique CC 497) (q.s. ad 100%), and cosolvent (glycerol or macrogol 400) (20% or 30%), and evaluate their potential as carriers for oral delivery of a poorly permeable antivirotic aciclovir (acyclovir). The drug loading capacity of the prepared formulations ranged from 0.18-31.66 mg/ml. Among a total of 60 formulations, three formulations meet the limits for average droplet size (Z-ave) and polydispersity index (PdI) that have been set for SMEDDSs (Z-ave≤100nm, PdI<0.250) upon spontaneous dispersion in 0.1M HCl and phosphate buffer pH 7.2. SMEDDSs with the highest aciclovir loading capacity (24.06 mg/ml and 21.12 mg/ml) provided the in vitro drug release rates of 0.325 mg cm(-2)min(-1) and 0.323 mg cm(-2)min(-1), respectively, and significantly enhanced drug permeability in the parallel artificial membrane permeability assay (PAMPA), in comparison with the pure drug substance. The results revealed that development of SMEDDSs with enhanced drug loading capacity and oral delivery potential, required optimization of hydrophilic ingredients, in terms of size of hydrophilic moiety of the surfactant, surfactant-to-cosurfactant mass ratio (Km), and log P of the cosolvent. Copyright © 2015 Elsevier B.V. All rights reserved.

Quantitative measurement of delivery and gene silencing activities of siRNA polyplexes containing pyridylthiourea-grafted polyethylenimines.

PubMed

Pinel, Sophie; Aman, Emmanuel; Erblang, Felix; Dietrich, Jonathan; Frisch, Benoit; Sirman, Julien; Kichler, Antoine; Sibler, Annie-Paule; Dontenwill, Monique; Schaffner, Florence; Zuber, Guy

2014-05-28

The activity of synthetic interfering nucleic acids (siRNAs) relies on the capacity of delivery systems to efficiently transport nucleic acids into the cytosol of target cells. The pyridylthiourea-grafted 25KDa polyethylenimine (πPEI) is an excellent carrier for siRNA delivery into cells and it was extensively investigated in this report. Quantification of the siRNA-mediated gene silencing efficiency indicated that the πPEI specific delivery activity at the cell level may be measured and appears relatively constant in various cell lines. Delivery experiments assaying inhibitors of various entry pathways or concanamycin A, an inhibitor of the H(+)/ATPase vacuolar pump showed that the πPEI/siRNA polyplexes did not require any specific entry mode but strongly relied on vacuolar acidification for functional siRNA delivery. Next, πPEI polyplexes containing a siRNA targeting the transcription factor HIF-1α, known to be involved in tumor progression, were locally injected into mice xenografted with a human glioblastoma. A 55% reduction of the level of the target mRNA was observed at doses comparable to those used in vitro when the πPEI delivery activity was calculated per cell. Altogether, our study underscores the usefulness of "simple"/rough cationic polymers for siRNA delivery despite their intrinsic limitations. The study underscores as well as that bottom-up strategies make sense. The in vitro experiments can precede in vivo administration and be of high value for selection of the carrier with enhanced specific delivery activity and parallel other research aiming at improving synthetic delivery systems for resilience in the blood and for enhanced tissue-targeting capacity. Copyright © 2014 Elsevier B.V. All rights reserved.

Nanoparticle-Hydrogel: A Hybrid Biomaterial System for Localized Drug Delivery

PubMed Central

Gao, Weiwei; Zhang, Yue; Zhang, Qiangzhe; Zhang, Liangfang

2016-01-01

Nanoparticles have offered a unique set of properties for drug delivery including high drug loading capacity, combinatorial delivery, controlled and sustained drug release, prolonged stability and lifetime, and targeted delivery. To further enhance therapeutic index, especially for localized application, nanoparticles have been increasingly combined with hydrogels to form a hybrid biomaterial system for controlled drug delivery. Herein, we review recent progresses in engineering such nanoparticle-hydrogel hybrid system (namely ‘NP-gel’) with a particular focus on its application for localized drug delivery. Specifically, we highlight four research areas where NP-gel has shown great promises, including (1) passively controlled drug release, (2) stimuli-responsive drug delivery, (3) site-specific drug delivery, and (4) detoxification. Overall, integrating therapeutic nanoparticles with hydrogel technologies creates a unique and robust hybrid biomaterial system that enables effective localized drug delivery. PMID:26951462

Robust Lentiviral Gene Delivery But Limited Transduction Capacity of Commonly Used Adeno-Associated Viral Serotypes in Xenotransplanted Human Skin.

PubMed

Jakobsen, Maria; Askou, Anne Louise; Stenderup, Karin; Rosada, Cecilia; Dagnæs-Hansen, Frederik; Jensen, Thomas G; Corydon, Thomas J; Mikkelsen, Jacob Giehm; Aagaard, Lars

2015-08-01

Skin is an easily accessible organ, and therapeutic gene transfer to skin remains an attractive alternative for the treatment of skin diseases. Although we have previously documented potent lentiviral gene delivery to human skin, vectors based on adeno-associated virus (AAV) rank among the most promising gene delivery tools for in vivo purposes. Thus, we compared the potential usefulness of various serotypes of recombinant AAV vectors and lentiviral vectors for gene transfer to human skin in a xenotransplanted mouse model. Vector constructs encoding firefly luciferase were packaged in AAV capsids of serotype 1, 2, 5, 6, 8, and 9 and separately administered by intradermal injection in human skin transplants. For all serotypes, live bioimaging demonstrated low levels of transgene expression in the human skin graft, and firefly luciferase expression was observed primarily in neighboring tissue outside of the graft. In contrast, gene delivery by intradermally injected lentiviral vectors was efficient and led to extensive and persistent firefly luciferase expression within the human skin graft only. The study demonstrates the limited capacity of single-stranded AAV vectors of six commonly used serotypes for gene delivery to human skin in vivo.

Robust Lentiviral Gene Delivery But Limited Transduction Capacity of Commonly Used Adeno-Associated Viral Serotypes in Xenotransplanted Human Skin

PubMed Central

Jakobsen, Maria; Askou, Anne Louise; Stenderup, Karin; Rosada, Cecilia; Dagnæs-Hansen, Frederik; Jensen, Thomas G.; Corydon, Thomas J.; Mikkelsen, Jacob Giehm; Aagaard, Lars

2015-01-01

Skin is an easily accessible organ, and therapeutic gene transfer to skin remains an attractive alternative for the treatment of skin diseases. Although we have previously documented potent lentiviral gene delivery to human skin, vectors based on adeno-associated virus (AAV) rank among the most promising gene delivery tools for in vivo purposes. Thus, we compared the potential usefulness of various serotypes of recombinant AAV vectors and lentiviral vectors for gene transfer to human skin in a xenotransplanted mouse model. Vector constructs encoding firefly luciferase were packaged in AAV capsids of serotype 1, 2, 5, 6, 8, and 9 and separately administered by intradermal injection in human skin transplants. For all serotypes, live bioimaging demonstrated low levels of transgene expression in the human skin graft, and firefly luciferase expression was observed primarily in neighboring tissue outside of the graft. In contrast, gene delivery by intradermally injected lentiviral vectors was efficient and led to extensive and persistent firefly luciferase expression within the human skin graft only. The study demonstrates the limited capacity of single-stranded AAV vectors of six commonly used serotypes for gene delivery to human skin in vivo. PMID:26204415

Rural and remote care

PubMed Central

Marciniuk, Darcy

2016-01-01

The challenges of providing quality respiratory care to persons living in rural or remote communities can be daunting. These populations are often vulnerable in terms of both health status and access to care, highlighting the need for innovation in service delivery. The rapidly expanding options available using telehealthcare technologies have the capacity to allow patients in rural and remote communities to connect with providers at distant sites and to facilitate the provision of diagnostic, monitoring, and therapeutic services. Successful implementation of telehealthcare programs in rural and remote settings is, however, contingent upon accounting for key technical, organizational, social, and legal considerations at the individual, community, and system levels. This review article discusses five types of telehealthcare delivery that can facilitate respiratory care for residents of rural or remote communities: remote monitoring (including wearable and ambient systems; remote consultations (between providers and between patients and providers), remote pulmonary rehabilitation, telepharmacy, and remote sleep monitoring. Current and future challenges related to telehealthcare are discussed. PMID:26902542

Homing of mesenchymal stem cells: mechanistic or stochastic? Implications for targeted delivery in arthritis.

PubMed

Eseonu, Onyedikachi I; De Bari, Cosimo

2015-02-01

Mesenchymal stem cells (MSCs) are multipotent cells with the capacity to undergo chondrogenic differentiation. Systemically administered MSCs have been shown to preferentially accumulate at sites of tissue damage and inflammation, thus MSC-based therapy holds great promise for the treatment of inflammatory diseases such as RA. Modulation of MSC homing may allow targeted delivery of systemically administered MSCs to damaged articular cartilage, where they can suppress immune-mediated cartilage destruction and contribute to cartilage repair via a combination of chondrogenic differentiation and paracrine stimulation of intrinsic residual repair. To harness the potential of MSC homing, a thorough understanding of the mechanism is key. This review discusses current knowledge of the mechanism of MSC homing to injured/inflamed tissue and its implications for targeted MSC-based therapy in arthritis. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A novel delivery system of doxorubicin with high load and pH-responsive release from the nanoparticles of poly (α,β-aspartic acid) derivative.

PubMed

Wang, Xiaojuan; Wu, Guolin; Lu, Caicai; Zhao, Weipeng; Wang, Yinong; Fan, Yunge; Gao, Hui; Ma, Jianbiao

2012-08-30

A poly (amino acid)-based amphiphilic copolymer was utilized to fabricate a better micellar drug delivery system (DDS) with improved compatibility and sustained release of doxorubicin (DOX). First, poly (ethylene glycol) monomethyl ether (mPEG) and DOX were conjugated onto polyasparihyazide (PAHy), prepared by hydrazinolysis of the poly (succinimide) (PSI), to afford an amphiphilic polymer [PEG-hyd-P (AHy-hyd-DOX)] with acid-liable hydrazone bonds. The DOX, chemically conjugated to the PAHy, was designed to supply hydrophobic segments. PEGs were also grafted to the polymer via hydrazone bonds to supply hydrophiphilic segments and prolong its lifetime in blood circulation. Free DOX molecules could be entrapped into the nanoparticles fabricated by such an amphiphilic polymer (PEG-hyd-P (AHy-hyd-DOX)), via hydrophobic interaction and π-π stacking between the conjugated and free DOX molecules to obtain a pH responsive drug delivery system with high DOX loaded. The drug loading capacity, drug release behavior, and morphology of the micelles were investigated. The biological activity of micelles was evaluated in vitro. The drug loading capacity was intensively augmented by adjusting the feed ratio, and the maximum loading capacity was as high as 38%. Besides, the DOX-loaded system exhibited pH-dependent drug release profiles in vitro. The cumulative release of DOX was much faster at pH 5.0 than that at pH 7.4. The DOX-loaded system kept highly antitumor activity for a long time, compared with free DOX. This easy-prepared DDS, with features of biocompatibility, biodegradability, high drug loading capacity and pH-responsiveness, was a promising controlled release delivery system for DOX. Copyright © 2012 Elsevier B.V. All rights reserved.

Heparin Microparticle Effects on Presentation and Bioactivity of Bone Morphogenetic Protein-2

PubMed Central

Hettiaratchi, Marian H.; Miller, Tobias; Temenoff, Johnna S.; Guldberg, Robert E.; McDevitt, Todd C.

2014-01-01

Biomaterials capable of providing localized and sustained presentation of bioactive proteins are critical for effective therapeutic growth factor delivery. However, current biomaterial delivery vehicles commonly suffer from limitations that can result in low retention of growth factors at the site of interest or adversely affect growth factor bioactivity. Heparin, a highly sulfated glycosaminoglycan, is an attractive growth factor delivery vehicle due to its ability to reversibly bind positively charged proteins, provide sustained delivery, and maintain protein bioactivity. This study describes the fabrication and characterization of heparin methacrylamide (HMAm) microparticles for recombinant growth factor delivery. HMAm microparticles were shown to efficiently bind several heparin-binding growth factors (e.g. bone morphogenetic protein-2 (BMP-2), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (FGF-2)), including a wide range of BMP-2 concentrations that exceeds the maximum binding capacity of other common growth factor delivery vehicles, such as gelatin. BMP-2 bioactivity was assessed on the basis of alkaline phosphatase (ALP) activity induced in skeletal myoblasts (C2C12). Microparticles loaded with BMP-2 stimulated comparable C2C12 ALP activity to soluble BMP-2 treatment, indicating that BMP-2-loaded microparticles retain bioactivity and potently elicit a functional cell response. In summary, our results suggest that heparin microparticles stably retain large amounts of bioactive BMP-2 for prolonged periods of time, and that presentation of BMP-2 via heparin microparticles can elicit cell responses comparable to soluble BMP-2 treatment. Consequently, heparin microparticles present an effective method of delivering and spatially retaining growth factors that could be used in a variety of systems to enable directed induction of cell fates and tissue regeneration. PMID:24881028

Potentiation of cGMP signaling increases oxygen delivery and oxidative metabolism in contracting skeletal muscle of older but not young humans

PubMed Central

Nyberg, Michael; Piil, Peter; Egelund, Jon; Sprague, Randy S; Mortensen, Stefan P; Hellsten, Ylva

2015-01-01

Aging is associated with progressive loss of cardiovascular and skeletal muscle function. The impairment in physical capacity with advancing age could be related to an insufficient peripheral O2 delivery to the exercising muscles. Furthermore, the mechanisms underlying an impaired blood flow regulation remain unresolved. Cyclic guanosine monophosphate (cGMP) is one of the main second messengers that mediate smooth muscle vasodilation and alterations in cGMP signaling could, therefore, be one mechanism by which skeletal muscle perfusion is impaired with advancing age. The current study aimed to evaluate the effect of inhibiting the main enzyme involved in cGMP degradation, phosphodiesterase 5 (PDE5), on blood flow and O2 delivery in contracting skeletal muscle of young and older humans. A group of young (23 ± 1 years) and a group of older (72 ± 2 years) male human subjects performed submaximal knee-extensor exercise in a control setting and following intake of the highly selective PDE5 inhibitor sildenafil. Sildenafil increased leg O2 delivery (6–9%) and leg O2 uptake (10–12%) at all three exercise intensities in older but not young subjects. The increase in leg O2 delivery with sildenafil in the older subjects correlated with the increase in leg O2 uptake (r2 = 0.843). These findings suggest an insufficient O2 delivery to the contracting skeletal muscle of aged individuals and that reduced cGMP availability is a novel mechanism underlying impaired skeletal muscle perfusion with advancing age. PMID:26272735

Exploiting Domain Knowledge to Forecast Heating Oil Consumption

NASA Astrophysics Data System (ADS)

Corliss, George F.; Sakauchi, Tsuginosuke; Vitullo, Steven R.; Brown, Ronald H.

2011-11-01

The GasDay laboratory at Marquette University provides forecasts of energy consumption. One such service is the Heating Oil Forecaster, a service for a heating oil or propane delivery company. Accurate forecasts can help reduce the number of trucks and drivers while providing efficient inventory management by stretching the time between deliveries. Accurate forecasts help retain valuable customers. If a customer runs out of fuel, the delivery service incurs costs for an emergency delivery and often a service call. Further, the customer probably changes providers. The basic modeling is simple: Fit delivery amounts sk to cumulative Heating Degree Days (HDDk = Σmax(0,60 °F—daily average temperature)), with wind adjustment, for each delivery period: sk≈ŝk = β0+β1HDDk. For the first few deliveries, there is not enough data to provide a reliable estimate K = 1/β1 so we use Bayesian techniques with priors constructed from historical data. A fresh model is trained for each customer with each delivery, producing daily consumption forecasts using actual and forecast weather until the next delivery. In practice, a delivery may not fill the oil tank if the delivery truck runs out of oil or the automatic shut-off activates prematurely. Special outlier detection and recovery based on domain knowledge addresses this and other special cases. The error at each delivery is the difference between that delivery and the aggregate of daily forecasts using actual weather since the preceding delivery. Out-of-sample testing yields MAPE = 21.2% and an average error of 6.0% of tank capacity for Company A. The MAPE and an average error as a percentage of tank capacity for Company B are 31.5 % and 6.6 %, respectively. One heating oil delivery company who uses this forecasting service [1] reported instances of a customer running out of oil reduced from about 250 in 50,000 deliveries per year before contracting for our service to about 10 with our service. They delivered slightly more oil with 20 % fewer trucks and drivers, citing 250,000 annual savings in operational costs.

Investing in nursing research in practice settings: a blueprint for building capacity.

PubMed

Jeffs, Lianne; Smith, Orla; Beswick, Susan; Maoine, Maria; Ferris, Ella

2013-12-01

Engaging clinical nurses in practice-based research is a cornerstone of professional nursing practice and a critical element in the delivery of high-quality patient care. Practising staff nurses are well suited to identify the phenomena and issues that are clinically relevant and appropriate for research. In response to the need to invest in and build capacity in nursing research, hospitals have developed creative approaches to spark interest in nursing research and to equip clinical nurses with research competencies. This paper outlines a Canadian hospital's efforts to build research capacity as a key strategy to foster efficacious, safe and cost-effective patient care practices. Within a multi-pronged framework, several strategies are described that collectively resulted in enhanced research and knowledge translation productivity aimed at improving the delivery of safe and high-quality patient care.

Developing Institutional Capacity for Reproductive Health in Humanitarian Settings: A Descriptive Study

PubMed Central

Tran, Nguyen-Toan; Dawson, Angela; Meyers, Janet; Krause, Sandra; Hickling, Carina

2015-01-01

Introduction Institutions play a central role in advancing the field of reproductive health in humanitarian settings (RHHS), yet little is known about organizational capacity to deliver RHHS and how this has developed over the past decade. This study aimed to document the current institutional experiences and capacities related to RHHS. Materials and Methods Descriptive study using an online questionnaire tool. Results Respondents represented 82 institutions from 48 countries, of which two-thirds originated from low-and middle-income countries. RHHS work was found not to be restricted to humanitarian agencies (25%), but was also embraced by development organizations (25%) and institutions with dual humanitarian and development mandates (50%). Agencies reported working with refugees (81%), internally-displaced (87%) and stateless persons (20%), in camp-based settings (78%), and in urban (83%) and rural settings (78%). Sixty-eight percent of represented institutions indicated having an RHHS-related policy, 79% an accountability mechanism including humanitarian work, and 90% formal partnerships with other institutions. Seventy-three percent reported routinely appointing RH focal points to ensure coordination of RHHS implementation. There was reported progress in RHHS-related disaster risk reduction (DRR), emergency management and coordination, delivery of the Minimum Initial Services Package (MISP) for RH, comprehensive RH services in post-crisis/recovery situations, gender mainstreaming, and community-based programming. Other reported institutional areas of work included capacity development, program delivery, advocacy/policy work, followed by research and donor activities. Except for abortion-related services, respondents cited improved efforts in advocacy, capacity development and technical support in their institutions for RHHS to address clinical services, including maternal and newborn health, sexual violence prevention and response, HIV prevention, management of sexually-transmitted infections, adolescent RH, and family planning. Approximately half of participants reported that their institutions had experienced an increase in dedicated budget and staff for RHHS, a fifth no change, and 1 in 10 a decrease. The Interagency RH Kits were reportedly the most commonly used supplies to support RHHS implementation. Conclusion The results suggest overall growth in institutional capacity in RHHS over the past decade, indicating that the field has matured and expanded from crisis response to include RHHS into DRR and other elements of the emergency management cycle. It is critical to consolidate the progress to date, address gaps, and sustain momentum. PMID:26331474

Nanoscale Delivery Systems: Actual and Potential Applications in the Natural Products Industry.

PubMed

Simona, Antal Diana; Florina, Ardelean; Rodica, Chis Aimee; Evelyne, Ollivier; Maria-Corina, Serban

2017-01-01

Compounds and extracts derived from natural sources continue to stand in the spotlight of drug design owing to their versatile interaction with enzymes, receptors and metabolic pathways. Nanomedicine offers an operative tool for the efficient delivery of natural products, in terms of increased bioavailability, targeting, and controlled release while protecting active constituents against physico-chemical alterations. The interest of the scientific community in the field of nanosized delivery of natural compounds is demonstrated by the exponential growth of the publications in this field. Beyond the presentation of successful examples of nanoscale delivery systems containing natural products, the scope of this review is to point out the yet underexplored capacities of this field with relevance for the pharmaceutical and nutraceutical market. Departing from a short presentation of plant-derived natural products and strategies to obtain nanoformulations, the current work discusses nanoparticulate drug delivery systems targeting diseases of various organs and systems: skin, central nervous system, skeletal tissue, cardiovascular apparatus, and diabetes. While notable progress has been achieved in the preparation of nanomedicines containing selected dietary polyphenols, works dealing with crude extracts or standardized fractions are much less frequent. In fact, most of the plants with solidly documented therapeutic properties and registered in pharmacopoeias still wait to benefit from advances in the field of nanotechnology. At least for some of them, adequate nanoformulation shall contribute to their removal from the group of dietary supplements and pharmaceutical preparations with suboptimal bioavailability and efficacy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Self-Assembly of pH-Responsive Microspheres for Intestinal Delivery of Diverse Lipophilic Therapeutics.

PubMed

Zhou, Xing; Zhao, Yang; Chen, Siyu; Han, Songling; Xu, Xiaoqiu; Guo, Jiawei; Liu, Mengyu; Che, Ling; Li, Xiaohui; Zhang, Jianxiang

2016-08-08

Targeted delivery of therapeutics to the intestine is preferred for the management of many diseases due to its diverse advantages. Currently, there are still challenges in creating cost-effective and translational pH-responsive microspheres for intestinal delivery of various hydrophobic drugs. Herein we report a multiple noncovalent interactions-mediated assembly strategy in which carboxyl-bearing compounds (CBCs) are guest molecules, while poly(N-isopropylacrylamide) (PNIPAm) serves as a host polymer. Formation of microparticles and therapeutic packaging can be achieved simultaneously by this assembly approach, leading to well-shaped microspheres with extremely higher drug loading capacity as compared to microspheres based on two FDA-approved materials of poly(d,l-lactide-co-glycolide) (PLGA) and an enteric coating polymer EudragitS 100 (S100). Also, carboxyl-deficient hydrophobic drugs can be effectively entrapped. These assembled microspheres, with excellent reconstitution capability as well as desirable scalability, could selectively release drug molecules under intestinal conditions. By significantly enhancing drug dissolution/release in the intestine, these pH-responsive assemblies may notably improve the oral bioavailability of loaded therapeutics. Moreover, the assembled microspheres possessed superior therapeutic performance in rodent models of inflammation and tumor over the control microspheres derived from PLGA and S100. Therapy with newly developed microspheres did not cause undesirable side effects. Furthermore, in vivo evaluation in mice revealed the carrier material PNIPAm was safe for oral delivery at doses as high as 10 g/kg. Collectively, our findings demonstrated that this type of pH-responsive microsphere may function as superior and translational intestine-directed delivery systems for a diverse array of therapeutics.

Inspired by nonenveloped viruses escaping from endo-lysosomes: a pH-sensitive polyurethane micelle for effective intracellular trafficking

NASA Astrophysics Data System (ADS)

Song, Nijia; Zhou, Lijuan; Li, Jiehua; Pan, Zhicheng; He, Xueling; Tan, Hong; Wan, Xinyuan; Li, Jianshu; Ran, Rong; Fu, Qiang

2016-03-01

A multifunctional drug delivery system (DDS) for cancer therapy still faces great challenges due to multiple physiological barriers encountered in vivo. To increase the efficacy of current cancer treatment a new anticancer DDS mimicking the response of nonenveloped viruses, triggered by acidic pH to escape endo-lysosomes, is developed. Such a smart DDS is self-assembled from biodegradable pH-sensitive polyurethane containing hydrazone bonds in the backbone, named pHPM. The pHPM exhibits excellent micellization characteristics and high loading capacity for hydrophobic chemotherapeutic drugs. The responses of the pHPM in acidic media, undergoing charge conversion and hydrophobic core exposure, resulting from the detachment of the hydrophilic polyethylene glycol (PEG) shell, are similar to the behavior of a nonenveloped virus when trapped in acidic endo-lysosomes. Moreover, the degradation mechanism was verified by gel permeation chromatography (GPC). The endo-lysosomal membrane rupture induced by these transformed micelles is clearly observed by transmission electron microscopy. Consequently, excellent antitumor activity is confirmed both in vitro and in vivo. The results verify that the pHPM could be a promising new drug delivery tool for the treatment of cancer and other diseases.A multifunctional drug delivery system (DDS) for cancer therapy still faces great challenges due to multiple physiological barriers encountered in vivo. To increase the efficacy of current cancer treatment a new anticancer DDS mimicking the response of nonenveloped viruses, triggered by acidic pH to escape endo-lysosomes, is developed. Such a smart DDS is self-assembled from biodegradable pH-sensitive polyurethane containing hydrazone bonds in the backbone, named pHPM. The pHPM exhibits excellent micellization characteristics and high loading capacity for hydrophobic chemotherapeutic drugs. The responses of the pHPM in acidic media, undergoing charge conversion and hydrophobic core exposure, resulting from the detachment of the hydrophilic polyethylene glycol (PEG) shell, are similar to the behavior of a nonenveloped virus when trapped in acidic endo-lysosomes. Moreover, the degradation mechanism was verified by gel permeation chromatography (GPC). The endo-lysosomal membrane rupture induced by these transformed micelles is clearly observed by transmission electron microscopy. Consequently, excellent antitumor activity is confirmed both in vitro and in vivo. The results verify that the pHPM could be a promising new drug delivery tool for the treatment of cancer and other diseases. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr00859c

Controlled drug delivery through a novel PEG hydrogel encapsulated silica aerogel system.

PubMed

Giray, Seda; Bal, Tuğba; Kartal, Ayse M; Kızılel, Seda; Erkey, Can

2012-05-01

A novel composite material consisting of a silica aerogel core coated by a poly(ethylene) glycol (PEG) hydrogel was developed. The potential of this novel composite as a drug delivery system was tested with ketoprofen as a model drug due to its solubility in supercritical carbon dioxide. The results indicated that both drug loading capacity and drug release profiles could be tuned by changing hydrophobicity of aerogels, and that drug loading capacity increased with decreased hydrophobicity, while slower release rates were achieved with increased hydrophobicity. Furthermore, higher concentration of PEG diacrylate in the prepolymer solution of the hydrogel coating delayed the release of the drug which can be attributed to the lower permeability at higher PEG diacrylate concentrations. The novel composite developed in this study can be easily implemented to achieve the controlled delivery of various drugs and/or proteins for specific applications. Copyright © 2012 Wiley Periodicals, Inc.

Reflections on CD-ROM: Bridging the Gap between Technology and Purpose.

ERIC Educational Resources Information Center

Saviers, Shannon Smith

1987-01-01

Provides a technological overview of CD-ROM (Compact Disc-Read Only Memory), an optically-based medium for data storage offering large storage capacity, computer-based delivery system, read-only medium, and economic mass production. CD-ROM database attributes appropriate for information delivery are also reviewed, including large database size,…

Platelet-Rich Plasma in Bone Regeneration: Engineering the Delivery for Improved Clinical Efficacy

PubMed Central

Rodriguez, Isaac A.; Growney Kalaf, Emily A.; Bowlin, Gary L.; Sell, Scott A.

2014-01-01

Human bone is a tissue with a fairly remarkable inherent capacity for regeneration; however, this regenerative capacity has its limitations, and defects larger than a critical size lack the ability to spontaneously heal. As such, the development and clinical translation of effective bone regeneration modalities are paramount. One regenerative medicine approach that is beginning to gain momentum in the clinical setting is the use of platelet-rich plasma (PRP). PRP therapy is essentially a method for concentrating platelets and their intrinsic growth factors to stimulate and accelerate a healing response. While PRP has shown some efficacy in both in vitro and in vivo scenarios, to date its use and delivery have not been optimized for bone regeneration. Issues remain with the effective delivery of the platelet-derived growth factors to a localized site of injury, the activation and temporal release of the growth factors, and the rate of growth factor clearance. This review will briefly describe the physiological principles behind PRP use and then discuss how engineering its method of delivery may ultimately impact its ability to successfully translate to widespread clinical use. PMID:25050347

From nose to brain: understanding transport capacity and transport rate of drugs.

PubMed

Wu, Hongbing; Hu, Kaili; Jiang, Xinguo

2008-10-01

The unique relationship between nasal cavity and cranial cavity tissues in anatomy and physiology makes intranasal delivery to the brain feasible. An intranasal delivery provides some drugs with short channels to bypass the blood-brain barrier (BBB), especially for those with fairly low brain concentrations after a routine delivery, thus greatly enhancing the therapeutic effect on brain diseases. In the past two decades, a good number of encouraging outcomes have been reported in the treatment of diseases of the brain or central nervous system (CNS) through nasal administration. In spite of the significant merit of bypassing the BBB, direct nose-to-brain delivery still bears the problems of low efficiency and volume for capacity due to the limited volume of the nasal cavity, the small area ratio of olfactory mucosa to nasal mucosa and the limitations of low dose and short retention time of drug absorption. It is crucial that selective distribution and retention time of drugs or preparations on olfactory mucosa should be enhanced so as to increase the direct delivery efficiency. In this article, we first briefly review the nose-to-brain transport pathways, before detailing the impacts on them, followed by a comprehensive summary of effective methods, including formulation modification, agglutinant-mediated transport and a brain-homing, peptide-mediated delivery based on phage display screening technique, with a view to providing a theoretic reference for elevating the therapeutic effects on brain diseases.

Discovering Entrepreneurship: An Exploration of a Tripartite Approach to Developing Entrepreneurial Capacities

ERIC Educational Resources Information Center

Collins, Lorna A.; Smith, Alison J.; Hannon, Paul D.

2006-01-01

Purpose: To describe an exploration in the use of synergistic learning methods in the delivery of an innovative pilot programme designed to teach entrepreneurship capacities. The programme took a tripartite approach involving nascent entrepreneurs, existing entrepreneurs and facilitators using an action research and action learning approach.…

A flexible solution for the next generation EPON with hybrid bidirectional 1Gbps and 10Gbps

NASA Astrophysics Data System (ADS)

Zhang, Weixun; Qiao, Yaojun; Li, Hui; Ji, Yuefeng

2007-11-01

Ethernet PON (EPON) has been proved to be a successful technology among all the standardized PON systems [1, 2], in terms of its cost-effective and large bandwidth virtue. And EPON has become a network of a choice for subscriber oriented digital service delivery, taking over the market previously dominated by DSL. However, with the development of advanced video services, the bandwidth capacity of current EPON seems to be not well suited for the future large deployment of triple-play services. Many researches are now taken about the Next Generation EPON; and the recent 10G EPON system standardization effort in the IEEE [3] results a lot of interest in the evolution of current PON systems towards high data rate system capable of providing a future-proof platform for delivery of personalized triple-play services. In this paper, a novel architecture of TDM-based 10GE-PON system is proposed. It combines the GE-PON and 10GE-PON systems, and provides symmetric 1Gbps/10Gbps or asymmetric access simultaneously. According to the results of the simulation on the system throughput and latency performance, the system is verified to be one solution and an important step from 1Gbit/s to 10Gbit/s for the Next Generation EPON.

Light-stimulated cargo release from a core–shell structured nanocomposite for site-specific delivery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cai, Yun; Ling, Li; Li, Xiaofang

This paper reported a core–shell structured site-specific delivery system with a light switch triggered by low energy light (λ=510 nm). Its core was composed of supermagnetic Fe{sub 3}O{sub 4} nanoparticles for magnetic guiding and targeting. Its outer shell consisted of mesoporous silica molecular sieve MCM-41 which offered highly ordered hexagonal tunnels for cargo capacity. A light switch N1-(4aH-cyclopenta[1,2-b:5,4-b′]dipyridin-5(5aH)-ylidene)benzene-1, 4-diamine (CBD) was covalently grafted into these hexagonal tunnels, serving as light stimuli acceptor with loading content of 1.1 μM/g. This composite was fully characterized and confirmed by SEM, TEM, XRD patterns, N{sub 2} adsorption/desorption, thermogravimetric analysis, IR, UV–vis absorption and emissionmore » spectra. Experimental data suggested that this composite had a core as wide as 150 nm and could be magnetically guided to specific sites. Its hexagonal tunnels were as long as 180 nm. Upon light stimuli of “on” and “off” states, controllable release was observed with short release time of ~900 s (90% capacity). - Graphical abstract: A core–shell structured site-specific delivery system with a light switch triggered by yellow light was constructed. Controllable release was observed with short release time of ~900 s (90% capacity). - Highlights: • A core–shell structured site-specific delivery system was constructed. • It consisted of Fe{sub 3}O{sub 4} core and MCM-41 shell grafted with light switch. • This delivery system was triggered by low energy light. • Controllable release was observed with short release time of ~900 s.« less

Exploiting the unique regenerative capacity of the liver to underpin cell and gene therapy strategies for genetic and acquired liver disease.

PubMed

Logan, Grant J; de Alencastro, Gustavo; Alexander, Ian E; Yeoh, George C

2014-11-01

The number of genetic or acquired diseases of the liver treatable by organ transplantation is ever-increasing as transplantation techniques improve placing additional demands on an already limited organ supply. While cell and gene therapies are distinctly different modalities, they offer a synergistic alternative to organ transplant due to distinct architectural and physiological properties of the liver. The hepatic blood supply and fenestrated endothelial system affords relatively facile accessibility for cell and/or gene delivery. More importantly, however, the remarkable capacity of hepatocytes to proliferate and repopulate the liver creates opportunities for new treatments based on emerging technologies. This review will summarise current understanding of liver regeneration, describe clinical and experimental cell and gene therapeutic modalities and discuss critical challenges to translate these new technologies to wider clinical utility. This article is part of a Directed Issue entitled: "Regenerative Medicine: the challenge of translation". Copyright © 2014 Elsevier Ltd. All rights reserved.

[A day in the busy obstetric unit from the anesthesiologist point of view, experience at the Cleveland clinic; Cleveland, Ohio].

PubMed

Ootaki, Chiyo; Barsoum, Sabri

2009-10-01

Cleveland Clinic Labor and Delivery Unit is a syntactical delivery facility and comprised of 16 delivery rooms, 3 operating rooms, 3 triage rooms, and 1 recovery room that has a capacity of 6 beds, 43 postpartum rooms, 2 nurseries, and 1 neonatal intensive care unit (NICU). Cleveland Clinic Labor and Delivery Unit (LDU) had 3,691 delivery cases in 2007. The ratio of neuraxial analgesia (NA) during labor is 84.2% (2,348/ 2,787), using epidural anesthesia or combined spinalepidural anesthesia (CSEA). This article introduces the obstetrical (OB) anesthesia practice at the Cleveland Clinic and our novel anesthetic regime as typical of one typical busy day.

Institutional capacity to provide psychosocial oncology support services: A report from the Association of Oncology Social Work.

PubMed

Zebrack, Brad; Kayser, Karen; Padgett, Lynne; Sundstrom, Laura; Jobin, Chad; Nelson, Krista; Fineberg, Iris C

2016-06-15

This study reports cancer-treating institutions' capacity to deliver comprehensive psychosocial support services. Oncology care providers at 60 cancer-treating institutions completed surveys assessing the capacity of their institutions to provide psychosocial care. Capacity was assessed with the Cancer Psychosocial Care Matrix (CPCM) from the National Cancer Institute (NCI). Scores represented individuals' perceptions of their cancer program's performance with respect to 10 fundamental elements of psychosocial care. Among 2134 respondents, 62% reported a mid-level capacity for ≥5 of 10 CPCM items. In comparison with other types of cancer programs (eg, NCI-designated, academic, or comprehensive centers), providers at community cancer programs reported a significantly greater capacity with respect to patient-provider communication, psychosocial needs assessment, and continuity in the delivery of psychosocial care over time. Nurses and primary medical providers reported a significantly lower capacity for linking patients and families with needed psychosocial services within their respective cancer programs. They also reported a significantly higher capacity for conducting follow-up, re-evaluations, and adjustments of psychosocial treatment plans. Cancer programs are performing moderately well in terms of communicating to patients the importance of psychosocial care, identifying patient psychosocial needs, and referring patients and families to psychosocial services. They are doing less well with respect to the provision of that care over time. Findings suggest that gaps in psychosocial service capacity are a function of patient, provider, and system characteristics. These results may be useful in formulating strategies to enhance psychosocial care delivery. Cancer 2016;122:1937-45. © 2016 American Cancer Society. © 2016 American Cancer Society.

NIR and MR imaging supported hydrogel based delivery system for anti-TNF alpha probiotic therapy of IBD

NASA Astrophysics Data System (ADS)

Janjic, Jelena M.; Berlec, Ales; Bagia, Christina; Liu, Lu S.; Jeric, Irenej; Gach, Michael; Janjic, Bratislav M.; Strukelj, Borut

2016-03-01

Current treatment of inflammatory bowel disease (IBD) is largely symptomatic and consists of anti-inflammatory agents, immune-suppressives or antibiotics, whereby local luminal action is preferred to minimize systemic side-effects. Recently, anti-TNFα therapy has shown considerable success and is now being routinely used. Here we present a novel approach of using perfluorocarbon (PFC) nanoemulsion containing hydrogels (nanoemulgels) as imaging supported delivery systems for anti-TNF alpha probiotic delivery in IBD. To further facilitate image-guided therapy a food-grade lactic acid bacterium Lactococcus lactis capable of TNFα-binding was engineered to incorporate infrared fluorescent protein (IRFP). This modified bacteria was then incorporated into novel PFC nanoemulgels. The nanoemulgels presented here are designed to deliver locally anti-TNFα probiotic in the lower colon and rectum and provide dual imaging signature of gel delivery (MRI) across the rectum and lower colon and bacteria release (NIR). NIR imaging data in vitro demonstrates high IRFP expressing and TNFα-binding bacteria loading in the hydrogel and complete release in 3 hours. Stability tests indicate that gels remain stable for at least 14 days showing no significant change in droplet size, zeta potential and pH. Flow cytometry analyses demonstrate the NIRF expressing bacteria L. lactis binds TNFα in vitro upon release from the gels. Magnetic resonance and near-infrared imaging in vitro demonstrates homogeneity of hydrogels and the imaging capacity of the overall formulation.

Characterization of glycol chitosan grafted with low molecular weight polyethylenimine as a gene carrier for human adipose-derived mesenchymal stem cells.

PubMed

Bae, Yoonhee; Lee, Young Hwa; Lee, Sunray; Han, Jin; Ko, Kyung Soo; Choi, Joon Sig

2016-11-20

Mesenchymal stem cells (MSCs) have a great capacity for self-renewal while still maintaining their multipotency, and can differentiate into a variety of cell types. The delivery of genes to a site of injury is a current and interesting field of gene therapy. In the present study, we describe a nonviral gene delivery carrier, glycol chitosan-methyl acrylate-polyethylenimine (GMP) polymer targeted towards human adipose-derived mesenchymal stem cells (AD-MSCs). Transfection efficiency, using luciferase (Luc) and a pDNA encoding enhanced green fluorescent protein (EGFP), along with cytotoxicity assays, were performed in human AD-MSCs. The results show that the transfection efficiency of the GMP polymer was similar to that of PEI25kD, and the cytotoxicity was lower. Moreover, human AD-MSCs were treated with the GMP polymer/pDNA polyplex and its cellular uptake and distribution were analyzed by flow cytometry and confocal microscopy. Furthermore, we performed endosomal escape analysis using LysoTracker Red, and found that the conjugated GMP polymer could escape from the endosome to the cytosol. Human AD-MSCs treated with the GMP polymer maintained their potential for osteogenic differentiation and phenotypic expression of human AD-MSCs based on flow cytometry analysis. The present study demonstrates that the GMP polymer can be used as a potential targeted-delivery carrier for effective gene delivery. Copyright © 2016 Elsevier Ltd. All rights reserved.

HBOC vasoactivity: interplay between nitric oxide scavenging and capacity to generate bioactive nitric oxide species.

PubMed

Cabrales, Pedro; Friedman, Joel M

2013-06-10

Despite many advances in blood substitute research, the development of materials that are effective in maintaining blood volume and oxygen delivery remains a priority for emergency care and trauma. Clinical trials on hemoglobin (Hb)-based oxygen carriers (HBOCs) have not provided information on the mechanism of toxicity, although all commercial formulations have safety concerns. Specifically, it is important to reconcile the different hypotheses of Hb toxicity, such as nitric oxide (NO) depletion and oxidative reactions, to provide a coherent molecular basis for designing a safe HBOC. HBOCs with different sizes often exhibit differences in the degree of HBOC-induced vasoactivity. This has been attributed to differences in the degree of NO scavenging and in the extent of Hb extravasation. Additionally, it is appears that Hb can undergo reactions that compensate for NO scavenging by generating bioactive forms of NO. Engineering modifications to enhance bioactive NO production can result in diminished oxygen delivery by virtue of increased oxygen affinity. This strategy can prevent the HBOC from fulfilling the intended goal on preserving oxygenation; however, the NO production effects will increase perfusion and oxygen transport. Hb modifications influence NO scavenging and the capacity of certain HBOCs to compensate for NO scavenging through nitrite-mediated reactions that generate bioactive NO. Based on the current understanding of these NO-related factors, possible synthetic strategies are presented that address how HBOC formulations can be prepared that: (i) effectively deliver oxygen, (ii) maintain tissue perfusion, and (iii) limit/reverse underlying inflammation within the vasculature.

Concepts in Gene Therapy for Cartilage Repair

PubMed Central

Steinert, Andre F.; Nöth, Ulrich; Tuan, Rocky S.

2009-01-01

Summary Once articular cartilage is injured, it has a very limited capacity for self-repair. Although current surgical therapeutic procedures to cartilage repair are clinically useful, they cannot restore a normal articular surface. Current research offers a growing number of bioactive reagents, including proteins and nucleic acids, that may be used to augment different aspects of the repair process. As these agents are difficult to administer effectively, gene transfer approaches are being developed to provide their sustained synthesis at sites of repair. To augment regeneration of articular cartilage, therapeutic genes can be delivered to the synovium, or directly to the cartilage lesion. Gene delivery to the cells of the synovial lining is generally considered more suitable for chondroprotective approaches, based on the expression of anti-inflammatory mediators. Gene transfer targeted to cartilage defects can be achieved by either direct vector administration to cells located at or surrounding the defects, or by transplantation of genetically modified chondrogenic cells into the defect. Several studies have shown that exogenous cDNAs encoding growth factors can be delivered locally to sites of cartilage damage, where they are expressed at therapeutically relevant levels. Furthermore, data is beginning to emerge indicating, that efficient delivery and expression of these genes is capable of influencing a repair response toward the synthesis of a more hyaline cartilage repair tissue in vivo. This review presents the current status of gene therapy for cartilage healing and highlights some of the remaining challenges. PMID:18313477

An innovation for improving maternal, newborn and child health (MNCH) service delivery in Jigawa State, northern Nigeria: a qualitative study of stakeholders' perceptions about clinical mentoring.

PubMed

Okereke, Ekechi; Tukur, Jamilu; Aminu, Amina; Butera, Jean; Mohammed, Bello; Tanko, Mustapha; Yisa, Ibrahim; Obonyo, Benson; Egboh, Mike

2015-02-15

An effective capacity building process for healthcare workers is required for the delivery of quality health care services. Work-based training can be applied for the capacity building of health care workers while causing minimum disruption to service delivery within health facilities. In 2012, clinical mentoring was introduced into the Jigawa State Health System through collaboration between the Jigawa State Ministry of Health and the Partnership for Transforming Health Systems Phase 2 (PATHS2). This study evaluates the perceptions of different stakeholders about clinical mentoring as a strategy for improving maternal, newborn and child health service delivery in Jigawa State, northern Nigeria. Interviews were conducted in February 2013 with different stakeholders within Jigawa State in Northern Nigeria. There were semi-structured interviews with 33 mentored health care workers as well as the health facility departmental heads for Obstetrics and Pediatrics in the selected clinical mentoring health facilities. In-depth interviews were also conducted with the clinical mentors and two senior government health officials working within the Jigawa State Ministry of Health. The qualitative data were audio-recorded; transcribed and thematically analysed. The study findings suggest that clinical mentoring improved service delivery within the clinical mentoring health facilities. Significant improvements in the professional capacity of mentored health workers were observed by clinical mentors, heads of departments and the mentored health workers. Best practices were introduced with the support of the clinical mentors such as appropriate baseline investigations for pediatric patients, the use of magnesium sulphate and misoprostol for the management of eclampsia and post-partum hemorrhage respectively. Government health officials indicate that clinical mentoring has led to more emphasis on the need for the provision of better quality health services. Stakeholders report that the introduction of clinical mentoring into the Jigawa State health system gave rise to an improved capacity of the mentored health care workers to deliver better quality maternal, newborn and child health services. It is anticipated that with a scale up of clinical mentoring, health outcomes will also significantly improve across northern Nigeria.

The role of NGOs' service delivery experience in developing relevant research agendas: experience and challenges among NGOs in Malawi.

PubMed

Gooding, Kate

2017-05-04

There has been growing interest in the contribution of non-governmental organisations (NGOs) to international health research. One strength that NGOs may bring to research involves the potential value of service delivery experience for indicating relevant research questions, namely through their involvement in service delivery, NGO staff may be aware of frontline knowledge gaps, allowing these staff to identify questions that lead to research with immediate relevance. However, there is little empirical evidence on research agendas within NGOs to assess whether their service delivery experience does lead to relevant research or conditions that affect this. This article examines the identification and selection of research questions within NGOs to explore the role of their service delivery experience in generating relevant research agendas. The article reports comparative case study research on four NGOs in Malawi, including two international and two Malawian organisations. Each NGO conducts research and undertakes service delivery and advocacy. Data collection included interviews, focus groups, observation and document review. Analysis involved thematic coding and use of diagrams. The case NGOs' experiences suggest that using service delivery to identify research questions does not always match NGOs' aims or capacities, and does not guarantee relevance. First, NGOs do not want to rely only on service delivery when developing research agendas; they consider other criteria and additional sources of ideas when selecting questions they see as relevant. Second, service delivery staff are not always well-placed to identify research topics; indeed, involvement in hectic, target-driven service delivery can hinder input to research agendas. Third, NGOs' ability to pursue questions inspired by service delivery depends on control over their research agendas; relationships with external actors and financial autonomy affect NGOs' capacity to undertake the research they see as relevant. Finally, the perceived relevance of research findings varies between audiences and depends on more than the research question. The findings suggest limits to the value and feasibility of a research agenda based on service delivery experience. Based on the analysis, the conclusion outlines strategies to support an effective role for NGOs' service delivery experience in development of research agendas.

An Overview of Practice Facilitation Programs in Canada: Current Perspectives and Future Directions

PubMed Central

Liddy, Clare; Laferriere, Dianne; Baskerville, Bruce; Dahrouge, Simone; Knox, Lyndee; Hogg, William

2013-01-01

Practice facilitation has proven to be effective in improving the quality of primary care. A practice facilitator is a health professional, usually external to the practice, who regularly visits the practice to provide support in change management that targets improvements in the delivery of care. Our environmental scan shows that several initiatives across Canada utilize practice facilitation as a quality improvement method; however, many are conducted in isolation as there is a lack of coordinated effort, knowledge translation and dissemination in this field across the country. We recommend that investments be made in capacity building, knowledge exchange and facilitator training, and that partnership building be considered a priority in this field. PMID:23968627

Analog and digital transport of RF channels over converged 5G wireless-optical networks

NASA Astrophysics Data System (ADS)

Binh, Le Nguyen

2016-02-01

Under the exponential increase demand by the emerging 5G wireless access networking and thus data-center based Internet, novel and economical transport of RF channels to and from wireless access systems. This paper presents the transport technologies of RF channels over the analog and digital domain so as to meet the demands of the transport capacity reaching multi-Tbps, in the followings: (i) The convergence of 5G broadband wireless and optical networks and its demands on capacity delivery and network structures; (ii) Analog optical technologies for delivery of both the information and RF carriers to and from multiple-input multiple-output (MIMO) antenna sites so as to control the beam steering of MIMO antenna in the mmW at either 28.6 GHz and 56.8 GHz RF carrier and delivery of channels of aggregate capacity reaching several Tbps; (ii) Transceiver employing advanced digital modulation formats and digital signal processing (DSP) so as to provide 100G and beyond transmission rate to meet the ultra-high capacity demands with flexible spectral grids, hence pay-on-demand services. The interplay between DSP-based and analog transport techniques is examined; (iii) Transport technologies for 5G cloud access networks and associate modulation and digital processing techniques for capacity efficiency; and (iv) Finally the integrated optic technologies with novel lasers, comb generators and simultaneous dual function photonic devices for both demultiplexing/multiplexing and modulation are proposed, hence a system on chip structure can be structured. Quantum dot lasers and matrixes of micro ring resonators are integrated on the same Si-on-Silica substrate are proposed and described.

Liposome-chaperoned cell-free synthesis for the design of proteoliposomes: Implications for therapeutic delivery.

PubMed

Lu, Mei; Zhao, Xiaoyun; Xing, Haonan; Xun, Zhe; Yang, Tianzhi; Cai, Cuifang; Wang, Dongkai; Ding, Pingtian

2018-04-03

Cell-free (CF) protein synthesis has emerged as a powerful technique platform for efficient protein production in vitro. Liposomes have been widely studied as therapeutic carriers due to their biocompatibility, biodegradability, low toxicity, flexible surface manipulation, easy preparation, and higher cargo encapsulation capability. However, rapid immune clearance, insufficient targeting capacity, and poor cytoplasmic delivery efficiency substantially restrict their clinical application. The incorporation of functional membrane proteins (MPs) or peptides allows the transfer of biological properties to liposomes and imparts them with improved circulation, increased targeting, and efficient intracellular delivery. Liposome-chaperoned CF synthesis enables production of proteoliposomes in one-step reaction, which not only substantially simplifies the production procedure but also keeps protein functionality intact. Building off these observations, proteoliposomes with integrated MPs represent an excellent candidate for therapeutic delivery. In this review, we describe recent advances in CF synthesis with emphasis on detailing key factors for improving CF expression efficiency. Furthermore, we provide insights into strategies for rational design of proteoliposomal nanodelivery systems via CF synthesis. Liposome-chaperoned CF synthesis has emerged as a powerful approach for the design of recombinant proteoliposomes in one-step reaction. The incorporation of bioactive MPs or peptides into liposomes via CF synthesis can facilitate the development of proteoliposomal nanodelivery systems with improved circulation, increased targeting, and enhanced cellular delivery capacity. Moreover, by adapting lessons learned from natural delivery vehicles, novel bio-inspired proteoliposomes with enhanced delivery properties could be produced in CF systems. In this review, we first give an overview of CF synthesis with focus on enhancing protein expression in liposome-chaperoned CF systems. Furthermore, we intend to provide insight into harnessing CF-synthesized proteoliposomes for efficient therapeutic delivery. Copyright © 2018. Published by Elsevier Ltd.

Efficient siRNA delivery system using carboxilated single-wall carbon nanotubes in cancer treatment.

PubMed

Neagoe, Ioana Berindan; Braicu, Cornelia; Matea, Cristian; Bele, Constantin; Florin, Graur; Gabriel, Katona; Veronica, Chedea; Irimie, Alexandru

2012-08-01

Several functionalized carbon nanotubes have been designed and tested for the purpose of nucleic acid delivery. In this study, the capacity of SWNTC-COOH for siRNA deliverey were investigated delivery in parallel with an efficient commercial system. Hep2G cells were reverse-transfected with 50 nM siRNA (p53 siRNA, TNF-alphasiRNA, VEGFsiRNA) using the siPORT NeoFX (Ambion) transfection agent in paralel with SWNTC-COOH, functionalised with siRNA. The highest level of gene inhibition was observed in the cases treated with p53 siRNA gene; in the case of transfection with siPort, the NeoFX value was 33.8%, while in the case of SWNTC-COOH as delivery system for p53 siRNA was 37.5%. The gene silencing capacity for VEGF was 53.7%, respectively for TNF-alpha 56.7% for siPORT NeoFX delivery systems versus 47.7% (VEGF) and 46.5% (TNF-alpha) for SWNTC-COOH delivery system. SWNTC-COOH we have been showed to have to be an efficient carrier system. The results from the inhibition of gene expresion for both transfection systems were confirmed at protein level. Overall, the lowest mRNA expression was confirmed at protein level, especially in the case of p53 siRNA and TNF-alpha siRNA transfection. Less efficient reduction protein expressions were observed in the case of VEGF siRNA, for both transfection systems at 24 h; only at 48 h, there was a statistically significant reduction of VEGF protein expression. SWCNT-COOH determined an efficient delivery of siRNA. SWNTC-COOH, combined with suitable tumor markers like p53 siRNA, TNFalpha siRNA or VEGF siRNA can be used for the efficient delivery of siRNA.

Lipid nanoparticles as drug/gene delivery systems to the retina.

PubMed

del Pozo-Rodríguez, Ana; Delgado, Diego; Gascón, Alicia R; Solinís, Maria Ángeles

2013-03-01

This review highlights the application of lipid nanoparticles (Solid Lipid Nanoparticles, Nanostructured Lipid Carriers, or Lipid Drug Conjugates) as effective drug/gene delivery systems for retinal diseases. Most drug products for ocular disease treatment are marketed as eye drop formulations but, due to ocular barriers, the drug concentration in the retina hardly ever turns out to be effective. Up to this date, several delivery systems have been designed to deliver drugs to the retina. Drug delivery strategies may be classified into 3 groups: noninvasive techniques, implants, and colloidal carriers. The best known systems for drug delivery to the posterior eye are intravitreal implants; in fact, some of them are being clinically used. However, their long-term accumulation might impact the patient's vision. On the contrary, colloidal drug delivery systems (microparticles, liposomes, or nanoparticles) can be easily administered in a liquid form. Nanoparticular systems diffuse rapidly and are better internalized in ocular tissues than microparticles. In comparison with liposomes, nanoparticles have a higher loading capacity and are more stable in biological fluids and during storage. In addition, their capacity to adhere to the ocular surface and interact with the endothelium makes these drug delivery systems interesting as new therapeutic tools in ophthalmology. Within the group of nanoparticles, those composed of lipids (Solid Lipid Nanoparticles, Nanostructred Lipid Carriers, and Lipid Drug Conjugates) are more biocompatible, easy to produce at large scale, and they may be autoclaved or sterilized. The present review summarizes scientific results that evidence the potential application of lipid nanoparticles as drug delivery systems for the retina and also as nonviral vectors in gene therapy of retina disorders, although much more effort is still needed before these lipidic systems could be available in the market.

Capacity Building for Online Education in a Dual Mode Higher Education Institution

ERIC Educational Resources Information Center

Kuboni, Olabisi

2013-01-01

This paper outlines the strategies employed by the Graduate Programmes Department of the University of the West Indies Open Campus to build capacity among academic staff to facilitate their transition to online teaching and learning. The strategies covered relate to course development and delivery, including activities that emerge at the interface…

Characterization of Nano Bamboo Charcoal Drug Delivery System for Eucommia ulmoides Extract and Its Anticancer Effect In vitro.

PubMed

Zeng, Zhaoyan; Li, Xiangzhou; Zhang, Sheng; Huang, Dan

2017-01-01

Nano bamboo charcoal is being widely used as sustained release carrier for chemicals for its high specific surface area, sound biocompatibility, and nontoxicity; however, there have been no reports on nano bamboo charcoal as sustained release carrier for traditional Chinese medicine (TCM). To study the effect of nano bamboo charcoal in absorbing and sustained releasing Eucommia ulmoides extract (EUE) and to verify the in vitro anticancer effect of the sustained release liquid, so as to provide a theoretical basis for the development and utilization of nano bamboo charcoal as TCM sustained-release preparation. The adsorption capacity for the nano bamboo charcoal on EUE was measured by Langmuir model, and the release experiment was carried out under intestinal fluid condition. Characteristic changes for the nano bamboo charcoal nano-drug delivery system with and without adsorption of E. ulmoides were evaluated by scanning electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, and specific surface area. In addition, the anticancer effect from this novel bamboo charcoal E. ulmoides delivery system was evaluated against a human colon cancer cell line (HCT116). It was found that nano bamboo charcoal exhibits good adsorption capacity (up to 462.96 mg/g at 37°C). The cumulative release rate for EUE from this nano bamboo charcoal delivery system was 70.67%, and specific surface area for the nano bamboo charcoal decreased from 820.32 m 2 /g to 443.80 m 2 /g after EUE was loaded. An in vitro anticancer study showed that the inhibition rate for E. ulmoides against HCT116 cancer cells was 23.07%, for this novel bamboo charcoal nano-drug delivery system. This study provides a novel strategy for the delivery of traditional Chinese medicine using bamboo charcoal nano-drug delivery system. The adsorption equilibrium was reached after 30 min of ultrasonic treatmentThe saturated adsorption capacity of Eucommia ulmoides extract by nano bamboo charcoal under ultrosonic condition was 462. 96 mg/gThe cumulative release rate of E. ulmoides extract from the nano bamboo charcoal delivery system in artificial intestinal juice was 70.67%The inhibition ratio of HCT116 cancer cells by sustained release liquid was 23.07%. Abbreviation used: EUE: Eucommia ulmoides extract.

Heterogeneous delivering capability promotes traffic efficiency in complex networks

NASA Astrophysics Data System (ADS)

Zhu, Yan-Bo; Guan, Xiang-Min; Zhang, Xue-Jun

2015-12-01

Traffic is one of the most fundamental dynamical processes in networked systems. With the homogeneous delivery capability of nodes, the global dynamic routing strategy proposed by Ling et al. [Phys. Rev. E81, 016113 (2010)] adequately uses the dynamic information during the process and thus it can reach a quite high network capacity. In this paper, based on the global dynamic routing strategy, we proposed a heterogeneous delivery allocation strategy of nodes on scale-free networks with consideration of nodes degree. It is found that the network capacity as well as some other indexes reflecting transportation efficiency are further improved. Our work may be useful for the design of more efficient routing strategies in communication or transportation systems.

TH-AB-BRB-04: Quality Assurance for Advanced Digital Linac Implementations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, V.

2016-06-15

Current state-of-the art digital C-arm medical linear accelerators are capable of delivering radiation treatments with high level of automation, which affords coordinated motions of gantry, couch, and multileaf collimator (MLC) with dose rate modulations. The new machine capacity has shown the potential to bring substantially improved radiation dosimetry and/or delivery efficiency to many challenging diseases. Combining an integrated beam orientation optimization algorithm with automated machine navigation, markedly improved dose conformity has been achieved using 4ρ therapy. Trajectory modulated radiation therapy (TMAT) can be used to deliver highly conformal dose to partial breast or to carve complex dose distribution for therapymore » involving extended volumes such as total marrow and total lymph node treatment. Dynamic electron arc radiotherapy (DEAR) not only overcomes the deficiencies of conventional electron therapy in dose conformity and homogeneity but also achieves so without patient-specific shields. The combination of MLC and couch tracking provides improved motion management of thoracic and abdominal tumors. A substantial body of work has been done in these technological advances for clinical translation. The proposed symposium will provide a timely review of these exciting opportunities. Learning Objectives: Recognize the potential of using digitally controlled linacs for clinically significant improvements in delivered dose distributions for various treatment sites. Identify existing approaches to treatment planning, optimization and delivery for treatment techniques utilizing the advanced functions of digital linacs and venues for further development and improvement. Understand methods for testing and validating delivery system performance. Identify tools available on current delivery systems for implementation and control for such treatments. Obtain the update in clinical applications, trials and regulatory approval. K. Sheng, NIH U19AI067769, NIH R43CA183390, NIH R01CA188300, Varian Medical Systems V. Yu, Varian Medical Systems, AAPM Summer Undergraduate Fellowship, NSF graduate fellowship S. Nill, Elekta AB. Cancer Research UK under Programme C33589/A19727, NIHR Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research.« less

TH-AB-BRB-00: Research Opportunities with Digital Linear Accelerators

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

2016-06-15

Current state-of-the art digital C-arm medical linear accelerators are capable of delivering radiation treatments with high level of automation, which affords coordinated motions of gantry, couch, and multileaf collimator (MLC) with dose rate modulations. The new machine capacity has shown the potential to bring substantially improved radiation dosimetry and/or delivery efficiency to many challenging diseases. Combining an integrated beam orientation optimization algorithm with automated machine navigation, markedly improved dose conformity has been achieved using 4ρ therapy. Trajectory modulated radiation therapy (TMAT) can be used to deliver highly conformal dose to partial breast or to carve complex dose distribution for therapymore » involving extended volumes such as total marrow and total lymph node treatment. Dynamic electron arc radiotherapy (DEAR) not only overcomes the deficiencies of conventional electron therapy in dose conformity and homogeneity but also achieves so without patient-specific shields. The combination of MLC and couch tracking provides improved motion management of thoracic and abdominal tumors. A substantial body of work has been done in these technological advances for clinical translation. The proposed symposium will provide a timely review of these exciting opportunities. Learning Objectives: Recognize the potential of using digitally controlled linacs for clinically significant improvements in delivered dose distributions for various treatment sites. Identify existing approaches to treatment planning, optimization and delivery for treatment techniques utilizing the advanced functions of digital linacs and venues for further development and improvement. Understand methods for testing and validating delivery system performance. Identify tools available on current delivery systems for implementation and control for such treatments. Obtain the update in clinical applications, trials and regulatory approval. K. Sheng, NIH U19AI067769, NIH R43CA183390, NIH R01CA188300, Varian Medical Systems V. Yu, Varian Medical Systems, AAPM Summer Undergraduate Fellowship, NSF graduate fellowship S. Nill, Elekta AB. Cancer Research UK under Programme C33589/A19727, NIHR Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research.« less

Composite HPMC and sodium alginate based buccal formulations for nicotine replacement therapy.

PubMed

Okeke, Obinna C; Boateng, Joshua S

2016-10-01

Smoking cessation is of current topical interest due to the significant negative health and economic impact in many countries. This study aimed to develop buccal films and wafers comprising HPMC and sodium alginate (SA) for potential use in nicotine replacement therapy via the buccal mucosa, as a cheap but effective alternative to currently used nicotine patch and chewing gum. The formulations were characterised using texture analyser (tensile and hardness, mucoadhesion), scanning electron microscopy, X-ray diffractometry, attenuated total reflection-Fourier transform infrared (ATR-FTIR), differential scanning calorimetry (DSC) and swelling capacity. Drug loaded films and wafers were characterised for content uniformity (HPLC) whilst the drug loaded wafers only were further characterised for in vitro drug dissolution. SA modified and improved the functional properties of HPMC at optimum ratio of HPMC: SA of 1.25: 0.75. Generally, both films and wafers (blank and drug loaded) were amorphous in nature which impacted on swelling and mucoadhesive performance. HPMC-SA composite wafers showed a porous internal morphology with higher mucoadhesion, swelling index and drug loading capacity compared to the HPMC-SA composite films which were non-porous. The study demonstrates the potential use of composite HPMC-SA wafers in the buccal delivery nicotine. Copyright © 2016 Elsevier B.V. All rights reserved.

Acoustically active liposome-nanobubble complexes for enhanced ultrasonic imaging and ultrasound-triggered drug delivery.

PubMed

Nguyen, An T; Wrenn, Steven P

2014-01-01

Ultrasound is well known as a safe, reliable imaging modality. A historical limitation of ultrasound, however, was its inability to resolve structures at length scales less than nominally 20 µm, which meant that classical ultrasound could not be used in applications such as echocardiography and angiogenesis where one requires the ability to image small blood vessels. The advent of ultrasound contrast agents, or microbubbles, removed this limitation and ushered in a new wave of enhanced ultrasound applications. In recent years, the microbubbles have been designed to achieve yet another application, namely ultrasound-triggered drug delivery. Ultrasound contrast agents are thus tantamount to 'theranostic' vehicles, meaning they can do both therapy (drug delivery) and imaging (diagnostics). The use of ultrasound contrast agents as drug delivery vehicles, however, is perhaps less than ideal when compared to traditional drug delivery vehicles (e.g., polymeric microcapsules and liposomes) which have greater drug carrying capacities. The drawback of the traditional drug delivery vehicles is that they are not naturally acoustically active and cannot be used for imaging. The notion of a theranostic vehicle is sufficiently intriguing that many attempts have been made in recent years to achieve a vehicle that combines the echogenicity of microbubbles with the drug carrying capacity of liposomes. The attempts can be classified into three categories, namely entrapping, tethering, and nesting. Of these, nesting is the newest-and perhaps the most promising. © 2014 Wiley Periodicals, Inc.

Nitrogen fluxes at the root-soil interface show a mismatch of nitrogen fertilizer supply and sugarcane root uptake capacity

NASA Astrophysics Data System (ADS)

Inselsbacher, Erich; Schmidt, Susanne; Näsholm, Torgny; Robinson, Nicole; Guillou, Stéphane; Vinall, Kerry; Lakshmanan, Prakash; Brackin, Richard

2016-04-01

Nitrogen (N) uptake by agricultural crops is a key constituent of the global N cycle, as N captured by roots has a markedly different fate than N remaining in the soil. Global evidence indicates that only approximately 50% of applied N fertilizer is captured by crops, and the remainder can cause pollution via runoff and gaseous emissions. This inefficiency is of global concern, and requires innovation based on improved understanding of which N forms are available for and ultimately taken up by crops. However, current soil analysis methods based on destructive soil sampling provide little insight into delivery and acquisition of N forms by roots. Here, we present the results of a study in sugarcane fields receiving different fertilizer regimes comparing soil N supply rates with potential root N uptake rates. We applied microdialysis, a novel technique for in situ quantification of soil nutrient fluxes, to measure flux rates of inorganic N and amino acid N, and analyzed N uptake capacities of sugarcane roots using 15N labelled tracers. We found that in fertilized sugarcane soils, fluxes of inorganic N exceed the uptake capacities of sugarcane roots by several orders of magnitude. Contrary, fluxes of organic N closely matched roots' uptake capacity. These results indicate root uptake capacity constrains plant acquisition of inorganic N. This mismatch between soil N supply and root N uptake capacity is a likely key driver for low N efficiency in the studied crop system. Our results also suggest that the relative contribution of inorganic N for plant nutrition may be overestimated when relying on soil extracts as indicators for root-available N, and organic N may contribute more to crop N supply than is currently assumed. Overall, we show a new approach for examining in situ N relations in soil in context of crop N physiology, which provides a new avenue towards tailoring N fertilizer supply to match the specific uptake abilities and N demand of crops over the growth cycle.

Synergizing health and population in Pakistan.

PubMed

Nishtar, Sania; Amjad, Saba; Sheikh, Sobia; Ahmad, Mahbub

2009-09-01

The delivery of health and family planning services in Pakistan is the respective mandate of the Ministry of Health/departments of health and the Ministry of Population Welfare. This institutional separation creates issues due to marginalization of family planning and reproductive health as core health issues. The government of Pakistan has made several attempts in the past to merge both the institutional hierarchal arrangements. This study was conducted to examine if merger is a viable option and to explore a way forward to bridge the current population-health disconnect in the country. Qualitative survey methods, inclusive of review of published and grey literature, archival analysis, informant interviews and focus group discussions were used for the analysis. Findings outline both the imperatives for merging the ministries and the challenges inherent in doing so. Recommendations recognize that although not a sufficient step to improve health and population outcomes, creating synergies between the health and population sectors is an imperative. The sustainable long-term solution to the existing population-health disconnect centres on deep-rooted reform at several levels in both the institutional hierarchies, with transformation of the role of stewardship agencies and reengineering of service delivery arrangements as its hallmarks. Restructured service delivery arrangements are meant to allow the delivery of a set of MDG+ services, where family planning and reproductive health are grouped alongside and together with essential health services. The latter are envisaged to be a yardstick for public delivery of services and the basis of contractual relationships in new management arrangements, which involve a role for the private sector. The short to medium term strategies proposed in this paper centre on a range of specific collaborative measures with a view to building capacity for the broader systems transformation. Sustained political and institutional commitment will be needed to implement these recommendations.

The care delivery experience of hospitalized patients with complex chronic disease.

PubMed

Kuluski, Kerry; Hoang, Sylvia N; Schaink, Alexis K; Alvaro, Celeste; Lyons, Renee F; Tobias, Roy; Bensimon, Cécile M

2013-12-01

This study investigated what is important in care delivery from the perspective of hospital inpatients with complex chronic disease, a currently understudied population. One-on-one semi-structured interviews were conducted with inpatients at a continuing care/rehabilitation hospital (n = 116) in Canada between February and July 2011. The study design was mixed methods and reports on patient characteristics and care delivery experiences. Basic descriptive statistics were run using SPSS version 17, and thematic analysis on the transcripts was conducted using NVivo9 software. Patients had an average of 5 morbidities and several illness symptoms including activity of daily living impairments, physical pain and emotional disturbance. Three broad themes (each with one or more subthemes) were generated from the data representing important components of care delivery: components of the care plan (a comprehensive assessment, supported transitions and a bio-psycho-social care package); care capacity and quality (optimal staff to patient ratios, quicker response times, better patient-provider communication and consistency between providers) and the patient-provider relationships (characterized by respect and dignity). As health systems throughout the industrialized world move to sustain health budgets while optimizing quality of care, it is critical to better understand this population, so that appropriate metrics, services and policies can be developed. The study has generated a body of evidence on the important components of care delivery from the perspectives of a diverse group of chronically ill individuals who have spent a considerable amount of time in the health-care system. Moving forward, exploration around the appropriate funding models and skill mix is needed to move the evidence into changed practice. © 2013 John Wiley & Sons Ltd.

Collaborative Manufacturing for Small-Medium Enterprises

NASA Astrophysics Data System (ADS)

Irianto, D.

2016-02-01

Manufacturing systems involve decisions concerning production processes, capacity, planning, and control. In a MTO manufacturing systems, strategic decisions concerning fulfilment of customer requirement, manufacturing cost, and due date of delivery are the most important. In order to accelerate the decision making process, research on decision making structure when receiving order and sequencing activities under limited capacity is required. An effective decision making process is typically required by small-medium components and tools maker as supporting industries to large industries. On one side, metal small-medium enterprises are expected to produce parts, components or tools (i.e. jigs, fixture, mold, and dies) with high precision, low cost, and exact delivery time. On the other side, a metal small- medium enterprise may have weak bargaining position due to aspects such as low production capacity, limited budget for material procurement, and limited high precision machine and equipment. Instead of receiving order exclusively, a small-medium enterprise can collaborate with other small-medium enterprise in order to fulfill requirements high quality, low manufacturing cost, and just in time delivery. Small-medium enterprises can share their best capabilities to form effective supporting industries. Independent body such as community service at university can take a role as a collaboration manager. The Laboratory of Production Systems at Bandung Institute of Technology has implemented shared manufacturing systems for small-medium enterprise collaboration.

Self-assembled peptide-based nanostructures: Smart nanomaterials toward targeted drug delivery.

PubMed

Habibi, Neda; Kamaly, Nazila; Memic, Adnan; Shafiee, Hadi

2016-02-01

Self-assembly of peptides can yield an array of well-defined nanostructures that are highly attractive nanomaterials for many biomedical applications such as drug delivery. Some of the advantages of self-assembled peptide nanostructures over other delivery platforms include their chemical diversity, biocompatibility, high loading capacity for both hydrophobic and hydrophilic drugs, and their ability to target molecular recognition sites. Furthermore, these self-assembled nanostructures could be designed with novel peptide motifs, making them stimuli-responsive and achieving triggered drug delivery at disease sites. The goal of this work is to present a comprehensive review of the most recent studies on self-assembled peptides with a focus on their "smart" activity for formation of targeted and responsive drug-delivery carriers.

The challenges of reshaping disease specific and care oriented community based services towards comprehensive goals: a situation appraisal in the Western Cape Province, South Africa.

PubMed

Schneider, Helen; Schaay, Nikki; Dudley, Lilian; Goliath, Charlyn; Qukula, Tobeka

2015-09-30

Similar to other countries in the region, South Africa is currently reorienting a loosely structured and highly diverse community care system that evolved around HIV and TB, into a formalized, comprehensive and integrated primary health care outreach programme, based on community health workers (CHWs). While the difficulties of establishing national CHW programmes are well described, the reshaping of disease specific and care oriented community services, based outside the formal health system, poses particular challenges. This paper is an in-depth case study of the challenges of implementing reforms to community based services (CBS) in one province of South Africa. A multi-method situation appraisal of CBS in the Western Cape Province was conducted over eight months in close collaboration with provincial stakeholders. The appraisal mapped the roles and service delivery, human resource, financing and governance arrangements of an extensive non-governmental organisation (NGO) contracted and CHW based service delivery infrastructure that emerged over 15-20 years in this province. It also gathered the perspectives of a wide range of actors - including communities, users, NGOs, PHC providers and managers - on the current state and future visions of CBS. While there was wide support for new approaches to CBS, there are a number of challenges to achieving this. Although largely government funded, the community based delivery platform remains marginal to the formal public primary health care (PHC) and district health systems. CHW roles evolved from a system of home based care and are limited in scope. There is a high turnover of cadres, and support systems (supervision, monitoring, financing, training), coordination between CHWs, NGOs and PHC facilities, and sub-district capacity for planning and management of CBS are all poorly developed. Reorienting community based services that have their origins in care responses to HIV and TB presents an inter-related set of resource mobilisation, system design and governance challenges. These include not only formalising community based teams themselves, but also the forging of new roles, relationships and mind-sets within the primary health care system, and creating greater capacity for contracting and engaging a plural set of actors - government, NGO and community - at district and sub-district level.

Northeast Conference on Rural HIV Service Delivery (Burlington, Vermont, October 23-24, 2000). Summary Report.

ERIC Educational Resources Information Center

McKinney, Martha M.

The Northeast Conference on Rural HIV Service Delivery was attended by 51 health and social service professionals, people with HIV, and federal and state health officials with expertise or interest in developing HIV care capacity in rural areas. Low population density, low prevalence of HIV/AIDS, rugged topography and climate, and limited health…

Protamine-based nanoparticles as new antigen delivery systems.

PubMed

González-Aramundiz, José Vicente; Peleteiro Olmedo, Mercedes; González-Fernández, África; Alonso Fernández, María José; Csaba, Noemi Stefánia

2015-11-01

The use of biodegradable nanoparticles as antigen delivery vehicles is an attractive approach to overcome the problems associated with the use of Alum-based classical adjuvants. Herein we report, the design and development of protamine-based nanoparticles as novel antigen delivery systems, using recombinant hepatitis B surface antigen as a model viral antigen. The nanoparticles, composed of protamine and a polysaccharide (hyaluronic acid or alginate), were obtained using a mild ionic cross-linking technique. The size and surface charge of the nanoparticles could be modulated by adjusting the ratio of the components. Prototypes with optimal physicochemical characteristics and satisfactory colloidal stability were selected for the assessment of their antigen loading capacity, antigen stability during storage and in vitro and in vivo proof-of-concept studies. In vitro studies showed that antigen-loaded nanoparticles induced the secretion of cytokines by macrophages more efficiently than the antigen in solution, thus indicating a potential adjuvant effect of the nanoparticles. Finally, in vivo studies showed the capacity of these systems to trigger efficient immune responses against the hepatitis B antigen following intramuscular administration, suggesting the potential interest of protamine-polysaccharide nanoparticles as antigen delivery systems. Copyright © 2015 Elsevier B.V. All rights reserved.

Preventing vertical transmission of HIV in Kinshasa, Democratic Republic of the Congo: a baseline survey of 18 antenatal clinics.

PubMed

Behets, Frieda Mtf; Matendo, Richard; Vaz, Lara Me; Kilese, Nick; Nanlele, Diderot; Kokolomami, Jack; Okitolando, Emile W; Van Rie, Annelies

2006-12-01

To assess the content and delivery of essential antenatal services before implementation of programmes for prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV). We assessed 18 antenatal care centres (eight public units and ten managed by nongovernmental organizations) in Kinshasa, Democratic Republic of the Congo. We used a survey to capture information about the number and type of antenatal health workers, infrastructure capacity and the delivery of basic antenatal care services such as: nutritional counselling; tetanus toxoid vaccination; prevention and management of anaemia, malaria, sexually transmitted infections, and tuberculosis; and counselling for postpartum contraception. Antenatal care units differed with respect to size, capacity, cost, service delivery systems and content. For instance, 17 of the 18 sites offered anaemia screening but only two sites included the cost in the card that gives access to antenatal care. Nine of the clinics (50%) reported providing the malaria prophyalxis sulfadoxine pyrimethamine as per national policy. Four (22%) of the sites offered syphilis screening. Scaling up PMTCT programmes in under-resourced settings requires evaluation and strengthening of existing basic antenatal care service delivery.

DNA vaccination for cervical cancer: Strategic optimisation of RALA mediated gene delivery from a biodegradable microneedle system.

PubMed

Cole, Grace; Ali, Ahlam A; McCrudden, Cian M; McBride, John W; McCaffrey, Joanne; Robson, Tracy; Kett, Vicky L; Dunne, Nicholas J; Donnelly, Ryan F; McCarthy, Helen O

2018-06-01

Dissolvable microneedles can be employed to deliver DNA to antigen presenting cells within the skin. However, this technology faces two main challenges: the poor transfection efficacy of pDNA following release from the microneedle matrix, and the limited loading capacity of the micron-scale devices. Two-tier delivery systems combining microneedle platforms and DNA delivery vectors have increased efficacy but the challenge of increasing the loading capacity remains. This study utilised lyophilisation to increase the loading of RALA/pDNA nanoparticles within dissolvable PVA microneedles. As a result, delivery was significantly enhanced in vivo into an appropriate range for DNA vaccination (∼50 μg per array). Furthermore, modifying the manufacturing process was not detrimental to the microneedle mechanical properties or cargo functionality. It was demonstrated that arrays retained mechanical and functional stability over short term storage, and were able to elicit gene expression in vitro and in vivo. Finally, treatment with this novel formulation significantly retarded the growth of established tumours, and proved superior to standard intramuscular injection in a preclinical model of cervical cancer. Copyright © 2018 Elsevier B.V. All rights reserved.

Effect of Modulated Alternating and Direct Current Iontophoresis on Transdermal Delivery of Lidocaine Hydrochloride

PubMed Central

Banga, Ajay K.

2014-01-01

The objective of this study was to investigate the iontophoretic delivery of lidocaine hydrochloride through porcine skin and to compare the effects of modulated alternating and direct current iontophoresis. Continuous and modulated iontophoresis was applied for one hour and two hours (0-1 h and 4-5th h) using a 1% w/v solution of lidocaine hydrochloride. Tape stripping was done to quantify the amount of drug permeated into stratum corneum and skin extraction studies were performed to determine the amount of drug in stripped skin. Receptor was sampled and analyzed over predefined time periods. The amount of lidocaine delivered across porcine skin after modulated direct current iontophoresis for 2 h was 1069.87 ± 120.03 μg/sq·cm compared to 744.81 ± 125.41 μg/sq·cm after modulated alternating current iontophoresis for 2 h. Modulated direct current iontophoresis also enhanced lidocaine delivery by twelvefold compared to passive delivery as 91.27 ± 18.71 μg/sq·cm of lidocaine was delivered after passive delivery. Modulated iontophoresis enhanced the delivery of lidocaine hydrochloride across porcine skin compared to the passive delivery. Modulated alternating current iontophoresis for duration of 2 h at frequency of 1 kHz was found to be comparable to the continuous direct current iontophoresis for 1 h. PMID:24959580

Effect of modulated alternating and direct current iontophoresis on transdermal delivery of lidocaine hydrochloride.

PubMed

Bhatia, Gaurav; Banga, Ajay K

2014-01-01

The objective of this study was to investigate the iontophoretic delivery of lidocaine hydrochloride through porcine skin and to compare the effects of modulated alternating and direct current iontophoresis. Continuous and modulated iontophoresis was applied for one hour and two hours (0-1 h and 4-5th h) using a 1% w/v solution of lidocaine hydrochloride. Tape stripping was done to quantify the amount of drug permeated into stratum corneum and skin extraction studies were performed to determine the amount of drug in stripped skin. Receptor was sampled and analyzed over predefined time periods. The amount of lidocaine delivered across porcine skin after modulated direct current iontophoresis for 2 h was 1069.87 ± 120.03 μ g/sq · cm compared to 744.81 ± 125.41 μ g/sq · cm after modulated alternating current iontophoresis for 2 h. Modulated direct current iontophoresis also enhanced lidocaine delivery by twelvefold compared to passive delivery as 91.27 ± 18.71 μ g/sq · cm of lidocaine was delivered after passive delivery. Modulated iontophoresis enhanced the delivery of lidocaine hydrochloride across porcine skin compared to the passive delivery. Modulated alternating current iontophoresis for duration of 2 h at frequency of 1 kHz was found to be comparable to the continuous direct current iontophoresis for 1 h.

Vaccine vial stopper performance for fractional dose delivery of vaccines.

PubMed

Jarrahian, Courtney; Myers, Daniel; Creelman, Ben; Saxon, Eugene; Zehrung, Darin

2017-07-03

Shortages of vaccines such as inactivated poliovirus and yellow fever vaccines have been addressed by administering reduced-or fractional-doses, as recommended by the World Health Organization Strategic Advisory Group of Experts on Immunization, to expand population coverage in countries at risk. We evaluated 3 kinds of vaccine vial stoppers to assess their performance after increased piercing from repeated withdrawal of doses needed when using fractional doses (0.1 mL) from presentations intended for full-dose (0.5 mL) delivery. Self-sealing capacity and fragmentation of the stopper were assessed via modified versions of international standard protocols. All stoppers maintained self-sealing capacity after 100 punctures. The damage to stoppers measured as the fragmentation rate was within the target of ≤ 10% of punctures resulting in a fragment after as many as 50 punctures. We concluded that stopper failure is not likely to be a concern if existing vaccine vials containing up to 10 regular doses are used up to 50 times for fractional dose delivery.

Development of New Transportation/Storage Cask System for Use by DOE Russian Research Reactor Fuel Return Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Michael Tyacke; Frantisek Svitak; Jiri Rychecky

2010-04-01

The United States, the Russian Federation, and the International Atomic Energy Agency (IAEA) have been working together on a program called the Russian Research Reactor Fuel Return (RRRFR) Program. The purpose of this program is to return Soviet or Russian supplied high-enriched uranium (HEU) fuel currently stored at Russian-designed research reactors throughout the world to Russia. To accommodate transport of the HEU spent nuclear fuel (SNF), a new large-capacity transport/storage cask system was specially designed for handling and operations under the unique conditions for these research reactor facilities. This new cask system is named the ŠKODA VPVR/M cask. The design,more » licensing, testing, and delivery of this new cask system are the results of a significant international cooperative effort by several countries and involved numerous private and governmental organizations. This paper contains the following sections: (1) Introduction/Background; (2) VPVR/M Cask Description; (3) Ancillary Equipment, (4) Cask Licensing; (5) Cask Demonstration and Operations; (6) IAEA Procurement, Quality Assurance Inspections, Fabrication, and Delivery; and, (7) Summary and Conclusions.« less

Development of a New Transportation/Storage Cask System for Use by the DOE Russian Research Reactor Fuel Return Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Michael J. Tyacke; Frantisek Svitak; Jiri Rychecky

2007-10-01

The United States, the Russian Federation, and the International Atomic Energy Agency (IAEA) have been working together on a program called the Russian Research Reactor Fuel Return (RRRFR) Program. The purpose of this program is to return Soviet or Russian-supplied high-enriched uranium (HEU) fuel, currently stored at Russian-designed research reactors throughout the world, to Russia. To accommodate transport of the HEU spent nuclear fuel (SNF), a new large-capacity transport/storage cask system was specially designed for handling and operations under the unique conditions at these research reactor facilities. This new cask system is named the ŠKODA VPVR/M cask. The design, licensing,more » testing, and delivery of this new cask system result from a significant international cooperative effort by several countries and involved numerous private and governmental organizations. This paper contains the following sections: 1) Introduction; 2) VPVR/M Cask Description; 3) Ancillary Equipment, 4) Cask Licensing; 5) Cask Demonstration and Operations; 6) IAEA Procurement, Quality Assurance Inspections, Fabrication, and Delivery; and, 7) Conclusions.« less

A proposal for cervical screening information systems in developing countries.

PubMed

Marrett, Loraine D; Robles, Sylvia; Ashbury, Fredrick D; Green, Bo; Goel, Vivek; Luciani, Silvana

2002-11-20

The effective and efficient delivery of cervical screening programs requires information for planning, management, delivery and evaluation. Specially designed systems are generally required to meet these needs. In many developing countries, lack of information systems constitutes an important barrier to development of comprehensive screening programs and the effective control of cervical cancer. Our report outlines a framework for creating such systems in developing countries and describes a conceptual model for a cervical screening information system. The proposed system is modular, recognizing that there will be considerable between-region heterogeneity in current status and priorities. The proposed system is centered on modules that would allow for the assembly and computerization of data on Pap tests, since these represent the main screening modality at the present time. Additional modules would process data and create and maintain a screening database (e.g., standardize, edit, link and update modules) and allow for the integration of other types of data, such as cervical histopathology results. An open systems development model is proposed, since it is most compatible with the goals of local stakeholder involvement and capacity-building. Copyright 2002 Wiley-Liss, Inc.

Introducing health gains in location-allocation models: A stochastic model for planning the delivery of long-term care

NASA Astrophysics Data System (ADS)

Cardoso, T.; Oliveira, M. D.; Barbosa-Póvoa, A.; Nickel, S.

2015-05-01

Although the maximization of health is a key objective in health care systems, location-allocation literature has not yet considered this dimension. This study proposes a multi-objective stochastic mathematical programming approach to support the planning of a multi-service network of long-term care (LTC), both in terms of services location and capacity planning. This approach is based on a mixed integer linear programming model with two objectives - the maximization of expected health gains and the minimization of expected costs - with satisficing levels in several dimensions of equity - namely, equity of access, equity of utilization, socioeconomic equity and geographical equity - being imposed as constraints. The augmented ε-constraint method is used to explore the trade-off between these conflicting objectives, with uncertainty in the demand and delivery of care being accounted for. The model is applied to analyze the (re)organization of the LTC network currently operating in the Great Lisbon region in Portugal for the 2014-2016 period. Results show that extending the network of LTC is a cost-effective investment.

Assessment of Alternative Student and Delivery Systems: Assessment of the Current Delivery System. Supplement I to the Final Report.

ERIC Educational Resources Information Center

Advanced Technology, Inc., Reston, VA.

The effects of the current student financial aid delivery system on five major participant groups are examined: federal government, states/guarantee agencies, postsecondary institutions, lenders and secondary markets, and applicants and families. Attention is directed to effects of the current system, including: administrative costs, fund…

High efficient anti-cancer drug delivery systems using tea polyphenols reduced and functionalized graphene oxide.

PubMed

Wang, Xiaoqian; Hao, Liying; Zhang, Chaoliang; Chen, Jiao; Zhang, Ping

2017-03-01

Targeted drug delivery is urgently needed for cancer therapy, and green synthesis is important for the biomedical use of drug delivery systems in the human body. In this work, we report two targeted delivery systems for anticancer drugs based on tea polyphenol functionalized and reduced graphene oxide (TPGs). The obtained TPGs demonstrated an efficient doxorubicin loading capacity as high as 3.430 × 10 6  mg g -1 and 3.932 × 10 4  mg g -1 , and exhibited pH-triggered release. Furthermore, the kinetic models, adsorption isotherms, and possible loading mechanisms were investigated in details. Compared to TPG1 and free doxorubicin, TPG2 is biocompatible to normal cells even at high concentrations and promotes tumor cells death by delivering the doxorubicin mainly to the nuclei. These results were confirmed using cell viability tests and confocal laser microscopy. Moreover, apoptosis tests showed that the mechanism of cancer cell death induced by TPG1 and TPG2 might follow the similar mechanisms. Taken together, these results demonstrate that TPGs provide a multifunctional drug delivery system with a greater loading capacity and pH-sensitive drug release for enhanced cancer therapy. The high drug payload capability and enhanced antitumor efficacy demonstrate that we developed systems are promising for various biomedical applications and cancer therapy.

Muscle stem cell intramuscular delivery within hyaluronan methylcellulose improves engraftment efficiency and dispersion.

PubMed

Davoudi, Sadegh; Chin, Chih-Ying; Cooke, Michael J; Tam, Roger Y; Shoichet, Molly S; Gilbert, Penney M

2018-04-26

Adult skeletal muscle tissue harbors the capacity for self-repair due to the presence of tissue resident muscle stem cells (MuSCs). Advances in the area of prospective MuSC isolation demonstrated the potential of cell transplantation therapy as a regenerative medicine strategy to restore strength and long-term regenerative capacity to aged, injured, or diseased skeletal muscle tissue. However, cell loss during ejection, limits to post-injection proliferation, and poor donor cell dispersion distal to the injection site are amongst hurdles to overcome to maximize MuSC transplant impact. Here, we assess a physical blend of hyaluronan and methylcellulose (HAMC) as a bioactive, shear thinning hydrogel cell delivery system to improve MuSC transplantation efficiency. Using in vivo transplantation studies, we found that the HAMC delivery system results in a >45% increase in the number of donor-derived fibers as compared to saline delivery. We demonstrate that increases in donor-derived fibers when using HAMC are attributed to increased MuSC proliferation via a CD44-independent mechanism, preventing injected cell active clearance, and supporting in vivo expansion by delaying differentiation. Furthermore, we observed a significant improvement in donor fiber dispersion when MuSCs were delivered in HAMC. Our study results suggest that HAMC is a promising muscle stem cell delivery vehicle. Copyright © 2018 Elsevier Ltd. All rights reserved.

Delivery of Small Interfering RNA by Peptide-Targeted Mesoporous Silica Nanoparticle-Supported Lipid Bilayers

PubMed Central

Ashley, Carlee E.; Carnes, Eric C.; Epler, Katharine E.; Padilla, David P.; Phillips, Genevieve K.; Castillo, Robert E.; Wilkinson, Dan C.; Wilkinson, Brian S.; Burgard, Cameron A.; Sewell, Robin M.; Townson, Jason L.; Chackerian, Bryce; Willman, Cheryl L.; Peabody, David S.; Wharton, Walker; Brinker, C. Jeffrey

2012-01-01

The therapeutic potential of small interfering RNAs (siRNAs) is severely limited by the availability of delivery platforms that protect siRNA from degradation, deliver it to the target cell with high specificity and efficiency, and promote its endosomal escape and cytosolic dispersion. Here we report that mesoporous silica nanoparticle-supported lipid bilayers (or ‘protocells’), exhibit multiple properties that overcome many of the limitations of existing delivery platforms. Protocells have a 10- to 100-fold greater capacity for siRNA than corresponding lipid nanoparticles and are markedly more stable when incubated under physiological conditions. Protocells loaded with a cocktail of siRNAs bind to cells in a manner dependent on the presence of an appropriate targeting peptide and, through an endocytic pathway followed by endosomal disruption, promote delivery of the silencing nucleotides to the cytoplasm. The expression of each of the genes targeted by the siRNAs was shown to be repressed at the protein level, resulting in a potent induction of growth arrest and apoptosis. Incubation of control cells that lack expression of the antigen recognized by the targeting peptide with siRNA-loaded protocells induced neither repression of protein expression nor apoptosis, indicating the precise specificity of cytotoxic activity. In terms of loading capacity, targeting capabilities, and potency of action, protocells provide unique attributes as a delivery platform for therapeutic oligonucleotides. PMID:22309035

A qualitative study of governance of evolving response to non-communicable diseases in low-and middle- income countries: current status, risks and options.

PubMed

Rani, Manju; Nusrat, Sharmin; Hawken, Laura H

2012-10-16

Segmented service delivery with consequent inefficiencies in health systems was one of the main concerns raised during scaling up of disease-specific programs in the last two decades. The organized response to NCD is in infancy in most LMICs with little evidence on how the response is evolving in terms of institutional arrangements and policy development processes. Drawing on qualitative review of policy and program documents from five LMICs and data from global key-informant surveys conducted in 2004 and 2010, we examine current status of governance of response to NCDs at national level along three dimensions- institutional arrangements for stewardship and program management and implementation; policies/plans; and multisectoral coordination and partnerships. Several positive trends were noted in the organization and governance of response to NCDs: shift from specific NCD-based programs to integrated NCD programs, increasing inclusion of NCDs in sector-wide health plans, and establishment of high-level multisectoral coordination mechanisms.Several areas of concern were identified. The evolving NCD-specific institutional structures are being treated as 'program management and implementation' entities rather than as lead 'technical advisory' bodies, with unclear division of roles and responsibilities between NCD-specific and sector-wide structures. NCD-specific and sector-wide plans are poorly aligned and lack prioritization, costing, and appropriate targets. Finally, the effectiveness of existing multisectoral coordination mechanisms remains questionable. The 'technical functions' and 'implementation and management functions' should be clearly separated between NCD-specific units and sector-wide institutional structures to avoid duplicative segmented service delivery systems. Institutional capacity building efforts for NCDs should target both NCD-specific units (for building technical and analytical capacity) and sector-wide organizational units (for building program management and implementation capacity) in MOH.The sector-wide health plans should reflect NCDs in proportion to their public health importance. NCD specific plans should be developed in close consultation with sector-wide health- and non-health stakeholders. These plans should expand on the directions provided by sector-wide health plans specifying strategically prioritized, fully costed activities, and realistic quantifiable targets for NCD control linked with sector-wide expenditure framework. Multisectoral coordination mechanisms need to be strengthened with optimal decision-making powers and resource commitment and monitoring of their outputs.

A qualitative study of governance of evolving response to non-communicable diseases in low-and middle- income countries: current status, risks and options

PubMed Central

2012-01-01

Background Segmented service delivery with consequent inefficiencies in health systems was one of the main concerns raised during scaling up of disease-specific programs in the last two decades. The organized response to NCD is in infancy in most LMICs with little evidence on how the response is evolving in terms of institutional arrangements and policy development processes. Methods Drawing on qualitative review of policy and program documents from five LMICs and data from global key-informant surveys conducted in 2004 and 2010, we examine current status of governance of response to NCDs at national level along three dimensions— institutional arrangements for stewardship and program management and implementation; policies/plans; and multisectoral coordination and partnerships. Results Several positive trends were noted in the organization and governance of response to NCDs: shift from specific NCD-based programs to integrated NCD programs, increasing inclusion of NCDs in sector-wide health plans, and establishment of high-level multisectoral coordination mechanisms. Several areas of concern were identified. The evolving NCD-specific institutional structures are being treated as ‘program management and implementation’ entities rather than as lead ‘technical advisory’ bodies, with unclear division of roles and responsibilities between NCD-specific and sector-wide structures. NCD-specific and sector-wide plans are poorly aligned and lack prioritization, costing, and appropriate targets. Finally, the effectiveness of existing multisectoral coordination mechanisms remains questionable. Conclusions The ‘technical functions’ and ‘implementation and management functions’ should be clearly separated between NCD-specific units and sector-wide institutional structures to avoid duplicative segmented service delivery systems. Institutional capacity building efforts for NCDs should target both NCD-specific units (for building technical and analytical capacity) and sector-wide organizational units (for building program management and implementation capacity) in MOH. The sector-wide health plans should reflect NCDs in proportion to their public health importance. NCD specific plans should be developed in close consultation with sector-wide health- and non-health stakeholders. These plans should expand on the directions provided by sector-wide health plans specifying strategically prioritized, fully costed activities, and realistic quantifiable targets for NCD control linked with sector-wide expenditure framework. Multisectoral coordination mechanisms need to be strengthened with optimal decision-making powers and resource commitment and monitoring of their outputs. PMID:23067232

Thermal treatment of galactose-branched polyelectrolyte microcapsules to improve drug delivery with reserved targetability.

PubMed

Zhang, Fu; Wu, Qi; Liu, Li-Jun; Chen, Zhi-Chun; Lin, Xian-Fu

2008-06-05

A novel multilayered drug delivery system by LbL assembly of galactosylated polyelectrolyte, which is possible to have the potential in hepatic targeting by the presence of galactose residues at the microcapsule's surface, is designed. Thermal treatment was performed on the capsules and a dramatic thermal shrinkage up to 60% decrease of capsule diameter above 50 degrees C was observed. This thermal behavior was then used to manipulate drug loading capacity and release rate. Heating after drug loading could seal the capsule shell, enhancing the loading capacity and reducing the release rate significantly. Excellent affinity between galactose-binding lectin and heated galactose-containing microcapsules were observed, indicating a stable targeting potential even after high temperature elevating up to 90 degrees C.

A completely automated flow, heat-capacity, calorimeter for use at high temperatures and pressures

NASA Astrophysics Data System (ADS)

Rogers, P. S. Z.; Sandarusi, Jamal

1990-11-01

An automated, flow calorimeter has been constructed to measure the isobaric heat capacities of concentrated, aqueous electrolyte solutions using a differential calorimetry technique. The calorimeter is capable of operation to 700 K and 40 MPa with a measurement accuracy of 0.03% relative to the heat capacity of the pure reference fluid (water). A novel design encloses the calorimeter within a double set of separately controlled, copper, adiabatic shields that minimize calorimeter heat losses and precisely control the temperature of the inlet fluids. A multistage preheat train, used to efficiently heat the flowing fluid, includes a counter-current heat exchanger for the inlet and outlet fluid streams in tandem with two calorimeter preheaters. Complete system automation is accomplished with a distributed control scheme using multiple processors, allowing the major control tasks of calorimeter operation and control, data logging and display, and pump control to be performed simultaneously. A sophisticated pumping strategy for the two separate syringe pumps allows continuous fluid delivery. This automation system enables the calorimeter to operate unattended except for the reloading of sample fluids. In addition, automation has allowed the development and implementation of an improved heat loss calibration method that provides calorimeter calibration with absolute accuracy comparable to the overall measurement precision, even for very concentrated solutions.

Expressing Transgenes That Exceed the Packaging Capacity of Adeno-Associated Virus Capsids

PubMed Central

Chamberlain, Kyle; Riyad, Jalish Mahmud; Weber, Thomas

2016-01-01

Recombinant adeno-associated virus vectors (rAAV) are being explored as gene delivery vehicles for the treatment of various inherited and acquired disorders. rAAVs are attractive vectors for several reasons: wild-type AAVs are nonpathogenic, and rAAVs can trigger long-term transgene expression even in the absence of genome integration—at least in postmitotic tissues. Moreover, rAAVs have a low immunogenic profile, and the various AAV serotypes and variants display broad but distinct tropisms. One limitation of rAAVs is that their genome-packaging capacity is only ∼5 kb. For most applications this is not of major concern because the median human protein size is 375 amino acids. Excluding the ITRs, for a protein of typical length, this allows the incorporation of ∼3.5 kb of DNA for the promoter, polyadenylation sequence, and other regulatory elements into a single AAV vector. Nonetheless, for certain diseases the packaging limit of AAV does not allow the delivery of a full-length therapeutic protein by a single AAV vector. Hence, approaches to overcome this limitation have become an important area of research for AAV gene therapy. Among the most promising approaches to overcome the limitation imposed by the packaging capacity of AAV is the use of dual-vector approaches, whereby a transgene is split across two separate AAV vectors. Coinfection of a cell with these two rAAVs will then—through a variety of mechanisms—result in the transcription of an assembled mRNA that could not be encoded by a single AAV vector because of the DNA packaging limits of AAV. The main purpose of this review is to assess the current literature with respect to dual-AAV-vector design, to highlight the effectiveness of the different methodologies and to briefly discuss future areas of research to improve the efficiency of dual-AAV-vector transduction. PMID:26757051

Graphene as multifunctional delivery platform in cancer therapy.

PubMed

Nejabat, Mojgan; Charbgoo, Fahimeh; Ramezani, Mohammad

2017-08-01

The biomedical applications of graphene-based nanomaterials including drug and gene delivery have grown rapidly in the past few years. This is due to its high surface area that results in high cargo loading capacity. It is demonstrated that graphene can improve drug efficacy without increasing the dose of the chemotherapeutic agent in cancer treatment. Considering these valuable benefits of graphene, this review focused on the newest advancements in drug and gene delivery systems using graphene and unveiling advantages and disadvantages of different graphene-based materials in introducing an effective cargo delivery system for cancer therapy. Different approaches for reducing cytotoxic impacts of graphene oxide and production of biocompatible delivery platform were also reviewed. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2355-2367, 2017. © 2017 Wiley Periodicals, Inc.

Noncovalent interaction-assisted drug delivery system with highly efficient uptake and release of paclitaxel for anticancer therapy.

PubMed

Wei, Yuping; Ma, Liang; Zhang, Liang; Xu, Xia

2017-01-01

An effective drug delivery system requires efficient drug uptake and release inside cancer cells. Here, we report a novel drug delivery system, in which paclitaxel (PTX) interacts with a novel cell penetrating peptide (CPP) through noncovalent interaction designed based on molecular simulations. This CPP/PTX complex confers high efficiency in delivering PTX into cancer cells not by endocytosis but by an energy-independent pathway. Once inside cells, the noncovalent interaction between PTX and the CPP may allow fast release of PTX within cells due to the direct translocation of CPP/PTX. This drug delivery system exhibits strong capacity for inhibition of tumor growth and offers a new avenue for the development of advanced drug delivery systems for anticancer therapy.

Current and emerging formulation strategies for the effective transdermal delivery of HIV inhibitors.

PubMed

Ham, Anthony S; Buckheit, Robert W

2015-02-01

Current and emerging formulation strategies for skin permeation are poised to open the transdermal drug delivery to a broader range of small molecule compounds that do not fit the traditional requirements for successful transdermal drug delivery, allowing the development of new patch technologies to deliver antiretroviral drugs that were previously incapable of being delivered through transdermal means. Transdermal drug delivery offers several distinct advantages over traditional dosage forms. Current antiretroviral drugs used for the treatment of HIV infection include a variety of highly active small molecule compounds with significantly limited skin permeability, and thus new and novel means of enhancing transport through the skin are needed. Current and emerging formulation strategies are poised to open the transdermal drug delivery to a broader range of compounds that do not fit the traditional requirements for successful transdermal drug delivery, allowing the development of new patch technologies to deliver antiretroviral drugs that were previously incapable of being delivered through transdermal means. Thus, with continuing research into skin permeability and patch formulation strategies, there is a large potential for antiretroviral transdermal drug delivery.

Current and emerging formulation strategies for the effective transdermal delivery of HIV inhibitors

PubMed Central

Ham, Anthony S; Buckheit, Robert W

2015-01-01

Current and emerging formulation strategies for skin permeation are poised to open the transdermal drug delivery to a broader range of small molecule compounds that do not fit the traditional requirements for successful transdermal drug delivery, allowing the development of new patch technologies to deliver antiretroviral drugs that were previously incapable of being delivered through transdermal means. Transdermal drug delivery offers several distinct advantages over traditional dosage forms. Current antiretroviral drugs used for the treatment of HIV infection include a variety of highly active small molecule compounds with significantly limited skin permeability, and thus new and novel means of enhancing transport through the skin are needed. Current and emerging formulation strategies are poised to open the transdermal drug delivery to a broader range of compounds that do not fit the traditional requirements for successful transdermal drug delivery, allowing the development of new patch technologies to deliver antiretroviral drugs that were previously incapable of being delivered through transdermal means. Thus, with continuing research into skin permeability and patch formulation strategies, there is a large potential for antiretroviral transdermal drug delivery. PMID:25690088

Improving the delivery of veterinary services in India.

PubMed

Rao, S V N; Rasheed Sulaiman, V; Natchimuthu, K; Ramkumar, S; Sasidhar, P V K

2015-12-01

In pursuit of effective veterinary service delivery, the objectives of this study were threefold: (i) reduce the shortage of technical personnel in veterinary universities (VUs) and animal husbandry departments (AHDs), (ii) identify collaborative areas between VUs and AHDs, and (iii) build the capacity of the veterinary and animal husbandry sector. Primary data were collected from all the 16 veterinary colleges and AHDs in five south Indian states on: (i) student intake and the out-turn of veterinary graduates, (ii) technical personnel--existing and required at various levels, (iii) specific areas of collaboration where VUs and AHDs need each other and can extend support to each other, and (iv) areas in which university faculty and field veterinarians would benefit from further training. Two focus group discussions were held with top administrators of VUs and AHDs to collect qualitative data. The results revealed that there are not enough veterinary graduates to meet the needs of the system and that there is a shortage of faculty, field veterinarians and para-veterinarians. Both focus groups identified areas for collaboration and capacity building to improve veterinary service delivery. The results conclusively demonstrated that India's veterinary service delivery is constrained, not due to a lack of organisations or programmes, but due to the inability of the organisations to collaborate with each other. To improve the effectiveness of veterinary service delivery it will be necessary to: admit more graduate students, support the establishment of new colleges; recruit faculty, field veterinarians and para-veterinarians; remandate the Directorates of Extension at VUs to develop linkages with AHDs; allocate funds ('special central grants') for infrastructure development to all AHDs and veterinary colleges; establish one model veterinary college that follows international standards on veterinary education and create four regional academic staff training colleges exclusively for the purpose of developing the capacity of the veterinary and animal husbandry sector. Action plans to implement these recommendations are also suggested.

Mapping the ecosystem service delivery chain: Capacity, flow, and demand pertaining to aesthetic experiences in mountain landscapes.

PubMed

Egarter Vigl, Lukas; Depellegrin, Daniel; Pereira, Paulo; de Groot, Rudolf; Tappeiner, Ulrike

2017-01-01

Accounting for the spatial connectivity between the provision of ecosystem services (ES) and their beneficiaries (supply-benefit chain) is fundamental to understanding ecosystem functioning and its management. However, the interrelationships of the specific chain links within ecosystems and the actual benefits that flow from natural landscapes to surrounding land have rarely been analyzed. We present a spatially explicit model for the analysis of one cultural ecosystem service (aesthetic experience), which integrates the complete ecosystem service delivery chain for Puez-Geisler Nature Park (Italy): (1) The potential service stock (ES capacity) relies on an expert-based land use ranking matrix, (2) the actual supply (ES flow) is based on visibility properties of observation points along recreational routes, (3) the beneficiaries of the service (ES demand) are derived from socioeconomic data as a measure of the visitation rate to the recreation location, and (4) the supply-demand relationship (ES budget) addresses the spatially explicit oversupply and undersupply of ES. The results indicate that potential ES stocks are substantially higher in core and buffer zones of protected areas than in surrounding land owing to the specific landscape composition. ES flow maps reveal service delivery to 80% of the total area studied, with the highest actual service supply to locations with long and open vistas. ES beneficiary analyses show the highest demand for aesthetic experiences in all-season tourist destinations like Val Badia and Val Gardena, where both recreational amenity and overnight stays are equally high. ES budget maps identify ES hot and cold spots in terms of ES delivery, and they highlight ES undersupply in nature protection buffer zones although they are characterized by highest ES capacity. We show how decision/policy makers can use the presented methodology to plan landscape protection measures and develop specific regulation strategies for visitors based on the ES delivery chain concept. Copyright © 2016 Elsevier B.V. All rights reserved.

Evolution and Revolutions of Adult Learning: Capacity Building in Adult and Non-Formal Education in Nigeria

ERIC Educational Resources Information Center

Ugwu, Chinwe U.

2015-01-01

The National Commission for Mass Literacy, Adult and Non-Formal Education (NMEC) is the Federal Statutory Agency set up to co-ordinate all aspects of Non-Formal Education in Nigeria whether offered by government agencies or non-governmental organisations. This study looked at the existing Capacity Building Programme, the delivery methods, impact…

Supramolecular hydrogel formation between chitosan and hydroxypropyl β-cyclodextrin via Diels-Alder reaction and its drug delivery.

PubMed

Zhang, Mengke; Wang, Jinpeng; Jin, Zhengyu

2018-07-15

Chitosan-cyclodextrin hydrogel (CFCD) was prepared via Diels-Alder reaction between furfural functionalized chitosan (CF) and N-maleoyl alanine functionalized hydroxypropyl β-cyclodextrin (HPCD-AMI) in aqueous media without any catalyst or initiator. The CF and HPCD-AMI were confirmed by Fourier transform infrared spectroscopy and 1 H nuclear magnetic resonance spectroscopy. The resultant CFCD hydrogel was characterized in terms of thermal peripteries, microstructure, rheology behavior, and swelling capacity. The rheology analysis found that the storage modulus G' ranged from 1pa to 1200pa as the degree of furfural substitute on chitosan increased from 2.6% to 28.3%, indicating the hydrogel strength can be tuned readily by reaction stoichiometry. The swelling behaviors proved that CFCD hydrogel was pH-responsive with low swelling capacity, which would be preferable for drug delivery. Drug adsorption analysis showed the introduction of cyclodextrin into CFCD hydrogels promoted drug adsorption capacity. In addition, methyl orange cumulative release in PBS buffer was only 48.85% after 24h, suggesting CFCD hydrogel had good sustained release capacity on the loaded drug. Copyright © 2018 Elsevier B.V. All rights reserved.

Impact evaluation of a health promotion-focused organisational development strategy on a health service's capacity to deliver comprehensive primary health care.

PubMed

Costello, Michelle; Taylor, Jane; O'Hara, Lily

2015-01-01

A comprehensive primary health care approach is required to address complex health issues and reduce inequities. However, there has been limited uptake of this approach by health services nationally or internationally. Reorienting health services towards becoming more health promoting provides a mechanism to support the delivery of comprehensive primary health care. The aim of this study was to determine the impact of a health promotion-focused organisational development strategy on the capacity of a primary health care service to deliver comprehensive primary health care. A questionnaire and semistructured individual interviews were used to collect quantitative and qualitative impact evaluation data, respectively, from 13 health service staff across three time points with regard to 37 indicators of organisational capacity. There were significant increases in mean scores for 31 indicators, with effect sizes ranging from moderate to nearly perfect. A range of key enablers and barriers to support the delivery of comprehensive primary health care was identified. In conclusion, an organisational development strategy to reorient health services towards becoming more health promoting may increase the capacity to deliver comprehensive primary health care.

Building capacity and resilience in the dementia care workforce: a systematic review of interventions targeting worker and organizational outcomes.

PubMed

Elliott, Kate-Ellen J; Scott, Jennifer L; Stirling, Christine; Martin, Angela J; Robinson, Andrew

2012-06-01

Dementia increasingly impacts every health and social care system in the world. Preparing the dementia care workforce is therefore paramount, particularly in light of existing problems of staff retention and turnover. Training interventions will need to increase worker and organizational capacity to deliver effective patient care. It is not clear which training interventions best enhance workers' capacity. A review of the evidence for dementia care training interventions to enhance worker capacity and facilitate organizational change is presented. A systematic literature review was conducted. All selected randomized intervention studies aimed to enhance some aspect of dementia care worker or workforce capacity such as knowledge of dementia, psychological well-being, work performance, and organizational factors such as retention or service delivery in dementia care. Seventy-four relevant studies were identified, but only six met inclusion criteria for the review. The six studies selected focused on worker and organizational outcomes in dementia care. All interventions were multi-component with dementia education or instructional training most commonly adopted. No interventions were found for the community setting. Variable effects were found for intervention outcomes and methodological concerns are raised. The rigor of scientific research in training interventions that aim to build capacity of dementia care workers is poor and a strong need exists for evaluation and delivery of such interventions in the community sphere. Wider domains of interest such as worker psychological health and well-being need to be examined further, to understand capacity-building in the dementia care workforce.

Development of renal-targeted vectors through combined in vivo phage display and capsid engineering of adenoviral fibers from serotype 19p.

PubMed

Denby, Laura; Work, Lorraine M; Seggern, Dan J Von; Wu, Eugene; McVey, John H; Nicklin, Stuart A; Baker, Andrew H

2007-09-01

The potential efficacy of gene delivery is dictated by the infectivity profile of existing vectors, which is often restrictive. In order to target cells and organs for which no efficient vector is currently available, a promising approach would be to engineer vectors with novel transduction profiles. Applications that involve injecting adenovirus (Ad) vectors into the bloodstream require that native tropism for the liver be removed, and that targeting moieties be engineered into the capsid. We previously reported that pseudotyping the Ad serotype 5 fiber for that of Ad19p results in reduced hepatic transduction. In this study we show that this may be caused, at least in part, by a reduction in the capacity of the Ad19p-based virus to bind blood coagulation factors. It is therefore a potential candidate for vector retargeting, focusing on the kidney as a therapeutic target. We used in vivo phage display in rats, and identified peptides HTTHREP and HITSLLS that homed to the kidneys following intravenous injection. We engineered the HI loop of Ad19p to accommodate peptide insertions and clones. Intravenous delivery of each peptide-modified virus resulted in selective renal targeting, with HTTHREP and HITSLLS-targeted viruses selectively transducing tubular epithelium and glomeruli, respectively. Our study has important implications for the use of genetic engineering of Ad fibers to produce targeted gene delivery vectors.

Biomimetics in drug delivery systems: A critical review.

PubMed

Sheikhpour, Mojgan; Barani, Leila; Kasaeian, Alibakhsh

2017-05-10

Today, the advanced drug delivery systems have been focused on targeted drug delivery fields. The novel drug delivery is involved with the improvement of the capacity of drug loading in drug carriers, cellular uptake of drug carriers, and the sustained release of drugs within target cells. In this review, six groups of therapeutic drug carriers including biomimetic hydrogels, biomimetic micelles, biomimetic liposomes, biomimetic dendrimers, biomimetic polymeric carriers and biomimetic nanostructures, are studied. The subject takes advantage of the biomimetic methods of productions or the biomimetic techniques for the surface modifications, similar to what accrues in natural cells. Moreover, the effects of these biomimetic approaches for promoting the drug efficiency in targeted drug delivery are visible. The study demonstrates that the fabrication of biomimetic nanocomposite drug carriers could noticeably promote the efficiency of drugs in targeted drug delivery systems. Copyright © 2017 Elsevier B.V. All rights reserved.

Advances of blood cell-based drug delivery systems.

PubMed

Sun, Yanan; Su, Jing; Liu, Geyi; Chen, Jianjun; Zhang, Xiumei; Zhang, Ran; Jiang, Minhan; Qiu, Mingfeng

2017-01-01

Blood cells, including erythrocytes, leukocytes and platelets are used as drug carriers in a wide range of applications. They have many unique advantages such as long life-span in circulation (especially erythrocytes), target release capacities (especially platelets), and natural adhesive properties (leukocytes and platelets). These properties make blood cell based delivery systems, as well as their membrane-derived carriers, far superior to other drug delivery systems. Despite the advantages, the further development of blood cell-based delivery systems was hindered by limitations in the source, storage, and mass production. To overcome these problems, synthetic biomaterials that mimic blood cell and nanocrystallization of blood cells have been developed and may represent the future direction for blood cell membrane-based delivery systems. In this paper, we review recent progress of the rising blood cell-based drug delivery systems, and also discuss their challenges and future tendency of development. Copyright © 2016. Published by Elsevier B.V.

Computer Assisted Rehabilitation Service Delivery.

ERIC Educational Resources Information Center

West Virginia Rehabilitation Research and Training Center, Dunbar.

This volume consisting of state of the art reviews, suggestions and guidelines for practitioners, and program descriptions deals with the current and potential applications of computers in the delivery of services for vocational rehabilitation (VR). Discussed first are current applications of computer technology in rehabilitative service delivery.…

Development of chitosan graft pluronic®F127 copolymer nanoparticles containing DNA aptamer for paclitaxel delivery to treat breast cancer cells

NASA Astrophysics Data System (ADS)

Thach Nguyen, Kim; Le, Duc Vinh; Do, Dinh Ho; Huan Le, Quang

2016-06-01

HER-2/ErbB2/Neu(HER-2), a member of the epidermal growth factor receptor family, is specifically overexpressed on the surface of breast cancer cells and serves a therapeutic target for breast cancer. In this study, we aimed to isolate DNA aptamer (Ap) that specifically bind to a HER-2 overexpressing SK-BR-3 human breast cancer cell line, using SELEX strategy. We developed a novel multifunctional composite micelle with surface modification of Ap for targeted delivery of paclitaxel. This binary mixed system consisting of Ap modified pluronic®F127 and chitosan could enhance PTX loading capacity and increase micelle stability. Polymeric micelles had a spherical shape and were self-assemblies of block copolymers of approximately 86.22 ± 1.45 nm diameter. PTX could be loaded with high encapsulation efficiency (83.28 ± 0.13%) and loading capacity (9.12 ± 0.34%). The release profile were 29%-35% in the first 12 h and 85%-93% after 12 d at pH 7.5 of receiving media. The IC50 doses by MTT assay showed the greater activity of nanoparticles loaded paclitaxel over free paclitaxel and killed cells up to 95% after 6 h. These results demonstrated unique assembly with the capacity to function as an efficient detection and delivery vehicle in the biological living system.

High Oxygen Delivery to Preserve Exercise Capacity in Patients with Idiopathic Pulmonary Fibrosis Treated with Nintedanib. Methodology of the HOPE-IPF Study.

PubMed

Ryerson, Christopher J; Camp, Pat G; Eves, Neil D; Schaeffer, Michele; Syed, Nafeez; Dhillon, Satvir; Jensen, Dennis; Maltais, Francois; O'Donnell, Denis E; Raghavan, Natya; Roman, Michael; Stickland, Michael K; Assayag, Deborah; Bourbeau, Jean; Dion, Genevieve; Fell, Charlene D; Hambly, Nathan; Johannson, Kerri A; Kalluri, Meena; Khalil, Nasreen; Kolb, Martin; Manganas, Helene; Morán-Mendoza, Onofre; Provencher, Steve; Ramesh, Warren; Rolf, J Douglass; Wilcox, Pearce G; Guenette, Jordan A

2016-09-01

Pulmonary rehabilitation improves dyspnea and exercise capacity in idiopathic pulmonary fibrosis (IPF); however, it is unknown whether breathing high amounts of oxygen during exercise training leads to further benefits. Herein, we describe the design of the High Oxygen Delivery to Preserve Exercise Capacity in IPF Patients Treated with Nintedanib study (the HOPE-IPF study). The primary objective of this study is to determine the physiological and perceptual impact of breathing high levels of oxygen during exercise training in patients with IPF who are receiving antifibrotic therapy. HOPE-IPF is a two-arm double-blind multicenter randomized placebo-controlled trial of 88 patients with IPF treated with nintedanib. Patients will undergo 8 weeks of three times weekly aerobic cycle exercise training, breathing a hyperoxic gas mixture with a constant fraction of 60% inhaled oxygen, or breathing up to 40% oxygen as required to maintain an oxygen saturation level of at least 88%. End points will be assessed at baseline, postintervention (Week 8), and follow-up (Week 26). The primary analysis will compare the between-group baseline with post-training change in endurance time during constant work rate cycle exercise tests. Additional analyses will evaluate the impact of training with high oxygen delivery on 6-minute walk distance, dyspnea, physical activity, and quality of life. The HOPE-IPF study will lead to a comprehensive understanding of IPF exercise physiology, with the potential to change clinical practice by indicating the need for increased delivery of supplemental oxygen during pulmonary rehabilitation in patients with IPF. Clinical trial registered with www.clinicaltrials.gov (NCT02551068).

Drug delivery vectors based on filamentous bacteriophages and phage-mimetic nanoparticles.

PubMed

Ju, Zhigang; Sun, Wei

2017-11-01

With the development of nanomedicine, a mass of nanocarriers have been exploited and utilized for targeted drug delivery, including liposomes, polymers, nanoparticles, viruses, and stem cells. Due to huge surface bearing capacity and flexible genetic engineering property, filamentous bacteriophage and phage-mimetic nanoparticles are attracting more and more attentions. As a rod-like bio-nanofiber without tropism to mammalian cells, filamentous phage can be easily loaded with drugs and directly delivered to the lesion location. In particular, chemical drugs can be conjugated on phage surface by chemical modification, and gene drugs can also be inserted into the genome of phage by recombinant DNA technology. Meanwhile, specific peptides/proteins displayed on the phage surface are able to conjugate with nanoparticles which will endow them specific-targeting and huge drug-loading capacity. Additionally, phage peptides/proteins can directly self-assemble into phage-mimetic nanoparticles which may be applied for self-navigating drug delivery nanovehicles. In this review, we summarize the production of phage particles, the identification of targeting peptides, and the recent applications of filamentous bacteriophages as well as their protein/peptide for targeting drug delivery in vitro and in vivo. The improvement of our understanding of filamentous bacteriophage and phage-mimetic nanoparticles will supply new tools for biotechnological approaches.

Gene therapy for Parkinson's disease: Disease modification by GDNF family of ligands.

PubMed

Kirik, Deniz; Cederfjäll, Erik; Halliday, Glenda; Petersén, Åsa

2017-01-01

Gene transfer is a promising drug delivery method of advanced therapeutic entities for Parkinson's disease. One advantage over conventional therapies, such as peripheral delivery of the dopamine pre-cursor l-DOPA, is site-specific expression of proteins with regenerative, disease-modifying and potentially neuroprotective capacity. Several clinical trials have been performed to test the capacity of glial-cell line derived neurotrophic factor and neurturin to rescue degenerating dopaminergic neurons in the substantia nigra and their axon terminals in the striatum by delivery of these neurotrophic factors either as purified protein or by means of viral vector mediated gene delivery to the brain. Although gene therapy approaches tested so far have been shown to be safe, none met their primary endpoints in phase II clinical trials designed and powered to test the efficacy of the intervention. Within the scope of this review we aim to describe the state-of-the-art in the field, how different technical parameters were translated from pre-clinical studies in non-human primates to clinical trials, and what these trials taught us regarding important factors that may pave the way to the success of gene therapy for the treatment of Parkinson's disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Implementing antiretroviral therapy programs in resource-constrained settings: lessons from Monze, Zambia.

PubMed

Adedimeji, Adebola; Malokota, Oliver; Manafa, Ogenna

2011-05-01

We describe the impact of an antiretroviral therapy program on human resource utilization and service delivery in a rural hospital in Monze, Zambia, using qualitative data. We assess project impact on staff capacity utilization, service delivery, and community perception of care. Increased workload resulted in fatigue, low staff morale, and exacerbated critical manpower shortages, but also an increase in users of antiretroviral therapy, improvement in hospital infrastructure and funding, and an overall community satisfaction with service delivery. Integrating HAART programs within existing hospital units and services may be a good alternative to increase overall efficiency.

Renewable energy delivery systems and methods

DOEpatents

Walker, Howard Andrew

2013-12-10

A system, method and/or apparatus for the delivery of energy at a site, at least a portion of the energy being delivered by at least one or more of a plurality of renewable energy technologies, the system and method including calculating the load required by the site for the period; calculating the amount of renewable energy for the period, including obtaining a capacity and a percentage of the period for the renewable energy to be delivered; comparing the total load to the renewable energy available; and, implementing one or both of additional and alternative renewable energy sources for delivery of energy to the site.

Approaches to Neural Tissue Engineering Using Scaffolds for Drug Delivery

PubMed Central

Willerth, Stephanie M.; Sakiyama-Elbert, Shelly E.

2007-01-01

This review seeks to give an overview of the current approaches to drug delivery from scaffolds for neural tissue engineering applications. The challenges presented by attempting to replicate the three types of nervous tissue (brain, spinal cord, and peripheral nerve) are summarized. Potential scaffold materials (both synthetic and natural) and target drugs are discussed with the benefits and drawbacks given. Finally, common methods of drug delivery, including degradable/diffusion-based delivery systems, affinity-based delivery systems, immobilized drug delivery systems, and electrically controlled drug delivery systems, are examined and critiqued. Based on the current body of work, suggestions for future directions of research in the field of neural tissue engineering are presented. PMID:17482308

Building capacity in workplace health promotion: the case of the Healthy Together e-learning project.

PubMed

Hodgins, Margaret; Battel-Kirk, Barbara; Asgeirsdottir, Asa G

2010-03-01

The current global economic crisis poses major challenges for workplace health promotion (WHP). Activities that are not perceived to obviously and directly contribute to profits could be sacrificed. This paper argues that WHP must remain centre-stage because of the rights of workers to a healthy, safe working environment but also because of WHP's beneficial financial implications for enterprises. Capacity building for WHP can be developed even within a recessionary environment, particularly if the focus is on the wider workforce, described here as people for whom workplace health promotion may not be their primary function but who have an important role to play in health improvement in workplaces. There is a strong case for the development of the wider workforce based both on the lack of suitably qualified specialists and on the practicalities of having WHP implemented within organizations, particularly for small and medium-sized enterprises (SMEs). SMEs make up a very significant proportion of the global economy and are identified as a priority area for action internationally. An example of an e-learning course, the Healthy Together programme, developed by a partnership of three countries, is discussed as an approach that has potential to develop capacity for WHP in the current climate. The findings of the evaluation of the Healthy Together programme indicate that there is a real potential in developing e-learning materials for training those with a brief for promoting workplace health and safety in SMEs. Although modifications in some aspects of delivery identified in the evaluation of the pilot course need to be considered, the course was well received, and was reported to be relevant to the learning needs of students, to their workplaces and specifically to small businesses in rural areas. Specific features of the e-learning approach increase its potential to address capacity building for WHP.

Bioaccessibility of hydroxytyrosol and n-3 fatty acids as affected by the delivery system: simple, double and gelled double emulsions.

PubMed

Cofrades, Susana; Bou, Ricard; Flaiz, Linda; Garcimartín, Alba; Benedí, Juana; Mateos, Raquel; Sánchez-Muniz, Francisco J; Olivero-David, Raúl; Jiménez-Colmenero, Francisco

2017-06-01

This study examines the influence of different food-grade n-3 PUFA-enriched simple emulsion (SE), double emulsion (DE) and gelled double emulsion (GDE) delivery systems on the extent of lipolysis, antioxidant capacity and the bioaccessibility of hydroxytyrosol (HTy). GDE emulsion offered better protection for HTy (89%) than the other systems (79% in SE and DE). The reducing capacity of the emulsions containing HTy were not altered during oral digestion. However, "in vitro" gastric and intestinal phases significantly reduced the antioxidant activity of all systems. The structural and physical state of GDE entailed a slowing-down of triacylglyceride hydrolysis (36.4%) in comparison with that of SE and DE (22.7 and 24.8% for SE and DE, respectively).

A novel local anesthetic system: transcriptional transactivator peptide-decorated nanocarriers for skin delivery of ropivacaine.

PubMed

Chen, Chuanyu; You, Peijun

2017-01-01

Barrier properties of the skin and physicochemical properties of drugs are the main factors for the delivery of local anesthetic molecules. The present work evaluates the anesthetic efficacy of drug-loaded nanocarrier (NC) systems for the delivery of local anesthetic drug, ropivacaine (RVC). In this study, transcriptional transactivator peptide (TAT)-decorated RVC-loaded NCs (TAT-RVC/NCs) were successfully fabricated. Physicochemical properties of NCs were determined in terms of particle size, zeta potential, drug encapsulation efficiency, drug-loading capacity, stability, and in vitro drug release. The skin permeation of NCs was examined using a Franz diffusion cell mounted with depilated mouse skin in vitro, and in vivo anesthetic effect was evaluated in mice. The results showed that TAT-RVC/NCs have a mean diameter of 133.2 nm and high drug-loading capacity of 81.7%. From the in vitro skin permeation results, it was observed that transdermal flux of TAT-RVC/NCs was higher than that of RVC-loaded NCs (RVC/NCs) and RVC injection. The evaluation of in vivo anesthetic effect illustrated that TAT-RVC/NCs can enhance the transdermal delivery of RVC by reducing the pain threshold in mice. These results indicate that TAT-decorated NCs systems are useful for overcoming the barrier function of the skin, decreasing the dosage of RVC and enhancing the anesthetic effect. Therefore, TAT-decorated NCs can be used as an effective transdermal delivery system for local anesthesia.

Additive solution-7 reduces the red blood cell cold storage lesion.

PubMed

Cancelas, Jose A; Dumont, Larry J; Maes, Lou A; Rugg, Neeta; Herschel, Louise; Whitley, Pamela H; Szczepiokowski, Zbigniew M; Siegel, Alan H; Hess, John R; Zia, Majid

2015-03-01

Transfusion of long-stored red blood cells (RBCs) is associated with decreased in vivo RBC recovery, delivery of RBC breakdown products, and increased morbidity and mortality. Reducing the burden of this RBC "storage lesion" is a major challenge in transfusion medicine. Additive solution-7 (AS-7) is a new RBC storage solution designed to improve RBC metabolism by providing phosphate and increasing buffering capacity. Storage quality in AS-7 was measured in a prospective, randomized, three-center trial using units of whole blood from healthy human subjects whose RBCs were stored for up to 56 days in AS-7 (n = 120) or for 42 days in the control solution AS-1 (n = 60). Hemolysis and shedding of protein-containing microvesicles were significantly reduced in RBCs stored in AS-7 for 42 and 56 days compared with RBCs stored in AS-1. Autologous in vivo recoveries of RBCs stored in AS-7 was 88 ± 5% at 42 days (n = 27) and 82 ± 3% at 56 days (n = 27), exceeding recoveries of RBCs stored in currently used solutions. Increasing the phosphate, pH range, and buffer capacity of a RBC storage system allowed RBCs to be stored better and longer than currently approved storage systems. AS-7 ameliorates the long-term storage lesion resulting in significantly increased viability in vitro and in vivo. © 2014 AABB.

Describing the primary care system capacity for the prevention and management of non-communicable diseases in rural Vietnam.

PubMed

Van Minh, Hoang; Do, Young Kyung; Bautista, Mary Ann Cruz; Tuan Anh, Tran

2014-01-01

The primary care system in Vietnam has been shown to play a crucial role in disease prevention and health promotion. This study described the primary care system in a selected rural area in Vietnam in terms of its capacity for prevention and control of non-communicable diseases (NCDs). The study was conducted in 2011 in Dong Hy district, Thai Nguyen province-a rural community located in northern Vietnam. Mixed methods were used, including quantitative and qualitative and literature review approaches, to collect data on the current status of the six building blocks of the primary care system in Dong Hy district. Selected health workers and stakeholders in the selected healthcare facilities were surveyed. A description of Dong Hy district's primary care capacity for NCD prevention and control is reported. (i) Service delivery: The current practice in NCD prevention and treatment is mainly based on a single risk factor rather than a combination of cardiovascular disease risks. (ii) Governance: At the primary care level, multi-sectoral collaborations are limited, and there is insufficient integration of NCD preventive activities. (iii) Financing: A national budget for NCD prevention and control is lacking. The cost of treatment and medicines is high, whereas the health insurance scheme limits the list of available medicines and the reimbursement ceiling level. Health workers have low remuneration despite their important roles in NCD prevention. (iv) Human resources: The quantity and quality of health staff working at the primary care level, especially those in preventive medicine, are insufficient. (v) Information and research: The health information system in the district is weak, and there is no specific information system for collecting population-based NCD data. (vi) Medical products and technology: Not all essential equipment and medicines recommended by the WHO are always available at the commune health centre. The capacity of the primary care system in Vietnam is still inadequate to serve the NCD-related health needs of the population. There is an urgent need to improve the primary care capacity for NCD prevention and management in Vietnam. Copyright © 2013 John Wiley & Sons, Ltd.

Application of three-dimensional printing for colon targeted drug delivery systems

PubMed Central

Charbe, Nitin B.; McCarron, Paul A.; Lane, Majella E.; Tambuwala, Murtaza M.

2017-01-01

Orally administered solid dosage forms currently dominate over all other dosage forms and routes of administrations. However, human gastrointestinal tract (GIT) poses a number of obstacles to delivery of the drugs to the site of interest and absorption in the GIT. Pharmaceutical scientists worldwide have been interested in colon drug delivery for several decades, not only for the delivery of the drugs for the treatment of colonic diseases such as ulcerative colitis and colon cancer but also for delivery of therapeutic proteins and peptides for systemic absorption. Despite extensive research in the area of colon targeted drug delivery, we have not been able to come up with an effective way of delivering drugs to the colon. The current tablets designed for colon drug release depend on either pH-dependent or time-delayed release formulations. During ulcerative colitis the gastric transit time and colon pH-levels is constantly changing depending on whether the patient is having a relapse or under remission. Hence, the current drug delivery system to the colon is based on one-size-fits-all. Fails to effectively deliver the drugs locally to the colon for colonic diseases and delivery of therapeutic proteins and peptides for systemic absorption from the colon. Hence, to overcome the current issues associated with colon drug delivery, we need to provide the patients with personalized tablets which are specifically designed to match the individual's gastric transit time depending on the disease state. Three-dimensional (3D) printing (3DP) technology is getting cheaper by the day and bespoke manufacturing of 3D-printed tablets could provide the solutions in the form of personalized colon drug delivery system. This review provides a bird's eye view of applications and current advances in pharmaceutical 3DP with emphasis on the development of colon targeted drug delivery systems. PMID:28929046

Application of three-dimensional printing for colon targeted drug delivery systems.

PubMed

Charbe, Nitin B; McCarron, Paul A; Lane, Majella E; Tambuwala, Murtaza M

2017-01-01

Orally administered solid dosage forms currently dominate over all other dosage forms and routes of administrations. However, human gastrointestinal tract (GIT) poses a number of obstacles to delivery of the drugs to the site of interest and absorption in the GIT. Pharmaceutical scientists worldwide have been interested in colon drug delivery for several decades, not only for the delivery of the drugs for the treatment of colonic diseases such as ulcerative colitis and colon cancer but also for delivery of therapeutic proteins and peptides for systemic absorption. Despite extensive research in the area of colon targeted drug delivery, we have not been able to come up with an effective way of delivering drugs to the colon. The current tablets designed for colon drug release depend on either pH-dependent or time-delayed release formulations. During ulcerative colitis the gastric transit time and colon pH-levels is constantly changing depending on whether the patient is having a relapse or under remission. Hence, the current drug delivery system to the colon is based on one-size-fits-all. Fails to effectively deliver the drugs locally to the colon for colonic diseases and delivery of therapeutic proteins and peptides for systemic absorption from the colon. Hence, to overcome the current issues associated with colon drug delivery, we need to provide the patients with personalized tablets which are specifically designed to match the individual's gastric transit time depending on the disease state. Three-dimensional (3D) printing (3DP) technology is getting cheaper by the day and bespoke manufacturing of 3D-printed tablets could provide the solutions in the form of personalized colon drug delivery system. This review provides a bird's eye view of applications and current advances in pharmaceutical 3DP with emphasis on the development of colon targeted drug delivery systems.

Influence of cationic lipid concentration on properties of lipid-polymer hybrid nanospheres for gene delivery.

PubMed

Bose, Rajendran J C; Arai, Yoshie; Ahn, Jong Chan; Park, Hansoo; Lee, Soo-Hong

2015-01-01

Nanoparticles have been widely used for nonviral gene delivery. Recently, cationic hybrid nanoparticles consisting of two different materials were suggested as a promising delivery vehicle. In this study, nanospheres with a poly(D,L-lactic-co-glycolic acid) (PLGA) core and cationic lipid shell were prepared, and the effect of cationic lipid concentrations on the properties of lipid polymer hybrid nanocarriers investigated. Lipid-polymer hybrid nanospheres (LPHNSs) were fabricated by the emulsion-solvent evaporation method using different concentrations of cationic lipids and characterized for size, surface charge, stability, plasmid DNA-binding capacity, cytotoxicity, and transfection efficiency. All LPHNSs had narrow size distribution with positive surface charges (ζ-potential 52-60 mV), and showed excellent plasmid DNA-binding capacity. In vitro cytotoxicity measurements with HEK293T, HeLa, HaCaT, and HepG2 cells also showed that LPHNSs exhibited less cytotoxicity than conventional transfection agents, such as Lipofectamine and polyethyleneimine-PLGA. As cationic lipid concentrations increased, the particle size of LPHNSs decreased while their ζ-potential increased. In addition, the in vitro transfection efficiency of LPHNSs increased as lipid concentration increased.

Vaccine vial stopper performance for fractional dose delivery of vaccines

PubMed Central

Jarrahian, Courtney; Myers, Daniel; Creelman, Ben; Saxon, Eugene; Zehrung, Darin

2017-01-01

ABSTRACT Shortages of vaccines such as inactivated poliovirus and yellow fever vaccines have been addressed by administering reduced—or fractional—doses, as recommended by the World Health Organization Strategic Advisory Group of Experts on Immunization, to expand population coverage in countries at risk. We evaluated 3 kinds of vaccine vial stoppers to assess their performance after increased piercing from repeated withdrawal of doses needed when using fractional doses (0.1 mL) from presentations intended for full-dose (0.5 mL) delivery. Self-sealing capacity and fragmentation of the stopper were assessed via modified versions of international standard protocols. All stoppers maintained self-sealing capacity after 100 punctures. The damage to stoppers measured as the fragmentation rate was within the target of ≤ 10% of punctures resulting in a fragment after as many as 50 punctures. We concluded that stopper failure is not likely to be a concern if existing vaccine vials containing up to 10 regular doses are used up to 50 times for fractional dose delivery. PMID:28463054

Pharmaceutical liposomal drug delivery: a review of new delivery systems and a look at the regulatory landscape.

PubMed

Zylberberg, Claudia; Matosevic, Sandro

2016-11-01

Liposomes were the first nanoscale drug to be approved for clinical use in 1995. Since then, the technology has grown considerably, and pioneering recent work in liposome-based delivery systems has brought about remarkable developments with significant clinical implications. This includes long-circulating liposomes, stimuli-responsive liposomes, nebulized liposomes, elastic liposomes for topical, oral and transdermal delivery and covalent lipid-drug complexes for improved drug plasma membrane crossing and targeting to specific organelles. While the regulatory bodies' opinion on liposomes is well-documented, current guidance that address new delivery systems are not. This review describes, in depth, the current state-of-the-art of these new liposomal delivery systems and provides a critical overview of the current regulatory landscape surrounding commercialization efforts of higher-level complexity systems, the expected requirements and the hurdles faced by companies seeking to bring novel liposome-based systems for clinical use to market.

Uptake and transfection with polymeric nanoparticles are dependent on polymer end-group structure, but largely independent of nanoparticle physical and chemical properties

PubMed Central

Sunshine, Joel C.; Peng, Daniel Y.; Green, Jordan J.

2012-01-01

Development of non-viral particles for gene delivery requires a greater understanding of the properties that enable gene delivery particles to overcome the numerous barriers to intracellular DNA delivery. Linear poly(beta-amino) esters (PBAE) have shown substantial promise for gene delivery, but the mechanism behind their effectiveness is not well quantified with respect to these barriers. In this study, we synthesized, characterized, and evaluated for gene delivery an array of linear PBAEs that differed by small changes along the backbone, side chain, and end-group of the polymers. We examined particle size and surface charge, polymer molecular weight, polymer degradation rate, buffering capacity, cellular uptake, transfection, and cytotoxicity of nanoparticles formulated with these polymers. Significantly, this is the first study that has quantified how small differential structural changes to polymers of this class modulate buffering capacity and polymer degradation rate and relates these findings to gene delivery efficacy. All polymers formed positively charged (zeta potential 21–29 mV) nanosized articles (~ 150 nm). The polymers hydrolytically degraded quickly in physiological conditions, with half-lives ranging from 90 minutes to 6 hours depending on polymer structure. The PBAE buffering capacities in the relevant pH range (pH 5.1 – 7.4) varied from 34% to 95% protonable amines, and on a per mass basis, PBAEs buffered 1.4–4.6 mmol H+/g. When compared to 25 kDa branched polyethyleneimine (PEI), PBAEs buffer significantly fewer protons/mass, as PEI buffers 6.2 mmol H+/g over the same range. However, due to the relatively low cytotoxicity of PBAEs, higher polymer mass can be used to form particles than with PEI and total buffering capacity of PBAE-based particles significantly exceeds that of PEI. Uptake into COS-7 cells ranged from 0% to 95% of cells and transfection ranged from 0% to 93% of cells, depending on the base polymer structure and the end-modifications examined. Five polymers achieved higher uptake and transfection efficacy with less toxicity than branched-PEI control. Surprisingly, acrylate-terminated base polymers were dramatically less efficacious than their end-capped versions, both in terms of uptake (1–3% for acrylate, 75–94% for end-capped) and transfection efficacy (0–1% vs. 20–89%), even though there are minimal differences between acrylate and end-capped polymers in terms of DNA retardation in gel electrophoresis, particle size, zeta potential, and cytotoxicity. These studies further elucidate the role of polymer structure for gene delivery and highlight that small molecule end-group modification of a linear polymer can be critical for cellular uptake in a manner that is largely independent of polymer/DNA binding, particle size, and particle surface charge. PMID:22970908

Highly efficient siRNA delivery from core-shell mesoporous silica nanoparticles with multifunctional polymer caps

NASA Astrophysics Data System (ADS)

Möller, Karin; Müller, Katharina; Engelke, Hanna; Bräuchle, Christoph; Wagner, Ernst; Bein, Thomas

2016-02-01

A new general route for siRNA delivery is presented combining porous core-shell silica nanocarriers with a modularly designed multifunctional block copolymer. Specifically, the internal storage and release of siRNA from mesoporous silica nanoparticles (MSN) with orthogonal core-shell surface chemistry was investigated as a function of pore-size, pore morphology, surface properties and pH. Very high siRNA loading capacities of up to 380 μg per mg MSN were obtained with charge-matched amino-functionalized mesoporous cores, and release profiles show up to 80% siRNA elution after 24 h. We demonstrate that adsorption and desorption of siRNA is mainly driven by electrostatic interactions, which allow for high loading capacities even in medium-sized mesopores with pore diameters down to 4 nm in a stellate pore morphology. The negatively charged MSN shell enabled the association with a block copolymer containing positively charged artificial amino acids and oleic acid blocks, which acts simultaneously as capping and endosomal release agent. The potential of this multifunctional delivery platform is demonstrated by highly effective cell transfection and siRNA delivery into KB-cells. A luciferase reporter gene knock-down of up to 80-90% was possible using extremely low cell exposures with only 2.5 μg MSN containing 0.5 μg siRNA per 100 μL well.A new general route for siRNA delivery is presented combining porous core-shell silica nanocarriers with a modularly designed multifunctional block copolymer. Specifically, the internal storage and release of siRNA from mesoporous silica nanoparticles (MSN) with orthogonal core-shell surface chemistry was investigated as a function of pore-size, pore morphology, surface properties and pH. Very high siRNA loading capacities of up to 380 μg per mg MSN were obtained with charge-matched amino-functionalized mesoporous cores, and release profiles show up to 80% siRNA elution after 24 h. We demonstrate that adsorption and desorption of siRNA is mainly driven by electrostatic interactions, which allow for high loading capacities even in medium-sized mesopores with pore diameters down to 4 nm in a stellate pore morphology. The negatively charged MSN shell enabled the association with a block copolymer containing positively charged artificial amino acids and oleic acid blocks, which acts simultaneously as capping and endosomal release agent. The potential of this multifunctional delivery platform is demonstrated by highly effective cell transfection and siRNA delivery into KB-cells. A luciferase reporter gene knock-down of up to 80-90% was possible using extremely low cell exposures with only 2.5 μg MSN containing 0.5 μg siRNA per 100 μL well. Electronic supplementary information (ESI) available: MSN synthesis and analysis, sample preparation for cell transfections as well as additional studies including experiments with a second cell line and a toxicity assay. See DOI: 10.1039/c5nr06246b

Current Faculty Development Practices for Alternative Delivery Systems in Christian Higher Education Institutions: A Qualitative Study

ERIC Educational Resources Information Center

Yates, Steven Lowell

2009-01-01

This research study was an investigation of current faculty development practices for alternative delivery systems. Attention was given to faculty development in general as well as specific facets of faculty development for alternative delivery systems. Future or intended faculty development practices were pursued, along with factors that…

Chitosan-coated boron nitride nanospheres enhance delivery of CpG oligodeoxynucleotides and induction of cytokines

PubMed Central

Zhang, Huijie; Chen, Song; Zhi, Chunyi; Yamazaki, Tomohiko; Hanagata, Nobutaka

2013-01-01

Background Cytosine-phosphate-guanine (CpG) oligodeoxynucleotides activate Toll-like receptor 9, leading to induction of proinflammatory cytokines, which play an important role in induction and maintenance of innate and adaptive immune responses. Previously, we have used boron nitride nanospheres (BNNS) as a carrier for delivery of unmodified CpG oligodeoxynucleotides to activate Toll-like receptor 9. However, because CpG oligodeoxynucleotides and BNNS are both negatively charged, electrostatic repulsion between them is likely to reduce the loading of CpG oligodeoxynucleotides onto BNNS. Therefore, the efficiency of uptake of CpG oligodeoxynucleotides is also limited and does not result in induction of a robust cytokine response. To ameliorate these problems, we developed a CpG oligodeoxynucleotide delivery system using chitosan-coated BNNS as a carrier. Methods To facilitate attachment of CpG oligodeoxynucleotides onto the BNNS and improve their loading capacity, we prepared positively charged BNNS by coating them with chitosan preparations of three different molecular weights and used them as carriers for delivery of CpG oligodeoxynucleotides. Results The zeta potentials of the BNNS-CS complexes were positive, and chitosan coating improved their dispersity and stability in aqueous solution compared with BNNS. The positive charge of the BNNS-CS complexes greatly improved the loading capacity and cellular uptake efficiency of CpG oligodeoxynucleotides. The loading capacity of the CpG oligodeoxynucleotides depended on the molecular weight of chitosan, which affected the positive charge density on the surface of the BNNS. CpG oligodeoxynucleotides loaded onto BNNS-CS complexes significantly enhanced production of interleukin-6 and tumor necrosis factor-α by peripheral blood mononuclear cells compared with CpG oligodeoxynucleotides directly loaded onto BNNS, or when Lipofectamine™ 2000 was used as the carrier. The molecular weight of the chitosan used to coat the BNNS affected the magnitude of cytokine induction by varying the strength of condensation of the CpG oligodeoxynucleotides. Conclusion Although the loading capacity of BNNS coated with low molecular weight chitosan preparations was the lowest of all the preparations, they induced the highest levels of cytokines. PMID:23674892

HIV vaccines: current challenges and future directions.

PubMed

Avrett, Sam; Collins, Chris

2002-07-01

Volume seven of the Review will mark the tenth anniversary of the Canadian HIV/AIDS Legal Network with a series of articles that describe past developments and future directions in several areas of policy and law related to HIV/AIDS. The following article is the first of these, discussing current challenges and future directions in the development of and access to HIV vaccines. It argues that governments are under public health, ethical, and legal obligations to develop and provide access to HIV vaccines. It further explains what is required for governments to fulfill their obligations: additional commitment and resources for HIV vaccine development in the context of increased global research and development regarding diseases of the poor; increased support and advocacy for partnerships to develop HIV vaccines; enhanced regulatory capacity in every country to review, approve, and monitor HIV vaccines; and assurance of global supply of, procurement of, delivery of, and access to vaccines in the context of efforts to increase global access to public health measures and technologies.

The state of human dimensions capacity for natural resource management: needs, knowledge, and resources

USGS Publications Warehouse

Sexton, Natalie R.; Leong, Kirsten M.; Milley, Brad J.; Clarke, Melinda M.; Teel, Tara L.; Chase, Mark A.; Dietsch, Alia M.

2013-01-01

The social sciences have become increasingly important in understanding natural resource management contexts and audiences, and are essential in design and delivery of effective and durable management strategies. Yet many agencies and organizations do not have the necessary resource management. We draw on the textbook definition of HD: how and why people value natural resources, what benefits people seek and derive from those resources, and how people affect and are affected by those resources and their management (Decker, Brown, and Seimer 2001). Clearly articulating how HD information can be used and integrated into natural resource management planning and decision-making is an important challenge faced by the HD field. To address this challenge, we formed a collaborative team to explore the issue of HD capacity-building for natural resource organizations and to advance the HD field. We define HD capacity as activities, efforts, and resources that enhance the ability of HD researchers and practitioners and natural managers and decision-makers to understand and address the social aspects of conservation.Specifically, we sought to examine current barriers to integration of HD into natural resource management, knowledge needed to improve HD capacity, and existing HD tools, resources, and training opportunities. We conducted a needs assessment of HD experts and practitioners, developed a framework for considering HD activities that can contribute both directly and indirectly throughout any phase of an adaptive management cycle, and held a workshop to review preliminary findings and gather additional input through breakout group discussions. This paper provides highlights from our collaborative initiative to help frame and inform future HD capacity-building efforts and natural resource organizations and also provides a list of existing human dimensions tools and resources.

The Loneliness of the Long-Distance Learner: Social Networking and Student Support. A Case Study of the Distance-Learning MA in Translation at Bristol University

ERIC Educational Resources Information Center

Duranton, Helene; Mason, Adrienne

2012-01-01

Using the translation programme at the University of Bristol as a case study, we shall argue in this paper that distance delivery can have a very positive impact on recruitment but that the quality of the students' experience depends upon the capacity of the organisation to support course development and delivery, both in terms of instructional…

Propylene glycol-embodying deformable liposomes as a novel drug delivery carrier for vaginal fibrauretine delivery applications.

PubMed

Li, Wei-Ze; Hao, Xu-Liang; Zhao, Ning; Han, Wen-Xia; Zhai, Xi-Feng; Zhao, Qian; Wang, Yu-E; Zhou, Yong-Qiang; Cheng, Yu-Chuan; Yue, Yong-Hua; Fu, Li-Na; Zhou, Ji-Lei; Wu, Hong-Yu; Dong, Chun-Jing

2016-03-28

The purpose of this work was to develop and characterize the fibrauretine (FN) loaded propylene glycol-embodying deformable liposomes (FDL), and evaluate the pharmacokinetic behavior and safety of FDL for vaginal drug delivery applications. FDL was characterized for structure, particle size, zeta potential, deformability and encapsulation efficiency; the ability of FDL to deliver FN across vagina tissue in vitro and the distribution behavior of FN in rat by vaginal drug delivery were investigated, the safety of FDL to the vagina of rabbits and rats as well as human vaginal epithelial cells (VK2/E6E7) were also evaluated. Results revealed that: (i) the FDL have a closed spherical shape and lamellar structure with a homogeneous size of 185±19nm, and exhibited a negative charge of -53±2.7mV, FDL also have a good flexibility with a deformability of 92±5.6 (%phospholipids/min); (ii) the dissolving capacity of inner water phase and hydrophilicity of phospholipid bilayers of deformable liposomes were increased by the presence of propylene glycol, this may be elucidated by the fluorescent probes both lipophilic Nile red and hydrophilic calcein that were filled up the entire volume of the FDL uniformly, so the FDL with a high entrapment capacity (were calculated as percentages of total drug) for FN was 78±2.14%; (iii) the permeability of FN through vaginal mucosa was obviously improved by propylene glycol-embodying deformable liposomes, no matter whether the FN loaded in liposomes or not, although FN loaded in liposomes caused the highest permeability and drug reservoir in vagina; (iv) the FN mainly aggregated in the vagina and uterus, then the blood, spleen, liver, kidney, heart and lungs for vaginal drug delivery, this indicating vaginal delivery of FDL have a better 'vaginal local targeting effect'; and (v) the results of safety evaluation illustrate that the FDL is non-irritant and well tolerated in vivo, thereby establishing its vaginal drug delivery potential. These results indicate that the propylene glycol-embodying deformable liposomes may be a promising drug delivery carrier for vaginal delivery of fibrauretine. Copyright © 2016 Elsevier B.V. All rights reserved.

TH-AB-BRB-01: Trajectory Modulated Arc Therapy: Application to Partial Breast Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hristov, D.

2016-06-15

Current state-of-the art digital C-arm medical linear accelerators are capable of delivering radiation treatments with high level of automation, which affords coordinated motions of gantry, couch, and multileaf collimator (MLC) with dose rate modulations. The new machine capacity has shown the potential to bring substantially improved radiation dosimetry and/or delivery efficiency to many challenging diseases. Combining an integrated beam orientation optimization algorithm with automated machine navigation, markedly improved dose conformity has been achieved using 4ρ therapy. Trajectory modulated radiation therapy (TMAT) can be used to deliver highly conformal dose to partial breast or to carve complex dose distribution for therapymore » involving extended volumes such as total marrow and total lymph node treatment. Dynamic electron arc radiotherapy (DEAR) not only overcomes the deficiencies of conventional electron therapy in dose conformity and homogeneity but also achieves so without patient-specific shields. The combination of MLC and couch tracking provides improved motion management of thoracic and abdominal tumors. A substantial body of work has been done in these technological advances for clinical translation. The proposed symposium will provide a timely review of these exciting opportunities. Learning Objectives: Recognize the potential of using digitally controlled linacs for clinically significant improvements in delivered dose distributions for various treatment sites. Identify existing approaches to treatment planning, optimization and delivery for treatment techniques utilizing the advanced functions of digital linacs and venues for further development and improvement. Understand methods for testing and validating delivery system performance. Identify tools available on current delivery systems for implementation and control for such treatments. Obtain the update in clinical applications, trials and regulatory approval. K. Sheng, NIH U19AI067769, NIH R43CA183390, NIH R01CA188300, Varian Medical Systems V. Yu, Varian Medical Systems, AAPM Summer Undergraduate Fellowship, NSF graduate fellowship S. Nill, Elekta AB. Cancer Research UK under Programme C33589/A19727, NIHR Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research.« less

Need for generic, innovative and geometric deliveries in developing self-sustaining capacity building in remote sensing

NASA Astrophysics Data System (ADS)

Gupta, R. K.; Balamanikavelu, P. M.; Vijayan, D.; Prasad, T. S.

Everybody uses a bulb to illustrate an idea but nobody shows where the current comes from. Majority of remote sensing user community comes from natural and social sciences domain while remote sensing technology evolves from physical and engineering sciences. To ensure inculcation and internalization of remote sensing technology by application/resource scientists, trainer needs to transfer physical and engineering concepts in geometric manner. Here, the steering for the transfer of knowledge (facts, procedures, concepts and principles) and skills (thinking, acting, reacting and interacting) needs to take the trainees from Known to Unknown, Concrete to Abstract, Observation to Theory and Simple to Complex. In the initial stage of training/education, experiential learning by instructor led exploring of thematic details in false colour composite (FCC) as well as in individual black and white spectral band(s) imagery by trainees not only creates interest, confidence build-up and orientation towards purposeful learning but also helps them to overcome their inhibitions towards the physical and engineering basal. The methodology to be adopted has to inculcate productive learning, emphasizing more on thinking and trial and error aspects as opposed to reproductive learning based dominantly on being told and imitation. The delivery by trainer needs to ensure dynamic, stimulating and effective discussions through deluging questions pertaining to analysis, synthesis and evaluation nature. This would ensure proactive participation from trainees. Hands-on module leads to creative concretization of concepts. To keep the trainees inspired to learn in an auto mode during post-training period, they need to consciously swim in the current and emerging knowledge pool during training programme. This is achieved through assignment of seminar delivery task to the trainees. During the delivery of seminar, peers and co-trainees drive the trainee to communicate the seminar content not only in what but also in how and why mode. The interest culminated in this manner keeps the entropy of the trainee minimized even during post-training professional life. So, such germinated trainee would always generate positive induction among colleagues; thus, helping in realising multiplier effect.

Towards a new paradigm for innovative training methods for capacity building in remote sensing

NASA Astrophysics Data System (ADS)

Gupta, R. K.; Manikavelu, P. M. Bala; Vijayan, D.; Prasad, T. S.

2006-01-01

Everybody uses a bulb to illustrate an idea but nobody shows where the current comes from. Majority of remote sensing user community comes from natural and social sciences domain while remote sensing technology evolves from physical and engineering sciences. To ensure inculcation and internalization of remote sensing technology by application/resource scientists, trainer needs to transfer physical and engineering concepts in geometric manner. Here, the steering for the transfer of knowledge (facts, procedures, concepts and principles) and skills (thinking, acting, reacting and interacting) needs to take the trainees from Known to Unknown, Concrete to Abstract, Observation to Theory and Simple to Complex. In the initial stage of training/education, experiential learning by instructor led exploring of thematic details in false colour composite (FCC) as well as in individual black and white spectral band(s) imagery by trainees not only creates interest, confidence build-up and orientation towards purposeful learning but also helps them to overcome their inhibitions towards the physical and engineering basal. The methodology to be adopted has to inculcate productive learning, emphasizing more on thinking and trial and error aspects as opposed to reproductive learning based dominantly on being told and imitation. The delivery by trainer needs to ensure dynamic, stimulating and effective discussions through deluging questions pertaining to analysis, synthesis and evaluation nature. This would ensure proactive participation from trainees. Hands-on module leads to creative concretization of concepts. To keep the trainees inspired to learn in an auto mode during post-training period, they need to consciously swim in the current and emerging knowledge pool during training programme. This is achieved through assignment of seminar delivery task to the trainees. During the delivery of seminar, peers and co-trainees drive the trainee to communicate the seminar content not only in what but also in how and why mode. The interest culminated in this manner keeps the entropy of the trainee minimized even during post-training professional life. So, such germinated trainee would always generate positive induction among colleagues; thus, helping in realizing multiplier effect. Based upon above thought process(es), the paper discusses the concept of "thinking curricula" and associated cares needed in training deliveries.

Dynamic Routing for Delay-Tolerant Networking in Space Flight Operations

NASA Technical Reports Server (NTRS)

Burleigh, Scott C.

2008-01-01

Contact Graph Routing (CGR) is a dynamic routing system that computes routes through a time-varying topology composed of scheduled, bounded communication contacts in a network built on the Delay-Tolerant Networking (DTN) architecture. It is designed to support operations in a space network based on DTN, but it also could be used in terrestrial applications where operation according to a predefined schedule is preferable to opportunistic communication, as in a low-power sensor network. This paper will describe the operation of the CGR system and explain how it can enable data delivery over scheduled transmission opportunities, fully utilizing the available transmission capacity, without knowing the current state of any bundle protocol node (other than the local node itself) and without exhausting processing resources at any bundle router.

The African Field Epidemiology Network-Networking for effective field epidemiology capacity building and service delivery

PubMed Central

Gitta, Sheba Nakacubo; Mukanga, David; Babirye, Rebecca; Dahlke, Melissa; Tshimanga, Mufuta; Nsubuga, Peter

2011-01-01

Networks are a catalyst for promoting common goals and objectives of their membership. Public Health networks in Africa are crucial, because of the severe resource limitations that nations face in dealing with priority public health problems. For a long time, networks have existed on the continent and globally, but many of these are disease-specific with a narrow scope. The African Field Epidemiology Network (AFENET) is a public health network established in 2005 as a non-profit networking alliance of Field Epidemiology and Laboratory Training Programs (FELTPs) and Field Epidemiology Training Programs (FETPs) in Africa. AFENET is dedicated to helping ministries of health in Africa build strong, effective and sustainable programs and capacity to improve public health systems by partnering with global public health experts. The Network's goal is to strengthen field epidemiology and public health laboratory capacity to contribute effectively to addressing epidemics and other major public health problems in Africa. AFENET currently networks 12 FELTPs and FETPs in sub-Saharan Africa with operations in 20 countries. AFENET has a unique tripartite working relationship with government technocrats from human health and animal sectors, academicians from partner universities, and development partners, presenting the Network with a distinct vantage point. Through the Network, African nations are making strides in strengthening their health systems. Members are able to: leverage resources to support field epidemiology and public health laboratory training and service delivery notably in the area of outbreak investigation and response as well as disease surveillance; by-pass government bureaucracies that often hinder and frustrate development partners; and consolidate efforts of different partners channelled through the FELTPs by networking graduates through alumni associations and calling on them to offer technical support in various public health capacities as the need arises. AFENET presents a bridging platform between governments and the private sector, allowing for continuity of health interventions at the national and regional level while offering free exit and entry for existing and new partners respectively. AFENET has established itself as a versatile networking model that is highly responsive to members’ needs. Based on the successes recorded in AFENET's first 5 years, we envision that the Network's membership will continue to expand as new training programs are established. The lessons learned will be useful in initiating new programs and building sustainability frameworks for FETPs and FELTPs in Africa. AFENET will continue to play a role in coordinating, advocacy, and building capacity for epidemic disease preparedness and response. PMID:22359691

Self-assembled magnetic theranostic nanoparticles for highly sensitive MRI of minicircle DNA delivery.

PubMed

Wan, Qian; Xie, Lisi; Gao, Lin; Wang, Zhiyong; Nan, Xiang; Lei, Hulong; Long, Xiaojing; Chen, Zhi-Ying; He, Cheng-Yi; Liu, Gang; Liu, Xin; Qiu, Bensheng

2013-01-21

As a versatile gene vector, minicircle DNA (mcDNA) has a great potential for gene therapy. However, some serious challenges remain, such as to effectively deliver mcDNA into targeted cells/tissues and to non-invasively monitor the delivery of the mcDNA. Superparamagnetic iron oxide (SPIO) nanoparticles have been extensively used for both drug/gene delivery and diagnosis. In this study, an MRI visible gene delivery system was developed with a core of SPIO nanocrystals and a shell of biodegradable stearic acid-modified low molecular weight polyethyleneimine (Stearic-LWPEI) via self-assembly. The Stearic-LWPEI-SPIO nanoparticles possess a controlled clustering structure, narrow size distribution and ultrasensitive imaging capacity. Furthermore, the nanoparticle can effectively bind with mcDNA and protect it from enzymatic degradation. In conclusion, the nanoparticle shows synergistic advantages in the effective transfection of mcDNA and non-invasive MRI of gene delivery.

Electrostatic wrapping of doxorubicin with curdlan to construct an efficient pH-responsive drug delivery system

NASA Astrophysics Data System (ADS)

Zhou, Jiang-Ling; Song, Fei; Tian, Jia-Feng; Nie, Wu-Cheng; Wang, Xiu-Li; Wang, Yu-Zhong

2017-07-01

The development of environmentally responsive drug delivery systems for the treatment of cancer has attracted particular interest in recent years. However, the enhancement of drug loading capacity and realization of pH-responsive drug delivery remain challenging. Herein, we employ carboxymethyl curdlan as a hydrophilic carrier to wrap doxorubicin (DOX) directly via electrostatic interaction. The sizes of the formed nanoparticles can be simply tuned by changing their feeding ratios. In particular, the nanoparticles are highly stable in aqueous solution without size variation. In vitro drug release and cytotoxicity assays illustrate that this delivery system can release DOX differentially under various environmental conditions and transport it into cell nuclei efficiently, with comparable therapeutic effect to the free drug. These results suggest that the carrying of antitumor drugs by polysaccharide via electrostatic interaction is a simple but effective way to construct a pH-dependent drug delivery platform.

A Promising Combo Gene Delivery System Developed from (3-Aminopropyl)triethoxysilane-Modified Iron Oxide Nanoparticles and Cationic Polymers

NASA Astrophysics Data System (ADS)

Zhang, Zubin; Song, Lina; Dong, Jinlai; Guo, Dawei; Du, Xiaolin; Cao, Biyin; Zhang, Yu; Gu, Ning; Mao, Xinliang

2013-05-01

(3-Aminopropyl)triethoxysilane-modified iron oxide nanoparticles (APTES-IONPs) have been evaluated for various biomedical applications, including medical imaging and drug delivery. Cationic polymers (CPs) such as Lipofectamine and TurboFect are widely used for research in gene delivery, but their toxicity and low in vivo efficiency limited their further application. In the present study, we synthesized water-soluble APTES-IONPs and developed a combo gene delivery system based on APTES-IONPs and CPs. This system significantly increased gene-binding capacity, protected genes from degradation, and improved gene transfection efficiency for DNA and siRNA in both adherent and suspension cells. Because of its great biocompatibility, high gene-carrying ability, and very low cytotoxicity, this combo gene delivery system will be expected for a wide application, and it might provide a new method for gene therapy.

AcademyHealth's Delivery System Science Fellowship: Training Embedded Researchers to Design, Implement, and Evaluate New Models of Care.

PubMed

Kanani, Nisha; Hahn, Erin; Gould, Michael; Brunisholz, Kimberly; Savitz, Lucy; Holve, Erin

2017-07-01

AcademyHealth's Delivery System Science Fellowship (DSSF) provides a paid postdoctoral pragmatic learning experience to build capacity within learning healthcare systems to conduct research in applied settings. The fellowship provides hands-on training and professional leadership opportunities for researchers. Since its inception in 2012, the program has grown rapidly, with 16 health systems participating in the DSSF to date. In addition to specific projects conducted within health systems (and numerous publications associated with those initiatives), the DSSF has made several broader contributions to the field, including defining delivery system science, identifying a set of training objectives for researchers working in delivery systems, and developing a national collaborative network of care delivery organizations, operational leaders, and trainees. The DSSF is one promising approach to support higher-value care by promoting continuous learning and improvement in health systems. © 2017 Society of Hospital Medicine.

Drug self-delivery systems for cancer therapy.

PubMed

Qin, Si-Yong; Zhang, Ai-Qing; Cheng, Si-Xue; Rong, Lei; Zhang, Xian-Zheng

2017-01-01

Carrier-assistant drug delivery systems (DDSs) have been rapidly established for cancer therapy and great strides have been made in recent years. However, further development of DDSs is retarded by the aspects such as the low drug carrying capacity, carrier-induced toxicity and immunogenicity, complex synthesis manipulation. Drug self-delivery systems (DSDSs), in which active drugs exhibit nanoscale characteristic to realize intracellular delivery by themselves without the help of nanocarriers, have been rapidly developed to address these issues. In this review, we present a comprehensive summary of the recent advances in DSDSs for cancer therapy. After a brief introduction to the major types of DSDSs and their fabrication strategies, we emphatically discuss some representative achievements of these DSDSs for passive or/and positive targeting therapy, combinational therapy as well as theranostics. The design principle is explained and justified, which can cast a new light on developing drug delivery systems for cancer treatments. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dual AAV Vectors for Stargardt Disease.

PubMed

Trapani, Ivana

2018-01-01

Stargardt disease (STGD1), due to mutations in the large ABCA4 gene, is the most common inherited macular degeneration in humans. Attempts at developing gene therapy approaches for treatment of STGD1 are currently ongoing. Among all the vectors available for gene therapy of inherited retinal diseases, those based on adeno-associated viruses (AAV) are the most promising given the efficacy shown in various animal models and their excellent safety profile in humans, as confirmed in many ongoing clinical trials. However, one of the main obstacles for the use of AAV is their limited effective packaging capacity of about 5 kb. Taking advantage of the AAV genome's ability to concatemerize , others and we have recently developed dual AAV vectors to overcome this limit. We tested dual AAV vectors for ABCA4 delivery, and found that they transduce efficiently both mouse and pig photoreceptors , and rescue the Abca4-/- mouse retinal phenotype, indicating their potential for gene therapy of STGD1. This chapter details how we designed dual AAV vectors for the delivery of the ABCA4 gene and describes the techniques that can be explored to evaluate dual AAV transduction efficiency in vitro and in the retina, and their efficacy in the mouse model of STGD1.

Biomass-based magnetic fluorescent nanoparticles: One-step scalable synthesis, application as drug carriers and mechanism study.

PubMed

Li, Lei; Wang, Feijun; Shao, Ziqiang

2018-03-15

A biomass-based magnetic fluorescent nanoparticle (MFNPs) was successively in situ synthesized via a one-step high-gravity approach, which constructed by a magnetic core of Fe 3 O 4 nanoparticles, the fluorescent marker of carbon dots (CDs), and shells of chitosan (CS). The obtained MFNPs had a 10 nm average diameter and narrow particle size distribution, low cytotoxicity, superior fluorescent emission and superparamagnetic properties. The encapsulating and release 5-fluorouracil experiments confirmed that the introduction of CS/CDs effectively improved the drug loading capacity. Mechanism and kinetic studies proved that: (i) the monolayer adsorption was the main sorption mode under the studied conditions; (ii) the whole adsorption process was controlled by intra-liquid diffusion mass transfer and governed by chemisorption; and (iii) the release process was controlled by Fickian diffusion. These results demonstrated this method to one-step continuously produce MFNPs and the construction of non-toxic nanostructure possessed great superiority in currently Nano-delivery systems, which would show high application value in targeted drug delivery, magnetic fluid hyperthermia treatment, magnetic resonance imaging (MRI), in vitro testing and relative research. Copyright © 2017 Elsevier Ltd. All rights reserved.

Multifunctional polymeric micelles for delivery of drugs and siRNA

PubMed Central

Jhaveri, Aditi M.; Torchilin, Vladimir P.

2014-01-01

Polymeric micelles, self-assembling nano-constructs of amphiphilic copolymers with a core-shell structure have been used as versatile carriers for delivery of drugs as well as nucleic acids. They have gained immense popularity owing to a host of favorable properties including their capacity to effectively solubilize a variety of poorly soluble pharmaceutical agents, biocompatibility, longevity, high stability in vitro and in vivo and the ability to accumulate in pathological areas with compromised vasculature. Moreover, additional functions can be imparted to these micelles by engineering their surface with various ligands and cell-penetrating moieties to allow for specific targeting and intracellular accumulation, respectively, to load them with contrast agents to confer imaging capabilities, and incorporating stimuli-sensitive groups that allow drug release in response to small changes in the environment. Recently, there has been an increasing trend toward designing polymeric micelles which integrate a number of the above functions into a single carrier to give rise to “smart,” multifunctional polymeric micelles. Such multifunctional micelles can be envisaged as key to improving the efficacy of current treatments which have seen a steady increase not only in hydrophobic small molecules, but also in biologics including therapeutic genes, antibodies and small interfering RNA (siRNA). The purpose of this review is to highlight recent advances in the development of multifunctional polymeric micelles specifically for delivery of drugs and siRNA. In spite of the tremendous potential of siRNA, its translation into clinics has been a significant challenge because of physiological barriers to its effective delivery and the lack of safe, effective and clinically suitable vehicles. To that end, we also discuss the potential and suitability of multifunctional polymeric micelles, including lipid-based micelles, as promising vehicles for both siRNA and drugs. PMID:24795633

Nanocarrier-mediated drugs targeting cancer stem cells: an emerging delivery approach.

PubMed

Malhi, Sarandeep; Gu, Xiaochen

2015-07-01

Cancer stem cells (CSCs) play an important role in the development of drug resistance, metastasis and recurrence. Current conventional therapies do not commonly target CSCs. Nanocarrier-based delivery systems targeting cancer cells have entered a new era of treatment, where specific targeting to CSCs may offer superior outcomes to efficient cancer therapies. This review discusses the involvement of CSCs in tumor progression and relevant mechanisms associated with CSCs resistance to conventional chemo- and radio-therapies. It highlights CSCs-targeted strategies that are either under evaluation or could be explored in the near future, with a focus on various nanocarrier-based delivery systems of drugs and nucleic acids to CSCs. Novel nanocarriers targeting CSCs are presented in a cancer-specific way to provide a current perspective on anti-CSCs therapeutics. The field of CSCs-targeted therapeutics is still emerging with a few small molecules and macromolecules currently proving efficacy in clinical trials. However considering the complexities of CSCs and existing delivery difficulties in conventional anticancer therapies, CSC-specific delivery systems would face tremendous technical and clinical challenges. Nanocarrier-based approaches have demonstrated significant potential in specific drug delivery and targeting; their success in CSCs-targeted drug delivery would not only significantly enhance anticancer treatment but also address current difficulties associated with cancer resistance, metastasis and recurrence.

Aviation industry overview, fiscal year 1998

DOT National Transportation Integrated Search

1999-02-01

The contents of this research report are listed as follows: Industry overview; U.S. economic outlook; Passenger enplanements and aircraft departures; Traffic and seat capacity; Financial results; Air carrier aircraft orders and deliveries; General av...

Periodic Heterogeneous Vehicle Routing Problem With Driver Scheduling

NASA Astrophysics Data System (ADS)

Mardiana Panggabean, Ellis; Mawengkang, Herman; Azis, Zainal; Filia Sari, Rina

2018-01-01

The paper develops a model for the optimal management of logistic delivery of a given commodity. The company has different type of vehicles with different capacity to deliver the commodity for customers. The problem is then called Periodic Heterogeneous Vehicle Routing Problem (PHVRP). The goal is to schedule the deliveries according to feasible combinations of delivery days and to determine the scheduling of fleet and driver and routing policies of the vehicles. The objective is to minimize the sum of the costs of all routes over the planning horizon. We propose a combined approach of heuristic algorithm and exact method to solve the problem.

Nanoparticle Drug- and Gene-eluting Stents for the Prevention and Treatment of Coronary Restenosis

PubMed Central

Yin, Rui-Xing; Yang, De-Zhai; Wu, Jin-Zhen

2014-01-01

Percutaneous coronary intervention (PCI) has become the most common revascularization procedure for coronary artery disease. The use of stents has reduced the rate of restenosis by preventing elastic recoil and negative remodeling. However, in-stent restenosis remains one of the major drawbacks of this procedure. Drug-eluting stents (DESs) have proven to be effective in reducing the risk of late restenosis, but the use of currently marketed DESs presents safety concerns, including the non-specificity of therapeutics, incomplete endothelialization leading to late thrombosis, the need for long-term anti-platelet agents, and local hypersensitivity to polymer delivery matrices. In addition, the current DESs lack the capacity for adjustment of the drug dose and release kinetics appropriate to the disease status of the treated vessel. The development of efficacious therapeutic strategies to prevent and inhibit restenosis after PCI is critical for the treatment of coronary artery disease. The administration of drugs using biodegradable polymer nanoparticles as carriers has generated immense interest due to their excellent biocompatibility and ability to facilitate prolonged drug release. Despite the potential benefits of nanoparticles as smart drug delivery and diagnostic systems, much research is still required to evaluate potential toxicity issues related to the chemical properties of nanoparticle materials, as well as to their size and shape. This review describes the molecular mechanism of coronary restenosis, the use of DESs, and progress in nanoparticle drug- or gene-eluting stents for the prevention and treatment of coronary restenosis. PMID:24465275

Hydro-economic analysis of groundwater pumping for irrigated agriculture in California's Central Valley, USA

NASA Astrophysics Data System (ADS)

Medellín-Azuara, Josué; MacEwan, Duncan; Howitt, Richard E.; Koruakos, George; Dogrul, Emin C.; Brush, Charles F.; Kadir, Tariq N.; Harter, Thomas; Melton, Forrest; Lund, Jay R.

2015-09-01

As in many places, groundwater in California (USA) is the major alternative water source for agriculture during drought, so groundwater's availability will drive some inevitable changes in the state's water management. Currently, agricultural, environmental, and urban uses compete for groundwater, resulting in substantial overdraft in dry years with lowering of water tables, which in turn increases pumping costs and reduces groundwater pumping capacity. In this study, SWAP (an economic model of agricultural production and water use in California) and C2VISim (the California Department of Water Resources groundwater model for California's Central Valley) are connected. This paper examines the economic costs of pumping replacement groundwater during drought and the potential loss of pumping capacity as groundwater levels drop. A scenario of three additional drought years continuing from 2014 show lower water tables in California's Central Valley and loss of pumping capacity. Places without access to groundwater and with uncertain surface-water deliveries during drought are the most economically vulnerable in terms of crop revenues, employment and household income. This is particularly true for Tulare Lake Basin, which relies heavily on water imported from the Sacramento-San Joaquin Delta. Remote-sensing estimates of idle agricultural land between 2012 and 2014 confirm this finding. Results also point to the potential of a portfolio approach for agriculture, in which crop mixing and conservation practices have substantial roles.

Nanobiotechnology-based drug delivery in brain targeting.

PubMed

Dinda, Subas C; Pattnaik, Gurudutta

2013-01-01

Blood brain barrier (BBB) found to act as rate limiting factor in drug delivery to brain in combating the central nervous system (CNS) disorders. Such limiting physiological factors include the reticuloendothelial system and protein opsonization, which present across BBB, play major role in reducing the passage of drug. Several approaches employed to improve the drug delivery across the BBB. Nanoparticles (NP) are the solid colloidal particle ranges from 1 to 1000 nm in size utilized as career for drug delivery. At present NPs are found to play a significant advantage over the other methods of available drug delivery systems to deliver the drug across the BBB. Nanoparticles may be because of its size and functionalization characteristics able to penetrate and facilitate the drug delivery through the barrier. There are number of mechanisms and strategies found to be involved in this process, which are based on the type of nanomaterials used and its combination with therapeutic agents, such materials include liposomes, polymeric nanoparticles and non-viral vectors of nano-sizes for CNS gene therapy, etc. Nanotechnology is expected to reduce the need for invasive procedures for delivery of therapeutics to the CNS. Some devices such as implanted catheters and reservoirs however will still be needed to overcome the problems in effective drug delivery to the CNS. Nanomaterials are found to improve the safety and efficacy level of drug delivery devices in brain targeting. Nanoegineered devices are found to be delivering the drugs at cellular levels through nono-fluidic channels. Different drug delivery systems such as liposomes, microspheres, nanoparticles, nonogels and nonobiocapsules have been used to improve the bioavailability of the drug in the brain, but microchips and biodegradable polymeric nanoparticulate careers are found to be more effective therapeutically in treating brain tumor. The physiological approaches also utilized to improve the transcytosis capacity of specific receptors expressed across the BBB. It is found that the low density lipoproteins related protein (LPR) with engineered peptide compound (EpiC) formed the platform incorporating the Angiopep peptide as a new effective therapeutics. The current challenges are to design and develop the drug delivery careers, which must be able to deliver the drug across the BBB at a safe and effective manner. Nanoparticles are found to be effective careers in delivery of conventional drugs, recombinant proteins, vaccines as well as nucleotides. Nanoparticlulate drug delivery systems are found to be improving in the pharmacokinetic strategies of the drug molecules such as biodistribution, bioavailability and drug release characteristics in a controlled and effective manner with site specific drug delivery targeting to tissue or cell with reduction in toxic manifestation. Therefore, the use of nanotechnology in the field of pharmaceutical biotechnology helps in improving the drug delivery strategy including the kinetics and therapeutic index to solve the delivery problems of some biotech drugs including the recombinant proteins and oligonucleotides. This review is made to provide an insight to the role of nanobiotechnology in drug delivery and drug targeting to brain and its recent advances in the field of drug delivery systems.

Carbohydrate coated, folate functionalized colloidal graphene as a nanocarrier for both hydrophobic and hydrophilic drugs.

PubMed

Maity, Amit Ranjan; Chakraborty, Atanu; Mondal, Avijit; Jana, Nikhil R

2014-03-07

Although graphene based drug delivery has gained significant recent interest, the synthesis of colloidal graphene based nanocarriers with high drug loading capacities and with targeting ligands at the outer surface is a challenging issue. We have synthesized carbohydrate coated and folate functionalized colloidal graphene which can be used as a nanocarrier for a wide variety of hydrophobic and hydrophilic drugs. The synthesized colloidal graphene is loaded with paclitaxol, camptothecin, doxorubicin, curcumin and used for their targeted delivery to cancer cells. We demonstrate that this drug loaded functional graphene nanocarrier can successfully deliver drugs into target cells and offers an enhanced therapeutic performance. The reported approach can be extended to the cellular delivery of other hydrophobic and hydrophilic drugs and the simultaneous delivery of multiple drugs.

Discovery and Delivery of Synergistic Chemotherapy Drug Combinations to Tumors

NASA Astrophysics Data System (ADS)

Camacho, Kathryn Militar

Chemotherapy combinations for cancer treatments harbor immense therapeutic potentials which have largely been untapped. Of all diseases, clinical studies of drug combinations are the most prevalent in oncology, yet their effectiveness is disputable, as complete tumor regressions are rare. Our research has been devoted towards developing delivery vehicles for combinations of chemotherapy drugs which elicit significant tumor reduction yet limit toxicity in healthy tissue. Current administration methods assume that chemotherapy combinations at maximum tolerable doses will provide the greatest therapeutic effect -- a presumption which often leads to unprecedented side effects. Contrary to traditional administration, we have found that drug ratios rather than total cumulative doses govern combination therapeutic efficacy. In this thesis, we have developed nanoparticles to incorporate synergistic ratios of chemotherapy combinations which significantly inhibit cancer cell growth at lower doses than would be required for their single drug counterparts. The advantages of multi-drug incorporation in nano-vehicles are many: improved accumulation in tumor tissue via the enhanced permeation and retention effect, limited uptake in healthy tissue, and controlled exposure of tumor tissue to optimal synergistic drug ratios. To exploit these advantages for polychemotherapy delivery, two prominent nanoparticles were investigated: liposomes and polymer-drug conjugates. Liposomes represent the oldest class of nanoparticles, with high drug loading capacities and excellent biocompatibility. Polymer-drug conjugates offer controlled drug incorporations through reaction stoichiometry, and potentially allow for delivery of precise ratios. Here, we show that both vehicles, when armed with synergistic ratios of chemotherapy drugs, significantly inhibit tumor growth in an aggressive mouse breast carcinoma model. Furthermore, versatile drug incorporation methods investigated here can be broadly applied to various agents. Findings from our research can potentially widen the therapeutic window of chemotherapy combinations by emphasizing investigations of optimal drug ratios rather than maximum drug doses and by identifying appropriate nanoparticles for their delivery. Application of these concepts can ultimately help capture the full therapeutic potential of combination regimens.

Integrating community health workers within Patient Protection and Affordable Care Act implementation.

PubMed

Islam, Nadia; Nadkarni, Smiti Kapadia; Zahn, Deborah; Skillman, Megan; Kwon, Simona C; Trinh-Shevrin, Chau

2015-01-01

The Patient Protection and Affordable Care Act's (PPACA) emphasis on community-based initiatives affords a unique opportunity to disseminate and scale up evidence-based community health worker (CHW) models that integrate CHWs within health care delivery teams and programs. Community health workers have unique access and local knowledge that can inform program development and evaluation, improve service delivery and care coordination, and expand health care access. As a member of the PPACA-defined health care workforce, CHWs have the potential to positively impact numerous programs and reduce costs. This article discusses different strategies for integrating CHW models within PPACA implementation through facilitated enrollment strategies, patient-centered medical homes, coordination and expansion of health information technology (HIT) efforts, and also discusses payment options for such integration. Title V of the PPACA outlines a plan to improve access to and delivery of health care services for all individuals, particularly low-income, underserved, uninsured, minority, health disparity, and rural populations. Community health workers' role as trusted community leaders can facilitate accurate data collection, program enrollment, and provision of culturally and linguistically appropriate, patient- and family-centered care. Because CHWs already support disease management and care coordination services, they will be critical to delivering and expanding patient-centered medical homes and Health Home services, especially for communities that suffer disproportionately from multiple chronic diseases. Community health workers' unique expertise in conducting outreach make them well positioned to help enroll people in Medicaid or insurance offered by Health Benefit Exchanges. New payment models provide opportunities to fund and sustain CHWs. Community health workers can support the effective implementation of PPACA if the capacity and potential of CHWs to serve as cultural brokers and bridges among medically underserved communities and health care delivery systems is fully tapped. Patient Protection and Affordable Care Act and current payment structures provide an unprecedented and important vehicle for integrating and sustaining CHWs as part of these new delivery and enrollment models.

Integrating Community Health Workers Within Patient Protection and Affordable Care Act Implementation

PubMed Central

Islam, Nadia; Nadkarni, Smiti Kapadia; Zahn, Deborah; Skillman, Megan; Kwon, Simona C.; Trinh-Shevrin, Chau

2015-01-01

Context The Patient Protection and Affordable Care Act’s (PPACA) emphasis on community-based initiatives affords a unique opportunity to disseminate and scale up evidence-based community health worker (CHW) models that integrate CHWs within health care delivery teams and programs. Community health workers have unique access and local knowledge that can inform program development and evaluation, improve service delivery and care coordination, and expand health care access. As a member of the PPACA-defined health care workforce, CHWs have the potential to positively impact numerous programs and reduce costs. Objective This article discusses different strategies for integrating CHW models within PPACA implementation through facilitated enrollment strategies, patient-centered medical homes, coordination and expansion of health information technology (HIT) efforts, and also discusses payment options for such integration. Results Title V of the PPACA outlines a plan to improve access to and delivery of health care services for all individuals, particularly low-income, underserved, uninsured, minority, health disparity, and rural populations. Community health workers’ role as trusted community leaders can facilitate accurate data collection, program enrollment, and provision of culturally and linguistically appropriate, patient- and family-centered care. Because CHWs already support disease management and care coordination services, they will be critical to delivering and expanding patient-centered medical homes and Health Home services, especially for communities that suffer disproportionately from multiple chronic diseases. Community health workers’ unique expertise in conducting outreach make them well positioned to help enroll people in Medicaid or insurance offered by Health Benefit Exchanges. New payment models provide opportunities to fund and sustain CHWs. Conclusion Community health workers can support the effective implementation of PPACA if the capacity and potential of CHWs to serve as cultural brokers and bridges among medically underserved communities and health care delivery systems is fully tapped. Patient Protection and Affordable Care Act and current payment structures provide an unprecedented and important vehicle for integrating and sustaining CHWs as part of these new delivery and enrollment models. PMID:25414955

Fusogenic-Oligoarginine Peptide-Mediated Delivery of siRNAs Targeting the CIP2A Oncogene into Oral Cancer Cells

PubMed Central

Cantini, Liliana; Attaway, Christopher C.; Butler, Betsy; Andino, Lourdes M.; Sokolosky, Melissa L.; Jakymiw, Andrew

2013-01-01

Despite a better understanding of the pathogenesis of oral cancer, its treatment outcome remains poor. Thus, there is a need for new therapeutic strategies to improve the prognosis of this disease. RNA interference (RNAi) appears to be a promising therapeutic tool for the treatment of many diseases, including oral cancer. However, an obstacle for RNAi-mediated therapies has been delivery, in particular, the retention of small interfering RNAs (siRNAs) in endosomes and their subsequent degradation in lysosomes, resulting in inefficient gene silencing. Thus, the current study examined the feasibility of designing and utilizing a peptide, termed 599, consisting of a synthetic influenza virus-derived endosome-disruptive fusogenic peptide sequence and a stretch of cationic cell-penetrating nona(D-arginine) residues, to deliver siRNAs into oral cancer cells and induce silencing of the therapeutic target, CIP2A, an oncoprotein overexpressed in various human malignancies including oral cancer. Increasing the 599 peptide-to-siRNA molar ratio demonstrated a higher binding capacity for siRNA molecules and enhanced siRNA delivery into the cytoplasm of oral cancer cells. In fact, quantitative measurements of siRNA delivery into cells demonstrated that a 50∶1 peptide-to-siRNA molar ratio could deliver 18-fold higher amounts of siRNAs compared to cells treated with siRNA alone with no significant long-term cytotoxic effects. Most importantly, the 599 peptide-mediated siRNA delivery promoted significant CIP2A mRNA and protein silencing which resulted in decreased oral cancer cell invasiveness and anchorage-independent growth. Together, these data demonstrate that a chimeric peptide consisting of a fusogenic sequence, in combination with cell-penetrating residues, can be used to effectively deliver siRNAs into oral cancer cells and induce the silencing of its target gene, potentially offering a new therapeutic strategy in combating oral cancer. PMID:24019920

Regulation of decellularized tissue remodeling via scaffold-mediated lentiviral delivery in anatomically-shaped osteochondral constructs.

PubMed

Rowland, Christopher R; Glass, Katherine A; Ettyreddy, Adarsh R; Gloss, Catherine C; Matthews, Jared R L; Huynh, Nguyen P T; Guilak, Farshid

2018-05-30

Cartilage-derived matrix (CDM) has emerged as a promising scaffold material for tissue engineering of cartilage and bone due to its native chondroinductive capacity and its ability to support endochondral ossification. Because it consists of native tissue, CDM can undergo cellular remodeling, which can promote integration with host tissue and enables it to be degraded and replaced by neotissue over time. However, enzymatic degradation of decellularized tissues can occur unpredictably and may not allow sufficient time for mechanically competent tissue to form, especially in the harsh inflammatory environment of a diseased joint. The goal of the current study was to engineer cartilage and bone constructs with the ability to inhibit aberrant inflammatory processes caused by the cytokine interleukin-1 (IL-1), through scaffold-mediated delivery of lentiviral particles containing a doxycycline-inducible IL-1 receptor antagonist (IL-1Ra) transgene on anatomically-shaped CDM constructs. Additionally, scaffold-mediated lentiviral gene delivery was used to facilitate spatial organization of simultaneous chondrogenic and osteogenic differentiation via site-specific transduction of a single mesenchymal stem cell (MSC) population to overexpress either chondrogenic, transforming growth factor-beta 3 (TGF-β3), or osteogenic, bone morphogenetic protein-2 (BMP-2), transgenes. Controlled induction of IL-1Ra expression protected CDM hemispheres from inflammation-mediated degradation, and supported robust bone and cartilage tissue formation even in the presence of IL-1. In the absence of inflammatory stimuli, controlled cellular remodeling was exploited as a mechanism for fusing concentric CDM hemispheres overexpressing BMP-2 and TGF-β3 into a single bi-layered osteochondral construct. Our findings demonstrate that site-specific delivery of inducible and tunable transgenes confers spatial and temporal control over both CDM scaffold remodeling and neotissue composition. Furthermore, these constructs provide a microphysiological in vitro joint organoid model with site-specific, tunable, and inducible protein delivery systems for examining the spatiotemporal response to pro-anabolic and/or inflammatory signaling across the osteochondral interface. Copyright © 2018 Elsevier Ltd. All rights reserved.

Nano-scale gene delivery systems; current technology, obstacles, and future directions.

PubMed

Garcia-Guerra, Antonio; Dunwell, Thomas L; Trigueros, Sonia

2018-01-07

Within the different applications of nanomedicine currently being developed, nano-gene delivery is appearing as an exciting new technique with the possibility to overcome recognised hurdles and fulfill several biological and medical needs. The central component of all delivery systems is the requirement for the delivery of genetic material into cells, and for them to eventually reside in the nucleus where their desired function will be exposed. However, genetic material does not passively enter cells; thus, a delivery system is necessary. The emerging field of nano-gene delivery exploits the use of new materials and the properties that arise at the nanometre-scale to produce delivery vectors that can effectively deliver genetic material into a variety of different types of cells. The novel physicochemical properties of the new delivery vectors can be used to address the current challenges existing in nucleic acid delivery in vitro and in vivo. While there is a growing interest in nanostructure-based gene delivery, the field is still in its infancy, and there is yet much to discover about nanostructures and their physicochemical properties in a biological context. We carry out an organized and focused search of bibliographic databases. Our results suggest that despite new breakthroughs in nanostructure synthesis and advanced characterization techniques, we still face many barriers in producing highly efficient and non-toxic delivery systems. In this review, we overview the types of systems currently used for clinical and biomedical research applications along with their advantages and disadvantages, as well as discussing barriers that arise from nano-scale interactions with biological material. In conclusion, we hope that by bringing the far reaching multidisciplinary nature of nano-gene delivery to light, new targeted nanotechnology-bases strategies are developed to overcome the major challenges covered in this review. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Promoting cancer screening within the patient centered medical home.

PubMed

Sarfaty, Mona; Wender, Richard; Smith, Robert

2011-01-01

While consensus has grown that primary care is the essential access point in a high-performing health care system, the current model of primary care underperforms in both chronic disease management and prevention. The Patient Centered Medical Home model (PCMH) is at the center of efforts to reinvent primary care practice, and is regarded as the most promising approach to addressing the burden of chronic disease, improving health outcomes, and reducing health spending. However, the potential for the medical home to improve the delivery of cancer screening (and preventive services in general) has received limited attention in both conceptualization and practice. Medical home demonstrations to date have included few evidence-based preventive services in their outcome measures, and few have evaluated the effect of different payment models. Decreasing use of hospitals and emergency rooms and an emphasis on improving chronic care represent improvements in effective delivery of healthcare, but leave opportunities for reducing the burden of cancer untouched. Data confirm that what does or does not happen in the primary care setting has a substantial impact on cancer outcomes. Insofar as cancer is the leading cause of death before age 80, the PCMH model must prioritize adherence to cancer screening according to recommended guidelines, and systems, financial incentives, and reimbursements must be aligned to achieve that goal. This article explores capacities that are needed in the medical home model to facilitate the integration of cancer screening and other preventive services. These capacities include improved patient access and communication, health risk assessments, periodic preventive health exams, use of registries that store cancer risk information and screening history, ability to track and follow up on tests and referrals, feedback on performance, and payment models that reward cancer screening. Copyright © 2011 American Cancer Society, Inc.

Antigen discovery and delivery of subunit vaccines by nonliving bacterial ghost vectors.

PubMed

Walcher, Petra; Mayr, Ulrike B; Azimpour-Tabrizi, Chakameh; Eko, Francis O; Jechlinger, Wolfgang; Mayrhofer, Peter; Alefantis, Tim; Mujer, Cesar V; DelVecchio, Vito G; Lubitz, Werner

2004-12-01

The bacterial ghost (BG) platform system is a novel vaccine delivery system endowed with intrinsic adjuvant properties. BGs are nonliving Gram-negative bacterial cell envelopes which are devoid of their cytoplasmic contents, yet maintain their cellular morphology and antigenic structures, including bioadhesive properties. The main advantages of BGs as carriers of subunit vaccines include their ability to stimulate a high immune response and to target the carrier itself to primary antigen-presenting cells. The intrinsic adjuvant properties of BGs enhance the immune response to target antigens, including T-cell activation and mucosal immunity. Since native and foreign antigens can be carried in the envelope complex of BGs, combination vaccines with multiple antigens of diverse origin can be presented to the immune system simultaneously. Beside the capacity of BGs to function as carriers of protein antigens, they also have a high loading capacity for DNA. Thus, loading BGs with recombinant DNA takes advantage of the excellent bioavailability for DNA-based vaccines and the high expression rates of the DNA-encoded antigens in target cell types such as macrophages and dendritic cells. There are many spaces within BGs including the inner and outer membranes, the periplasmic space and the internal lumen which can carry antigens, DNA or mediators of the immune response. All can be used for subunit antigen to design new vaccine candidates with particle presentation technology. In addition, the fact that BGs can also carry piggyback large-size foreign antigen particles, increases the technologic usefulness of BGs as combination vaccines against viral and bacterial pathogens. Furthermore, the BG antigen carriers can be stored as freeze-dried preparations at room temperature for extended periods without loss of efficacy. The potency, safety and relatively low production cost of BGs offer a significant technical advantage over currently utilized vaccine technologies.

HBOC Vasoactivity: Interplay Between Nitric Oxide Scavenging and Capacity to Generate Bioactive Nitric Oxide Species

PubMed Central

Friedman, Joel M.

2013-01-01

Abstract Significance: Despite many advances in blood substitute research, the development of materials that are effective in maintaining blood volume and oxygen delivery remains a priority for emergency care and trauma. Clinical trials on hemoglobin (Hb)-based oxygen carriers (HBOCs) have not provided information on the mechanism of toxicity, although all commercial formulations have safety concerns. Specifically, it is important to reconcile the different hypotheses of Hb toxicity, such as nitric oxide (NO) depletion and oxidative reactions, to provide a coherent molecular basis for designing a safe HBOC. Recent Advances: HBOCs with different sizes often exhibit differences in the degree of HBOC-induced vasoactivity. This has been attributed to differences in the degree of NO scavenging and in the extent of Hb extravasation. Additionally, it is appears that Hb can undergo reactions that compensate for NO scavenging by generating bioactive forms of NO. Critical Issues: Engineering modifications to enhance bioactive NO production can result in diminished oxygen delivery by virtue of increased oxygen affinity. This strategy can prevent the HBOC from fulfilling the intended goal on preserving oxygenation; however, the NO production effects will increase perfusion and oxygen transport. Future Directions: Hb modifications influence NO scavenging and the capacity of certain HBOCs to compensate for NO scavenging through nitrite-mediated reactions that generate bioactive NO. Based on the current understanding of these NO-related factors, possible synthetic strategies are presented that address how HBOC formulations can be prepared that: (i) effectively deliver oxygen, (ii) maintain tissue perfusion, and (iii) limit/reverse underlying inflammation within the vasculature. Antioxid. Redox Signal. 18, 2284–2297. PMID:23249305

The enhanced longevity and liver targetability of Paclitaxel by hybrid liposomes encapsulating Paclitaxel-conjugated gold nanoparticles.

PubMed

Bao, Quan-Ying; Zhang, Ning; Geng, Dong-Dong; Xue, Jing-Wei; Merritt, Mackenzie; Zhang, Can; Ding, Ya

2014-12-30

Organic and inorganic drug delivery systems both demonstrate their own advantages and challenges in practical applications. Combining these two drug delivery strategies in one system is expected to solve their current issues and achieve desirable functions. In this paper, gold nanoparticles (GNPs) and liposomes have been chosen as the model systems to construct a hybrid system and investigate its performance for the tumor therapy of Paclitaxel (PTX). The thiol-terminated polyethylene glycol (PEG400)-PTX derivative has been covalently modified on the surface of GNPs, followed by the encapsulation of PTX-conjugated GNPs (PTX-PEG400@GNPs) in liposomes. The hybrid liposomes solve the solubility and stability problems of gold conjugates and show high drug loading capacity. In vitro PTX release from the hybrid system maintains the similar sustained behavior demonstrated in its conjugates. Under the protection of a biocompatible liposome shell, encapsulated PTX shows enhanced circulation longevity and liver targetability compared to Taxol(®) and PTX-PEG400@GNPs suspension in the pharmacokinetic and biodistribution studies. These indicate that encapsulating drug-conjugated inorganic nanoparticles inside organic carriers maintains the superiority of both vehicles and improves the performance of hybrid systems. Although these attributes of hybrid liposomes lead to a better therapeutic capacity in a murine liver cancer model than that of the comparison groups, it shows no significant difference from Taxol(®) and conjugate suspension. This result could be due to the delayed and sustained drug release from the system. However, it indicates the promising potential for these hybrid liposomes will allow further construction of a compound preparation with improved performance that is based on their enhanced longevity and liver targetability of Paclitaxel. Copyright © 2014 Elsevier B.V. All rights reserved.

Pilot Field Test of Electrokinetically-Delivered and Thermally Activated Persulfate (EKTAP) for Remediation of Chlorinated Solvents in Clay

NASA Astrophysics Data System (ADS)

O'Carrol, D. M.; Head, N.; Chowdhury, A. I.; Inglis, A.; Garcia, A. N.; Reynolds, D. A.; Hayman, J.; Hogberg, D.; Austrins, L. M.; Sidebottom, A.; Auger, M.; Eimers, J.; Gerhard, J.

2017-12-01

Remediation of low-permeability soils that are contaminated with chlorinated solvents is challenging. In-situ chemical oxidation (ISCO) with persulfate is promising, however, the delivery of the oxidant by hydraulic gradient is limited in low-permeability soils. Electrokinetic (EK) enhanced transport of amendments has shown the potential to overcome these limitations. In particular, the combined technology of EK-delivered and thermally activated persulfate (EKTAP) has been recently demonstrated in the laboratory as promising in these challenging environments (Chowdhury A. I. (2016) Hydraulic and Electrokinetic Delivery of Remediants for In-situ Remediation. Electronic Thesis and Dissertation Repository, Paper 4135). This study presents the first pilot field test to evaluate EKTAP to enhance the distribution and effectiveness of persulfate in clayey soil. The pilot field test was conducted at a contaminated site formerly occupied by a chlorinated solvent production facility. In the EK transport phase, 925 L of 40 g/L persulfate was injected over 57 days, during which 9A of direct current (DC) was applied between two electrodes spaced 3 m apart. In the subsequent heating phase, 10A of alternate current (AC) was applied across the same electrodes for an additional 70 days. Extensive sampling of soil and groundwater in this EKTAP cell were compared to those from two parallel control cells, one with EK only and one with no electrodes. Results indicated that EK can significantly increase transport rates of persulfate in clayey soil. Persulfate activation primarily occurred in the period of DC application, indicating that the natural reduction capacity of the clay soil had a significant impact on persulfate decomposition. Temperature mapping indicated that AC current was able to increase soil temperatures, validating the EKTAP concept. Degradation of chlorinated compounds, in particular, 1-2, dichloroethane (1,2- DCA), was observed to be substantial in areas of persulfate delivery. Studies are ongoing to evaluate the mineral oxidation of the persulfate and how to optimize the system for both EK and ERH applications. This study nevertheless demonstrates for the first time at the field scale that EKTAP can result in enhanced amendment transport and remediation of low permeability strata.

Dental mesenchymal stem cells encapsulated in alginate hydrogel co-delivery microencapsulation system for cartilage regeneration

PubMed Central

Moshaverinia, Alireza; Xu, Xingtian; Chen, Chider; Akiyama, Kentaro; Snead, Malcolm L; Shi, Songtao

2013-01-01

Dental-derived MSCs are promising candidates for cartilage regeneration, with high chondrogenic differentiation capacity. This property contributes to making dental MSCs an advantageous therapeutic option compared to current treatment modalities. The MSC delivery vehicle is the principal determinant for the success of MSC-mediated cartilage regeneration therapies. The objectives of this study were to: (1) develop a novel co-delivery system based on TGF-β1 loaded RGD-coupled alginate microspheres encapsulating Periodontal Ligament Stem Cells (PDLSCs) or Gingival Mesenchymal Stem Cells (GMSCs); and (2) investigate dental MSC viability and chondrogenic differentiation in alginate microspheres. The results revealed the sustained release of TGF-β1 from the alginate microspheres. After 4 weeks of chondrogenic differentiation in vitro, PDLSCs, GMSCs as well as human bone marrow mesenchymal stem cells (hBMMSC) (as positive control) revealed chondrogenic gene expression markers (Col II and Sox-9) via qPCR, as well as matrix positively stained by toluidine blue and safranin-O. In animal studies, ectopic cartilage tissue regeneration was observed inside and around the transplanted microspheres, confirmed by histochemical and immunofluorescent staining. Interestingly, PDLSCs showed more chondrogenesis than GMSCs and hBMMSCs (P<0.05). Taken together, these results suggest that RGD-modified alginate microencapsulating dental MSCs make a promising candidate for cartilage regeneration. Our results highlight the vital role played by the microenvironment, as well as value of presenting inductive signals for viability and differentiation of MSCs. PMID:23891740

Epilepsy services in Ireland: 'A survey of people with epilepsy in relation to satisfaction, preferences and information provision'.

PubMed

Bennett, Louise; Bergin, Michael; Gooney, Martina; Doherty, Colin P; Synnott, Cara; Wells, John S G

2015-07-01

A challenge facing modern health care systems is to develop and implement new models of service that deliver increased capacity while providing a higher-quality, more cost-effective service within resource constraints. Incorporating the experience of people with epilepsy must be seen as central to the effectiveness of service design and delivery. This paper, therefore, reports the views of people with epilepsy with regards to health service delivery in Ireland. A cross-sectional descriptive survey design involving both quantitative and qualitative items was administered to a convenience sample of one hundred and two people with epilepsy (n=102) attending an epilepsy specialist centre. Despite high levels of satisfaction with hospital and primary care, participants offered several suggestions to improve healthcare delivery, such as: less delay in accessing specialist care and hospital appointments; better communication; and easier access to investigatory services. Findings demonstrate that for people with epilepsy the burden of the disorder is substantial and complex encompassing social, psychological and structural difficulties. Poor information provision particularly among women is reported. Furthermore, a lack of empowerment in people with epilepsy is highlighted. This study has implications for the reform and development of epilepsy services in relation to practice, education and research. It provides a basis for an evaluation of current practice and identifies opportunities for future service reorganization to improve the quality and efficiency of healthcare provision. Copyright © 2015 Elsevier B.V. All rights reserved.

Assessing the feasibility of using uniaxial accelerometers with an online support platform in the delivery of a community-based exercise referral scheme.

PubMed

Hawkins, Jemma L; Oliver, Emily J; Wyatt-Williams, Jeannie; Scale, Elaine; van Woerden, Hugo C

2014-10-01

Exercise referral schemes are established within community-based health care; however, they have been criticized for failing to evidence long-term behavior change relative to usual care. As such, recent reviews have called for refinement of their delivery with a focus on embedded strategies targeting client motivation. This research letter presents findings from an initial pilot trial conducted within Wales' National Exercise Referral Scheme (NERS), examining the feasibility of using validated physical activity monitoring devices and an accompanying online platform within standard scheme delivery. 30 individuals referred to generic or cardiovascular pathways were offered the system; of these 17 agreed to participate. Common reasons for declining were clustered into lack of technology literacy or access, condition severity, or fear of costs associated with losing the device. Analysis of follow-up interviews after 4 weeks of use indicated that while participants found the monitoring devices practical and informative, only a minority (n = 4) were using the system in full. Crucially, the system element most aligned with contemporary theories of motivation (the online portal) was not used as expected. In addition, feedback from exercise referral professionals indicated that there were demands for support from clients, which might be mitigated by more effective independent system use. Recommendations for larger scale trials using similar systems include consideration of targeted patient groups, equity of access, and providing adequate technological support that is currently beyond the capacity of the NERS system. © The Author(s) 2014.

Acute and impaired wound healing: pathophysiology and current methods for drug delivery, part 2: role of growth factors in normal and pathological wound healing: therapeutic potential and methods of delivery.

PubMed

Demidova-Rice, Tatiana N; Hamblin, Michael R; Herman, Ira M

2012-08-01

This is the second of 2 articles that discuss the biology and pathophysiology of wound healing, reviewing the role that growth factors play in this process and describing the current methods for growth factor delivery into the wound bed.

Acute and Impaired Wound Healing: Pathophysiology and Current Methods for Drug Delivery, Part 2: Role of Growth Factors in Normal and Pathological Wound Healing: Therapeutic Potential and Methods of Delivery

PubMed Central

Demidova-Rice, Tatiana N.; Hamblin, Michael R.; Herman, Ira M.

2012-01-01

This is the second of 2 articles that discuss the biology and pathophysiology of wound healing, reviewing the role that growth factors play in this process and describing the current methods for growth factor delivery into the wound bed. PMID:22820962

76 FR 68831 - Funds Availability (NOFA) Inviting Applications for the Community Development Financial...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-07

... provide additional narrative explaining their lack of access to loans, equity investments, or Financial... Narrative 10 Target Market Needs 10 Responsiveness to Target Market Needs 40 Delivery Capacity 40 TOTAL...

Strengthening the primary care workforce to deliver community case management for child health in rural Indonesia.

PubMed

Setiawan, Agus; Dawson, Angela

2017-10-02

Objectives The aim of the present study was to report on the implementation of community case management (CCM) to reduce infant mortality in a rural district, namely Kutai Timur, Kalimantan Indonesia. Methods An interpretive qualitative methodology was used. In-depth interviews were conducted with 18 primary healthcare workers (PHCWs), and PHCWs were observed during a consultation with mothers to gain insight into the delivery of the new protocol and workforce issues. The field notes and interview transcripts were analysed thematically. Results PHCWs reported that their performance had improved as a result of increased knowledge and confidence. The implementation of CCM had also reportedly enhanced the PHCWs' clinical reasoning. However, the participants noted confusion surrounding their role in prescribing medication. Conclusions CCM is viewed as a useful model of care in terms of enhancing the capacity of rural PHCWs to provide child health care and improve the uptake of life-saving interventions. However, work is needed to strengthen the workforce and to fully integrate CCM into maternal and child health service delivery across Indonesia. What is known about the topic? Indonesia has successfully reduced infant mortality in the past 10 years. However, concerns remain regarding issues related to disparities between districts. The number of infant deaths in rural areas tends to be staggeringly high compared with that in the cities. One of the causes is inadequate access to child health care. What does this paper add? CCM is a model of care that is designed to address childhood illnesses in limited-resource settings. In CCM, PHCWs are trained to deliver life-saving interventions to sick children in rural communities. In the present study, CCM improved the capacity of PHCWs to treat childhood illnesses. What are the implications for practitioners? CCM can be considered to strengthen PHCWs' competence in addressing infant mortality in areas where access to child health care is challenging. Policy regarding task shifting needs to be examined further so that CCM can be integrated into current health service delivery in Indonesia.

Polysaccharides as Bacterial Antiadhesive Agents and "Smart" Constituents for Improved Drug Delivery Systems Against Helicobacter pylori Infection.

PubMed

Menchicchi, Bianca; Hensel, Andreas; Goycoolea, Francisco M

2015-01-01

The standard eradication treatment of the hostile Helicobacter pylori (H. pylori) stomach infection is facing increasing alarming antibiotic resistance worldwide and calls for alternative strategies to the use of antibiotics. One new perspective in this direction is cytoprotective compounds for targeted prevention of the adhesion of the bacteria to the stomach host cell and to inhibit the bacterial cell-cell communication via quorum sensing by specific inhibitors. Bacterial adhesion of H. pylori to the host cells is mainly mediated by carbohydrate-protein interactions. Therefore, the use of polyvalent carbohydrates, (e.g. plant-derived polysaccharides), as potential antiadhesive compounds, seems to be a promising tool to prevent the initial docking of the bacterium to the stomach cells. Polysaccharides are common constituents of daily food, either as starch or as dietary fiber and often also function as excipients for galenic drug-delivery formulations. In addition, polysaccharides with defined pharmacodynamics action against bacterial outer membrane proteins can have potential as therapeutic tools in the treatment of bacterial infections. Some polysaccharides are known to possess antibacterial properties against gram-positive bacteria, others to inhibit bacterial colonization by blocking specific carbohydrate receptors involved in host-bacteria interaction. This mode of action is advocated as alternative antiadhesion therapy. Ongoing research is also seeking for polysaccharide-based nanoformulations with potential for local drug delivery at the stomach as novel H. pylori therapies. These approaches pose challenges concerned with the stability of the nanomaterials in the harsh conditions of the gastric environment and their capacity to adhere to the stomach mucosa. In a global scenario, geographical diversity and social habits, namely lifestyle and dietary factors, influence the prevalence of the H. pylori-associated diseases and their severity. In this context, the exploration of the biological activity of plant-derived products or polysaccharides commonly present in foods is increasingly becoming more and more attractive. This review aims to present the current state-of-the-art on the antiadhesive capacity of different polysaccharide families, on polysaccharide-based nanosystems and the proof-of-concept evidence of their potential use as alternative medicines against H. pylori.

Current and emerging lipid-based systems for transdermal drug delivery.

PubMed

Singla, Sumeet K; Sachdeva, Vishal

2015-01-01

Developing a transdermal drug delivery system is a challenging task considering the selective permeability of the skin and the physicochemical properties the drug must possess to permeate through the skin. Lipid-based drug delivery systems have contributed a great deal in this direction in the last few decades, and thereby have helped to expand the range of therapeutic molecules that can be delivered through the skin in a safe and effective manner. Additionally, vesicular delivery systems such as nanoparticles and emulsions have also played important roles in providing alternative novel approaches for drug delivery. In this article, we will discuss some of the current and future lipid-based systems for transdermal drug delivery along with the associated challenges.

Ocular drug delivery systems: An overview

PubMed Central

Patel, Ashaben; Cholkar, Kishore; Agrahari, Vibhuti; Mitra, Ashim K

2014-01-01

The major challenge faced by today’s pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration, especially for the treatment of anterior segment diseases. Delivery of drugs to the targeted ocular tissues is restricted by various precorneal, dynamic and static ocular barriers. Also, therapeutic drug levels are not maintained for longer duration in target tissues. In the past two decades, ocular drug delivery research acceleratedly advanced towards developing a novel, safe and patient compliant formulation and drug delivery devices/techniques, which may surpass these barriers and maintain drug levels in tissues. Anterior segment drug delivery advances are witnessed by modulation of conventional topical solutions with permeation and viscosity enhancers. Also, it includes development of conventional topical formulations such as suspensions, emulsions and ointments. Various nanoformulations have also been introduced for anterior segment ocular drug delivery. On the other hand, for posterior ocular delivery, research has been immensely focused towards development of drug releasing devices and nanoformulations for treating chronic vitreoretinal diseases. These novel devices and/or formulations may help to surpass ocular barriers and associated side effects with conventional topical drops. Also, these novel devices and/or formulations are easy to formulate, no/negligibly irritating, possess high precorneal residence time, sustain the drug release, and enhance ocular bioavailability of therapeutics. An update of current research advancement in ocular drug delivery necessitates and helps drug delivery scientists to modulate their think process and develop novel and safe drug delivery strategies. Current review intends to summarize the existing conventional formulations for ocular delivery and their advancements followed by current nanotechnology based formulation developments. Also, recent developments with other ocular drug delivery strategies employing in situ gels, implants, contact lens and microneedles have been discussed. PMID:25590022

Ocular drug delivery systems: An overview.

PubMed

Patel, Ashaben; Cholkar, Kishore; Agrahari, Vibhuti; Mitra, Ashim K

The major challenge faced by today's pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration, especially for the treatment of anterior segment diseases. Delivery of drugs to the targeted ocular tissues is restricted by various precorneal, dynamic and static ocular barriers. Also, therapeutic drug levels are not maintained for longer duration in target tissues. In the past two decades, ocular drug delivery research acceleratedly advanced towards developing a novel, safe and patient compliant formulation and drug delivery devices/techniques, which may surpass these barriers and maintain drug levels in tissues. Anterior segment drug delivery advances are witnessed by modulation of conventional topical solutions with permeation and viscosity enhancers. Also, it includes development of conventional topical formulations such as suspensions, emulsions and ointments. Various nanoformulations have also been introduced for anterior segment ocular drug delivery. On the other hand, for posterior ocular delivery, research has been immensely focused towards development of drug releasing devices and nanoformulations for treating chronic vitreoretinal diseases. These novel devices and/or formulations may help to surpass ocular barriers and associated side effects with conventional topical drops. Also, these novel devices and/or formulations are easy to formulate, no/negligibly irritating, possess high precorneal residence time, sustain the drug release, and enhance ocular bioavailability of therapeutics. An update of current research advancement in ocular drug delivery necessitates and helps drug delivery scientists to modulate their think process and develop novel and safe drug delivery strategies. Current review intends to summarize the existing conventional formulations for ocular delivery and their advancements followed by current nanotechnology based formulation developments. Also, recent developments with other ocular drug delivery strategies employing in situ gels, implants, contact lens and microneedles have been discussed.

Operationalising emergency care delivery in sub-Saharan Africa: consensus-based recommendations for healthcare facilities.

PubMed

Calvello, Emilie J B; Tenner, Andrea G; Broccoli, Morgan C; Skog, Alexander P; Muck, Andrew E; Tupesis, Janis P; Brysiewicz, Petra; Teklu, Sisay; Wallis, Lee; Reynolds, Teri

2016-08-01

A major barrier to successful integration of acute care into health systems is the lack of consensus on the essential components of emergency care within resource-limited environments. The 2013 African Federation of Emergency Medicine Consensus Conference was convened to address the growing need for practical solutions to further implementation of emergency care in sub-Saharan Africa. Over 40 participants from 15 countries participated in the working group that focused on emergency care delivery at health facilities. Using the well-established approach developed in the WHO's Monitoring Emergency Obstetric Care, the workgroup identified the essential services delivered-signal functions-associated with each emergency care sentinel condition. Levels of emergency care were assigned based on the expected capacity of the facility to perform signal functions, and the necessary human, equipment and infrastructure resources identified. These consensus-based recommendations provide the foundation for objective facility capacity assessment in developing emergency health systems that can bolster strategic planning as well as facilitate monitoring and evaluation of service delivery. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Role of faith-based and nongovernment organizations in the provision of obstetric services in 3 African countries.

PubMed

Vogel, Joshua Peter; Betrán, Ana Pilar; Widmer, Mariana; Souza, João Paulo; Gülmezoglu, Ahmet Metin; Seuc, Armando; Torloni, Maria Regina; Mengestu, Tigest Ketsela; Merialdi, Mario

2012-12-01

We sought to describe obstetric care capacity of nongovernment organization (NGO)-/faith-based organization (FBO)-run institutions compared to government-run institutions in 3 African countries using the World Health Organization Global Survey. We also compared delivery characteristics and outcomes. This is a descriptive analysis of the 22 NGO-/FBO-run institutions in Uganda, Kenya and Democratic Republic of Congo delivering 11,594 women, compared to 20 government-run institutions delivering 25,825 women in the same countries and period. Infrastructure, obstetric services, diagnostic facilities, and anesthesiology at NGO/FBO institutions were comparable to government institutions. Women delivering at NGO/FBO institutions had more antenatal care, antenatal complications, and cesarean delivery. NGO/FBO institutions had higher obstetrician attendance and lower rates of eclampsia, preterm birth, stillbirth, Apgar <7, and neonatal near miss. NGO/FBO institutions are comparable to government institutions in capacity to deliver obstetric care. NGO/FBOs have been found effective in providing delivery care in developing countries and should be appropriately recognized by stakeholders in their efforts to assist nations achieve international goals. Copyright © 2012 Mosby, Inc. All rights reserved.

Travel time to maternity care and its effect on utilization in rural Ghana: a multilevel analysis.

PubMed

Masters, Samuel H; Burstein, Roy; Amofah, George; Abaogye, Patrick; Kumar, Santosh; Hanlon, Michael

2013-09-01

Rates of neonatal and maternal mortality are high in Ghana. In-facility delivery and other maternal services could reduce this burden, yet utilization rates of key maternal services are relatively low, especially in rural areas. We tested a theoretical implication that travel time negatively affects the use of in-facility delivery and other maternal services. Empirically, we used geospatial techniques to estimate travel times between populations and health facilities. To account for uncertainty in Ghana Demographic and Health Survey cluster locations, we adopted a novel approach of treating the location selection as an imputation problem. We estimated a multilevel random-intercept logistic regression model. For rural households, we found that travel time had a significant effect on the likelihood of in-facility delivery and antenatal care visits, holding constant education, wealth, maternal age, facility capacity, female autonomy, and the season of birth. In contrast, a facility's capacity to provide sophisticated maternity care had no detectable effect on utilization. As the Ghanaian health network expands, our results suggest that increasing the availability of basic obstetric services and improving transport infrastructure may be important interventions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Influence of cationic lipid concentration on properties of lipid–polymer hybrid nanospheres for gene delivery

PubMed Central

Bose, Rajendran JC; Arai, Yoshie; Ahn, Jong Chan; Park, Hansoo; Lee, Soo-Hong

2015-01-01

Nanoparticles have been widely used for nonviral gene delivery. Recently, cationic hybrid nanoparticles consisting of two different materials were suggested as a promising delivery vehicle. In this study, nanospheres with a poly(d,l-lactic-co-glycolic acid) (PLGA) core and cationic lipid shell were prepared, and the effect of cationic lipid concentrations on the properties of lipid polymer hybrid nanocarriers investigated. Lipid–polymer hybrid nanospheres (LPHNSs) were fabricated by the emulsion-solvent evaporation method using different concentrations of cationic lipids and characterized for size, surface charge, stability, plasmid DNA-binding capacity, cytotoxicity, and transfection efficiency. All LPHNSs had narrow size distribution with positive surface charges (ζ-potential 52–60 mV), and showed excellent plasmid DNA-binding capacity. In vitro cytotoxicity measurements with HEK293T, HeLa, HaCaT, and HepG2 cells also showed that LPHNSs exhibited less cytotoxicity than conventional transfection agents, such as Lipofectamine and polyethyleneimine–PLGA. As cationic lipid concentrations increased, the particle size of LPHNSs decreased while their ζ-potential increased. In addition, the in vitro transfection efficiency of LPHNSs increased as lipid concentration increased. PMID:26379434

A prodrug micellar carrier assembled from polymers with pendant farnesyl thiosalicylic acid moieties for improved delivery of paclitaxel.

PubMed

Sun, Jingjing; Chen, Yichao; Li, Ke; Huang, Yixian; Fu, Xiaofeng; Zhang, Xiaolan; Zhao, Wenchen; Wei, Yuan; Xu, Liang; Zhang, Peijun; Venkataramanan, Raman; Li, Song

2016-10-01

In order to achieve enhanced and synergistic delivery of paclitaxel (PTX), a hydrophobic anticancer agent, two novel prodrug copolymers, POEG15-b-PFTS6 and POEG15-b-PFTS16 composed of hydrophilic poly(oligo(ethylene glycol) methacrylate) (POEG) and hydrophobic farnesylthiosalicylate (FTS, a nontoxic Ras antagonist) blocks, were synthesized. Both POEG-b-PFTS polymers were able to form micelles with intrinsic antitumor activity in vitro and in vivo. Employing these micelles as a carrier to load PTX, their drug loading capacity, stability, in vivo biodistribution and tumor inhibition effect were evaluated. PTX/POEG15-b-PFTS16 mixed micelles exhibited an excellent stability of 9days at 4°C with a PTX loading capacity of 8.2%, which was more effective than PTX/POEG15-b-PFTS6 mixed micelles. In vivo biodistribution data showed that DiR-loaded POEG-b-PFTS micelles were more effectively localized in the tumor than in other organs. Moreover, both PTX/POEG-b-PFTS micelles showed significantly higher antitumor activity than Taxol in a 4T1.2 murine breast tumor model, and the tumor inhibition and animal survival followed the order of PTX/POEG15-b-PFTS16>PTX/POEG15-b-PFTS6>POEG15-b-PFTS16>Taxol≈POEG15-b-PFTS6. Our data suggest that POEG-b-PFTS micelles are a promising anticancer drug carrier that warrants more studies in the future. Polymerization of drug-based monomer represents a facile and precise method to obtain well-defined polymeric prodrug amphiphiles. Currently, most reports largely focus on the synthesis methods and the biophysical properties. There is limited information about their anti-tumor activity and delivery function as prodrug carriers in vitro and in vivo. In this manuscript, we report the development of two novel prodrug copolymers, POEG15-b-PFTS6 and POEG15-b-PFTS16 composed of hydrophilic poly(oligo(ethylene glycol) methacrylate) (POEG) and hydrophobic farnesylthiosalicylate (FTS, a nontoxic Ras antagonist) blocks. Both POEG-b-PFTS polymers were able to self-assemble into nano-sized micelles with intrinsic antitumor activity in vitro and in vivo. More importantly, POEG-b-PFTS polymers were effective in forming stable mixed micelles with various anticancer agents including PTX, DOX, docetaxel, gefitinib, and imatinib. Delivery of PTX via our new carrier led to significantly improved antitumor activity, suggesting effective PTX/FTS combination therapy. We believe that our study shall be of broad interest to the readers in the fields of biomaterials and drug delivery. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Silk-Based Biomaterials for Sustained Drug Delivery

PubMed Central

Yucel, Tuna; Lovett, Michael L.; Kaplan, David L.

2014-01-01

Silk presents a rare combination of desirable properties for sustained drug delivery, including aqueous-based purification and processing options without chemical cross-linkers, compatibility with common sterilization methods, controllable and surface-mediated biodegradation into non-inflammatory by-products, biocompatibility, utility in drug stabilization, and robust mechanical properties. A versatile silk-based toolkit is currently available for sustained drug delivery formulations of small molecule through macromolecular drugs, with a promise to mitigate several drawbacks associated with other degradable sustained delivery technologies in the market. Silk-based formulations utilize silk’s well-defined nano- through microscale structural hierarchy, stimuli-responsive self-assembly pathways and crystal polymorphism, as well as sequence and genetic modification options towards targeted pharmaceutical outcomes. Furthermore, by manipulating the interactions between silk and drug molecules, near-zero order sustained release may be achieved through diffusion- and degradation-based release mechanisms. Because of these desirable properties, there has been increasing industrial interest in silk-based drug delivery systems currently at various stages of the developmental pipeline from pre-clinical to FDA-approved products. Here, we discuss the unique aspects of silk technology as a sustained drug delivery platform and highlight the current state of the art in silk-based drug delivery. We also offer a potential early development pathway for silk-based sustained delivery products. PMID:24910193

Efficient funding: a path to improving Aboriginal healthcare in Australia?

PubMed

Lloyd, Jane E; Wise, Marilyn J

2010-11-01

To identify the factors that contribute to the under-resourcing of Aboriginal health and to explore the impact that funding arrangements have on the implementation of Aboriginal health policy. Qualitative study based on 35 in-depth interviews with a purposive sample of frontline health professionals involved in health policy and service provision in the Northern Territory. Participants described three factors that contributed to the under-resourcing of Aboriginal health: inefficient funding arrangements, mainstream programs being inappropriate for Aboriginal Australians, and competing interests determining the allocation of resources. Insufficient capacity within the healthcare system undermines the multilevel implementation process whereby organisations need to have the capacity to recognise new policy ideas, assess their relevance to their existing work and strategic plan and to be able to incorporate the relevant new ideas into day-to-day practice. Insufficient resources for Aboriginal health were found to be a barrier to implementing Aboriginal health policy. Inadequate resources result from the cumbersome allocation of funding rather than simply the amount of funding provided to Aboriginal healthcare. Monitoring government performance and ensuring the efficient allocation of funds would allow us to develop the delivery system for Aboriginal healthcare and therefore provide greater opportunities to capitalise on current interventions and future efforts.

Hospitals as learning organizations: fostering innovation through interactive learning.

PubMed

Dias, Casimiro; Escoval, Ana

2015-01-01

The article aims to provide an analytical understanding of hospitals as "learning organizations." It further analyzes the development of learning organizations as a way to enhance innovation and performance in the hospital sector. The article pulls together primary data on organizational flexibility, innovation, and performance from 95 administrators from hospital boards in Portugal, collected through a survey, interviews with hospital's boards, and a nominal group technique with a panel of experts on health systems. Results show that a combination of several organizational traits of the learning organization enhances its capacity for innovation development. The logistic model presented reveals that hospitals classified as "advanced learning organizations" have 5 times more chance of developing innovation than "basic learning organizations." Empirical findings further pointed out incentives, standards, and measurement requirements as key elements for integration of service delivery systems and expansion of the current capacity for structured and real-time learning in the hospital sector. The major implication arising from this study is that policy needs to combine instruments that promote innovation opportunities and incentives, with instruments stimulating the further development of the core components of learning organizations. Such a combination of policy instruments has the potential to ensure a wide external cooperation through a learning infrastructure.

A roadmap for acute care training of frontline Healthcare workers in LMICs.

PubMed

Shah, Nirupa; Bhagwanjee, Satish; Diaz, Janet; Gopalan, P D; Appiah, John Adabie

2017-10-01

This 10-step roadmap outlines explicit procedures for developing, implementing and evaluating short focused training programs for acute care in low and middle income countries (LMICs). A roadmap is necessary to develop resilient training programs that achieve equivalent outcomes despite regional variability in human capacity and infrastructure. Programs based on the roadmap should address shortfalls in human capacity and access to care in the short term and establish the ground work for health systems strengthening in the long term. The primary targets for acute care training are frontline healthcare workers at the clinic level. The programs will differ from others currently available with respect to the timelines, triage method, therapeutic interventions and potential for secondary prevention. The roadmap encompasses multiple iterative cycles of the Plan-Do-Study-Act framework. Core features are integration of frontline trainees with the referral system while promoting research, quality improvement and evaluation from the bottom-up. Training programs must be evidence based, developed along action timelines and use adaptive training methods. A systems approach is essential because training programs that take cognizance of all factors that influence health care delivery have the potential to produce health systems strengthening (HSS). Copyright © 2017 Elsevier Inc. All rights reserved.

Doubling transmission capacity in optical wireless system by antenna horizontal- and vertical-polarization multiplexing.

PubMed

Li, Xinying; Yu, Jianjun; Zhang, Junwen; Dong, Ze; Chi, Nan

2013-06-15

We experimentally demonstrate 2×56 Gb/s two-channel polarization-division-multiplexing quadrature-phase-shift-keying signal delivery over 80 km single-mode fiber-28 and 2 m Q-band (33-50 GHz) wireless link, adopting antenna horizontal- (H-) and vertical-polarization (V-polarization) multiplexing. At the wireless receiver, classic constant-modulus-algorithm equalization based on digital signal processing can realize polarization demultiplexing and remove the crosstalk at the same antenna polarization. By adopting antenna polarization multiplexing, the signal baud rate and performance requirements for optical and wireless devices can be reduced but at the cost of double antennas and devices, while wireless transmission capacity can also be increased but at the cost of stricter requirements for V-polarization. The isolation is only about 19 dB when V-polarization deviation approaches 10°, which will affect high-speed (>50 Gb/s) wireless delivery.

A comparison inhibitory effects of cisplatin and MNPs-PEG-cisplatin on the adhesion capacity of bone metastatic breast cancer.

PubMed

Mokhtari, Mohammad Javad; Koohpeima, Fatemeh; Mohammadi, Hadi

2017-10-01

To date, high mortality in women due to malignancy breast cancer related to the metastasis to the bone is a significant challenge. As, magnetic nanoparticles (MNPs) conjugated with the biocompatible polymers was employed for the delivery of some hydrophobic anticancer agents, the main aim of the current research was to assess whether cisplatin-loaded MNPs enhanced the anticancer effect of free cisplatin in breast cancer cells. MNPs decorated with PEG were synthesized by an improved coprecipitation technique, and then cisplatin was loaded onto the MNPs via a simple mixing method. Afterward, its morphology, size, chemical structure, magnetic property, hydrodynamic diameter, zeta potential, and crystal structure were characterized by scanning and transmittance electron microscopy, Fourier transforms infrared spectroscopy, vibrating sample magnetometer, dynamic light scattering, and X-ray powder diffraction and flame atomic absorption spectroscopy respectively. Additionally, the effects of cisplatin and MNPs-PEG-cisplatin on viability, migration and adhesion capacity of T47D cells were investigated by evaluating α2-integrin and β1-integrin; mRNAs were assessed by real-time RT-PCR. Consequently, the in vitro assay results showed a considerable dose-dependent inhibitory effect of cisplatin and MNPs-PEG-cisplatin on proliferation, migration, and adhesion of T47D cells. Finally, current research was shown that MNPs-PEG-cisplatin strongly increased anticancer effects compared with free cisplatin in the T47D cell line. © 2017 John Wiley & Sons A/S.

Health Promotion Education in India: Present Landscape and Future Vistas

PubMed Central

Pati, Sanghamitra; Sharma, Kavya; Zodpey, Sanjay; Chauhan, Kavita; Dobe, Madhumita

2012-01-01

‘Health promotion is the process of enabling people to increase control over and to improve their health’. This stream of public health is emerging as a critical domain within the realm of disease prevention. Over the last two decades, the curative model of health care has begun a subtle shift towards a participatory model of health promotion emphasizing upon practice of healthy lifestyles and creating healthy communities. Health promotion encompasses five key strategies with health communication and education as its cornerstones. Present study is an attempt to explore the current situation of health promotion education in India with an aim to provide a background for capacity building in health promotion. A systematic predefined method was adopted to collect and compile information on existing academic programs pertaining to health promotion and health education/communication. Results of the study reveal that currently health promotion education in India is fragmented and not uniform across institutes. It is yet to be recognized as a critical domain of public health education. Mostly teaching of health promotion is limited to health education and communication. There is a need for designing programmes for short-term and long-term capacity building, with focus on innovative methods and approaches. Public health institutes and associations could play a proactive role in designing and imparting academic programs on health promotion. Enhancing alliances with various institutes involved in health promotion activities and networking among public health and medical institutes as well as health services delivery systems would be more productive. PMID:22980352

Supercapacitive transport of pharmacologic agents using nanoporous gold electrodes.

PubMed

Gittard, Shaun D; Pierson, Bonnie E; Ha, Cindy M; Wu, Chung-An Max; Narayan, Roger J; Robinson, David B

2010-02-01

In this study, nanoporous gold supercapacitors were produced by electrochemical dealloying of gold-silver alloy. Scanning electron microscopy and energy dispersive X-ray spectroscopy confirmed completion of the dealloying process and generation of a porous gold material with approximately 10 nm diameter pores. Cyclic voltammetry and chronoamperometry of the nanoporous gold electrodes indicated that these materials exhibited supercapacitor behavior. The storage capacity of the electrodes measured by chronoamperometry was approximately 3 mC at 200 mV. Electrochemical storage and voltage-controlled delivery of two model pharmacologic agents, benzylammonium and salicylic acid, was demonstrated. These results suggest that capacitance-based storage and delivery of pharmacologic agents may serve as an alternative to conventional drug delivery methods.

Overview on zein protein: a promising pharmaceutical excipient in drug delivery systems and tissue engineering.

PubMed

Labib, Gihan

2018-01-01

Natural pharmaceutical excipients have been applied extensively in the past decades owing to their safety and biocompatibility. Zein, a natural protein of plant origin offers great benefit over other synthetic polymers used in controlled drug and biomedical delivery systems. It was used in a variety of medical fields including pharmaceutical and biomedical drug targeting, vaccine, tissue engineering, and gene delivery. Being biodegradable and biocompatible, the current review focuses on the history and the medical application of zein as an attractive still promising biopolymer. Areas covered: The current review gives a broadscope on zein as a still promising protein excipient in different fields. Zein- based drug and biomedical delivery systems are discussed with special focus on current and potential application in controlled drug delivery systems, and tissue engineering. Expert opinion: Zein as a protein of natural origin can still be considered a promising polymer in the field of drug delivery systems as well as in tissue engineering. Although different researchers spotted light on zein application in different industrial fields extensively, the feasibility of its use in the field of drug delivery replenished by investigators in recent years has not yet been fully approached.

Effect of delivery condition on desorption rate of ZrCo metal hydride bed for fusion fuel cycle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kang, H.G.; Yun, S.H.; Chung, D.

2015-03-15

For the safety of fusion fuel cycle, hydrogen isotope gases including tritium are stored as metal hydride form. To satisfy fueling requirement of fusion machine, rapid delivery from metal hydride bed is one of major factors for the development of tritium storage and delivery system. Desorption from metal hydride depends on the operation scenario by pressure and temperature control of the bed. The effect of operation scenario and pump performance on desorption rate of metal hydride bed was experimentally investigated using ZrCo bed. The results showed that the condition of pre-heating scenario before actual delivery of gas affected the deliverymore » performance. Different pumps were connected to desorption line from bed and the effect of pump capacity on desorption rate were also found to be significant. (authors)« less

Attitudes, norms and controls influencing lifestyle risk factor management in general practice.

PubMed

Ampt, Amanda J; Amoroso, Cheryl; Harris, Mark F; McKenzie, Suzanne H; Rose, Vanessa K; Taggart, Jane R

2009-08-26

With increasing rates of chronic disease associated with lifestyle behavioural risk factors, there is urgent need for intervention strategies in primary health care. Currently there is a gap in the knowledge of factors that influence the delivery of preventive strategies by General Practitioners (GPs) around interventions for smoking, nutrition, alcohol consumption and physical activity (SNAP). This qualitative study explores the delivery of lifestyle behavioural risk factor screening and management by GPs within a 45-49 year old health check consultation. The aims of this research are to identify the influences affecting GPs' choosing to screen and choosing to manage SNAP lifestyle risk factors, as well as identify influences on screening and management when multiple SNAP factors exist. A total of 29 audio-taped interviews were conducted with 15 GPs and one practice nurse over two stages. Transcripts from the interviews were thematically analysed, and a model of influencing factors on preventive care behaviour was developed using the Theory of Planned Behaviour as a structural framework. GPs felt that assessing smoking status was straightforward, however some found assessing alcohol intake only possible during a formal health check. Diet and physical activity were often inferred from appearance, only being assessed if the patient was overweight. The frequency and thoroughness of assessment were influenced by the GPs' personal interests and perceived congruence with their role, the level of risk to the patient, the capacity of the practice and availability of time. All GPs considered advising and educating patients part of their professional responsibility. However their attempts to motivate patients were influenced by perceptions of their own effectiveness, with smoking causing the most frustration. Active follow-up and referral of patients appeared to depend on the GPs' orientation to preventive care, the patient's motivation, and cost and accessibility of services to patients. General practitioner attitudes, normative influences from both patients and the profession, and perceived external control factors (time, cost, availability and practice capacity) all influence management of behavioural risk factors. Provider education, community awareness raising, support and capacity building may improve the uptake of lifestyle modification interventions.

Regenerative Medicine for the Heart: Perspectives on Stem-Cell Therapy

PubMed Central

Cho, Gun-Sik; Fernandez, Laviel

2014-01-01

Abstract Significance: Despite decades of progress in cardiovascular biology and medicine, heart disease remains the leading cause of death, and there is no cure for the failing heart. Since heart failure is mostly caused by loss or dysfunction of cardiomyocytes (CMs), replacing dead or damaged CMs with new CMs might be an ideal way to reverse the disease. However, the adult heart is composed mainly of terminally differentiated CMs that have no significant self-regeneration capacity. Recent Advances: Stem cells have tremendous regenerative potential and, thus, current cardiac regenerative research has focused on developing stem cell sources to repair damaged myocardium. Critical Issues: In this review, we examine the potential sources of cells that could be used for heart therapies, including embryonic stem cells and induced pluripotent stem cells, as well as alternative methods for activating the endogenous regenerative mechanisms of the heart via transdifferentiation and cell reprogramming. We also discuss the current state of knowledge of cell purification, delivery, and retention. Future Directions: Efforts are underway to improve the current stem cell strategies and methodologies, which will accelerate the development of innovative stem-cell therapies for heart regeneration. Antioxid. Redox Signal. 21, 2018–2031. PMID:25133793

Control of neglected tropical diseases needs a long-term commitment.

PubMed

Zhang, Yaobi; MacArthur, Chad; Mubila, Likezo; Baker, Shawn

2010-10-29

Neglected tropical diseases are widespread, particularly in sub-Saharan Africa, affecting over 2 billion individuals. Control of these diseases has gathered pace in recent years, with increased levels of funding from a number of governmental or non-governmental donors. Focus has currently been on five major 'tool-ready' neglected tropical diseases (lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiasis and trachoma), using a package of integrated drug delivery according to the World Health Organization guidelines for preventive chemotherapy. Success in controlling these neglected tropical diseases has been achieved in a number of countries in recent history. Experience from these successes suggests that long-term sustainable control of these diseases requires: (1) a long-term commitment from a wider range of donors and from governments of endemic countries; (2) close partnerships of donors, World Health Organization, pharmaceutical industries, governments of endemic countries, communities, and non-governmental developmental organisations; (3) concerted action from more donor countries to provide the necessary funds, and from the endemic countries to work together to prevent cross-border disease transmission; (4) comprehensive control measures for certain diseases; and (5) strengthened primary healthcare systems as platforms for the national control programmes and capacity building through implementation of the programmes. The current level of funding for the control of neglected tropical diseases has never been seen before, but it is still not enough to scale up to the 2 billion people in all endemic countries. While more donors are sought, the stakeholders must work in a coordinated and harmonised way to identify the priority areas and the best delivery approaches to use the current funds to the maximum effect. Case management and other necessary control measures should be supported through the current major funding streams in order to achieve the objectives of the control of these diseases. For a long-term and sustainable effort, control of neglected tropical diseases should also be integrated into national primary healthcare systems.

Physically facilitating drug-delivery systems

PubMed Central

Rodriguez-Devora, Jorge I; Ambure, Sunny; Shi, Zhi-Dong; Yuan, Yuyu; Sun, Wei; Xu, Tao

2012-01-01

Facilitated/modulated drug-delivery systems have emerged as a possible solution for delivery of drugs of interest to pre-allocated sites at predetermined doses for predefined periods of time. Over the past decade, the use of different physical methods and mechanisms to mediate drug release and delivery has grown significantly. This emerging area of research has important implications for development of new therapeutic drugs for efficient treatments. This review aims to introduce and describe different modalities of physically facilitating drug-delivery systems that are currently in use for cancer and other diseases therapy. In particular, delivery methods based on ultrasound, electrical, magnetic and photo modulations are highlighted. Current uses and areas of improvement for these different physically facilitating drug-delivery systems are discussed. Furthermore, the main advantages and drawbacks of these technologies reviewed are compared. The review ends with a speculative viewpoint of how research is expected to evolve in the upcoming years. PMID:22485192

Evaluation of Roadmap to Achieve Energy Delivery Systems Cybersecurity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chavez, Adrian R.

The Department of Energy/Office of Electricity Delivery and Energy Reliability (DOE/OE) Cybersecurity for Energy Delivery Systems (CEDS) program is currently evaluating the Roadmap to Achieve Energy Delivery Systems Cybersecurity document that sets a vision and outlines a set of milestones. The milestones are divided into five strategic focus areas that include: 1. Build a Culture of Security; 2. Assess and Monitor Risk; 3. Develop and Implement New Protective Measures to Reduce Risk; 4. Manage Incidents; and 5. Sustain Security Improvements. The most current version of the roadmap was last updated in September of 2016. Sandia National Laboratories (SNL) has beenmore » tasked with revisiting the roadmap to update the current state of energy delivery systems cybersecurity protections. SNL is currently working with previous and current partners to provide feedback on which of the roadmap milestones have been met and to identify any preexisting or new gaps that are not addressed by the roadmap. The specific focus areas SNL was asked to evaluate are: 1. Develop and Implement New Protective Measures to Reduce Risk and 2. Sustain Security Improvements. SNL has formed an Industry Advisory Board (IAB) to assist in answering these questions. The IAB consists of previous partners on past CEDS funded efforts as well as new collaborators that have unique insights into the current state of cybersecurity within energy delivery systems. The IAB includes asset owners, utilities and vendors of control systems. SNL will continue to maintain regular communications with the IAB to provide various perspectives on potential future updates to further improve the breadth of cybersecurity coverage of the roadmap.« less

Continuing Professional Education Delivery Systems.

ERIC Educational Resources Information Center

Weeks, James P.

This investigation of delivery systems for continuing professional education provides an overview of current operational delivery systems in continuing professional education, drawing on experience as found in the literature. Learning theories and conclusions are woven into the descriptive text. Delivery systems profiled in the paper include the…

To The Biorefinery: Delivered Forestland and Agricultural Resources

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

2016-06-01

It can be challenging and costly to transport biomass feedstock supplies from the roadside, or farmgate, to a biorefinery. Given the geographic dispersion and lowbulk density of cellulosic feedstocks, cost effective scaling of commercial biorefinery operations requires overcoming many challenges. The Biomass Research and Development Board’s Feedstock Logistics Interagency Working Group identified four primary barriers related to biorefinery commercialization: • Capacity and efficiency of harvest and collection equipment • High-moisture content leading to degradation of biomass • Variable biomass quality upon arrival at the biorefinery • Costly transportation options.1 Further, feedstock supply systems do not currently mitigate risks such asmore » low crop yield, fire, or competition for resource use. Delivery and preprocessing improvements will allow for the development of a commercial-scale bioenergy industry that achieves national production and cost targets.« less

High-Capacity Communications from Martian Distances Part 4: Assessment of Spacecraft Pointing Accuracy Capabilities Required For Large Ka-Band Reflector Antennas

NASA Technical Reports Server (NTRS)

Hodges, Richard E.; Sands, O. Scott; Huang, John; Bassily, Samir

2006-01-01

Improved surface accuracy for deployable reflectors has brought with it the possibility of Ka-band reflector antennas with extents on the order of 1000 wavelengths. Such antennas are being considered for high-rate data delivery from planetary distances. To maintain losses at reasonable levels requires a sufficiently capable Attitude Determination and Control System (ADCS) onboard the spacecraft. This paper provides an assessment of currently available ADCS strategies and performance levels. In addition to other issues, specific factors considered include: (1) use of "beaconless" or open loop tracking versus use of a beacon on the Earth side of the link, and (2) selection of fine pointing strategy (body-fixed/spacecraft pointing, reflector pointing or various forms of electronic beam steering). Capabilities of recent spacecraft are discussed.

The skills gap in nursing management in South Africa: a sectoral analysis: a research paper.

PubMed

Pillay, Rubin

2010-03-01

To identify competencies important for effective nursing management and to assess managers' proficiency therein. A lack of management capacity has been identified as the key stumbling block to health delivery in South Africa. Despite nursing managers being central to overcoming the challenges facing health care, there has been a paucity of research that empirically evaluates their skill levels. A survey was conducted among 171 senior nursing managers in South Africa using a self-administered questionnaire. Public sector managers assessed themselves as being relatively less competent than private sector managers. The largest skill gaps for public sector managers were for 'ethico-legal', 'task-related' and 'controlling' skills whereas those for private sector managers were for 'ethico-legal', 'health-related ' and 'task-related' skills. This research confirmed the lack of management capacity within the health sector and identified areas in which the skills deficit was most significant for both the public and private sectors. These findings reflect the needs of nursing managers and will be useful in the conceptualization, design and delivery of health management programmes aimed at enhancing management and leadership capacity in the health sector in South Africa.

Some like it hot: Thermal tolerance and oxygen supply capacity in two eurythermal crustaceans.

PubMed

Ern, Rasmus; Huong, Do Thi Thanh; Phuong, Nguyen Thanh; Madsen, Peter Teglberg; Wang, Tobias; Bayley, Mark

2015-06-01

Thermal sensitivity of the cardiorespiratory oxygen supply capacity has been proposed as the cardinal link underlying the upper boundary of the temperature niche in aquatic ectotherms. Here we examined the evidence for this link in two eurythermal decapods, the Giant tiger shrimp (Penaeus monodon) and the European crayfish (Astacus astacus). We found that both species have a temperature resistant cardiorespiratory system, capable of maintaining oxygen delivery up to their upper critical temperature (Tcrit). In neither species was Tcrit reduced in hypoxia (60% air saturation) and both species showed an exponential increase in heart and gill ventilation rates up to their Tcrit. Further, failure of action potential conduction in preparations of A. astacus motor neurons coincided with Tcrit, indicating that compromised nervous function may provide the underlying determinant for Tcrit rather than oxygen delivery. At high temperatures, absolute aerobic scope was maintained in P. monodon, but reduced in A. astacus. However, A. astacus also displayed reduced exercise intensity indicating that impaired muscle performance with resulting reduced tissue oxygen demand may explain the reduced scope rather than insufficient oxygen supply capacity. This interpretation agrees with early literature on aquatic ectotherms, correlating loss of nervous function with impaired locomotion as temperatures approach Tcrit.

Effect of thiol pendant conjugates on plasmid DNA binding, release, and stability of polymeric delivery vectors.

PubMed

Bacalocostantis, Irene; Mane, Viraj P; Kang, Michael S; Goodley, Addison S; Muro, Silvia; Kofinas, Peter

2012-05-14

Polymers have attracted much attention as potential gene delivery vectors due to their chemical and structural versatility. However, several challenges associated with polymeric carriers, including low transfection efficiencies, insufficient cargo release, and high cytotoxicity levels have prevented clinical implementation. Strong electrostatic interactions between polymeric carriers and DNA cargo can prohibit complete cargo release within the cell. As a result, cargo DNA never reaches the cell's nucleus where gene expression takes place. In addition, highly charged cationic polymers have been correlated with high cytotoxicity levels, making them unsuitable carriers in vivo. Using poly(allylamine) (PAA) as a model, we investigated how pH-sensitive disulfide cross-linked polymer networks can improve the delivery potential of cationic polymer carriers. To accomplish this, we conjugated thiol-terminated pendant chains onto the primary amines of PAA using 2-iminothiolane, developing three new polymer vectors with 5, 13, or 20% thiol modification. Unmodified PAA and thiol-conjugated polymers were tested for their ability to bind and release plasmid DNA, their capacity to protect genetic cargo from enzymatic degradation, and their potential for endolysosomal escape. Our results demonstrate that polymer-plasmid complexes (polyplexes) formed by the 13% thiolated polymer demonstrate the greatest delivery potential. At high N/P ratios, all thiolated polymers (but not unmodified counterparts) were able to resist decomplexation in the presence of heparin, a negatively charged polysaccharide used to mimic in vivo polyplex-protein interactions. Further, all thiolated polymers exhibited higher buffering capacities than unmodified PAA and, therefore, have a greater potential for endolysosomal escape. However, 5 and 20% thiolated polymers exhibited poor DNA binding-release kinetics, making them unsuitable carriers for gene delivery. The 13% thiolated polymers, on the other hand, displayed high DNA binding efficiency and pH-sensitive release.

RESILIENCE OF THE HUMAN FETAL LUNG FOLLOWING STILLBIRTH

PubMed Central

De Paepe, Monique E.; Chu, Sharon; Heger, Nicholas; Hall, Susan; Mao, Quanfu

2013-01-01

Recent advances in pulmonary regenerative medicine have increased the demand for alveolar epithelial progenitor cells. Fetal lung tissues from spontaneous pregnancy losses may represent a neglected, yet ethically and societally acceptable source of alveolar epithelial cells. The aim of this study was to determine the regenerative capacity of fetal lungs obtained from second trimester stillbirths. Lung tissues were harvested from 11 stillborn fetuses (13–22 weeks’ gestation) at post-delivery intervals ranging from 10 to 41 hours and grafted to the renal subcapsular space of immune suppressed rats to provide optimal growth conditions. Histology, epithelial and alveolar type II cell proliferation, and surfactant protein-C mRNA expression were studied in preimplantation lung tissues and in xenografts at post-transplantation week 2. All xenografts displayed advanced architectural maturation compared with their respective preimplantation tissues, regardless of gestational age and post-delivery interval. The proliferative activity of the grafts was significantly higher than that of the preimplantation tissues (mean Ki-67 labeling index 26.7 ± 7.7% versus 14.7 ± 10.5%, P < 0.01). The proliferative activity of grafts obtained after a long (> 36 h) post-delivery interval was significantly higher than that of the corresponding preimplantation tissue, and equivalent to that of grafts obtained after a short post-delivery interval (< 14 h). The regenerative capacity of fetal lung tissue was greater at younger (13–17 weeks) than at older (19–22 weeks) gestational ages. The presence of inflammation/chorioamnionitis did not appear to affect graft regeneration. All grafts studied displayed robust surfactant protein-C mRNA expression. In conclusion, fetal lung tissues from second trimester stillbirths can regain their inherent high regenerative potential following short-term culture, even if harvested more than 36 hours after delivery. PMID:22168578

3 CFR 13527 - Executive Order 13527 of December 30, 2009. Establishing Federal Capability for the Timely...

Code of Federal Regulations, 2010 CFR

2010-01-01

... capacity for rapid residential delivery of medical countermeasures for self administration across all... of Defense, within 90 days of the date of this order, shall develop a concept of operations and...

Design-Build Highway Projects : A Review of Practices and Experiences, Final Report.

DOT National Transportation Integrated Search

2016-11-01

Texas has employed different project delivery methods in recent years in an effort to add capacity, reduce congestion, and improve the effectiveness and efficiency of the states transportation system. These transportation improvement projects are ...

76 FR 70535 - Notice of Funds Availability (NOFA) Inviting Applications for the Community Development Financial...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-14

... Populations is not required to provide additional narrative explaining their lack of access to loans, equity... Narrative 10 Target Market Needs 10 Responsiveness to Target Market Needs 40 Delivery Capacity 40 Total...

Synergistic effect of amino acids modified on dendrimer surface in gene delivery.

PubMed

Wang, Fei; Wang, Yitong; Wang, Hui; Shao, Naimin; Chen, Yuanyuan; Cheng, Yiyun

2014-11-01

Design of an efficient gene vector based on dendrimer remains a great challenge due to the presence of multiple barriers in gene delivery. Single-functionalization on dendrimer cannot overcome all the barriers. In this study, we synthesized a list of single-, dual- and triple-functionalized dendrimers with arginine, phenylalanine and histidine for gene delivery using a one-pot approach. The three amino acids play different roles in gene delivery: arginine is essential in formation of stable complexes, phenylalanine improves cellular uptake efficacy, and histidine increases pH-buffering capacity and minimizes cytotoxicity of the cationic dendrimer. A combination of these amino acids on dendrimer generates a synergistic effect in gene delivery. The dual- and triple-functionalized dendrimers show minimal cytotoxicity on the transfected NIH 3T3 cells. Using this combination strategy, we can obtain triple-functionalized dendrimers with comparable transfection efficacy to several commercial transfection reagents. Such a combination strategy should be applicable to the design of efficient and biocompatible gene vectors for gene delivery. Copyright © 2014 Elsevier Ltd. All rights reserved.

Interpenetrating Polymer Networks as Innovative Drug Delivery Systems

PubMed Central

Lohani, Alka; Singh, Garima; Bhattacharya, Shiv Sankar; Verma, Anurag

2014-01-01

Polymers have always been valuable excipients in conventional dosage forms, also have shown excellent performance into the parenteral arena, and are now capable of offering advanced and sophisticated functions such as controlled drug release and drug targeting. Advances in polymer science have led to the development of several novel drug delivery systems. Interpenetrating polymer networks (IPNs) have shown superior performances over the conventional individual polymers and, consequently, the ranges of applications have grown rapidly for such class of materials. The advanced properties of IPNs like swelling capacity, stability, biocompatibility, nontoxicity and biodegradability have attracted considerable attention in pharmaceutical field especially in delivering bioactive molecules to the target site. In the past few years various research reports on the IPN based delivery systems showed that these carriers have emerged as a novel carrier in controlled drug delivery. The present review encompasses IPNs, their types, method of synthesis, factors which affects the morphology of IPNs, extensively studied IPN based drug delivery systems, and some natural polymers widely used for IPNs. PMID:24949205

Construction of Hyaluronic Tetrasaccharide Clusters Modified Polyamidoamine siRNA Delivery System.

PubMed

Ma, Yingcong; Sha, Meng; Cheng, Shixuan; Yao, Wang; Li, Zhongjun; Qi, Xian-Rong

2018-06-14

The CD44 protein, as a predominant receptor for hyaluronan (HA), is highly expressed on the surface of multiple tumor cells. HA, as a targeting molecule for a CD44-contained delivery system, increases intracellular drug concentration in tumor tissue. However, due to the weak binding ability of hyaluronan oligosaccharide to CD44, targeting for tumor drug delivery has been restricted. In this study, we first use a HA tetrasaccharide cluster as the target ligand to enhance the binding ability to CD44. A polyamidoamine (PAMAM) dendrimer was modified by a HA tetrasaccharide cluster as a nonviral vector for small interfering RNA (siRNA) delivery. The dendrimer/siRNA nanocomplexes increased the cellular uptake capacity of siRNA through the CD44 receptor-mediated endocytosis pathway, allowing the siRNA to successfully escape the endosome/lysosome. Compared with the control group, nanocomplexes effectively reduced the expression of GFP protein and mRNA in MDA-MB-231-GFP cells. This delivery system provides a foundation to increase the clinical applications of PAMAM nanomaterials.

Biocompatibility of Chitosan Carriers with Application in Drug Delivery

PubMed Central

Rodrigues, Susana; Dionísio, Marita; Remuñán López, Carmen; Grenha, Ana

2012-01-01

Chitosan is one of the most used polysaccharides in the design of drug delivery strategies for administration of either biomacromolecules or low molecular weight drugs. For these purposes, it is frequently used as matrix forming material in both nano and micron-sized particles. In addition to its interesting physicochemical and biopharmaceutical properties, which include high mucoadhesion and a great capacity to produce drug delivery systems, ensuring the biocompatibility of the drug delivery vehicles is a highly relevant issue. Nevertheless, this subject is not addressed as frequently as desired and even though the application of chitosan carriers has been widely explored, the demonstration of systems biocompatibility is still in its infancy. In this review, addressing the biocompatibility of chitosan carriers with application in drug delivery is discussed and the methods used in vitro and in vivo, exploring the effect of different variables, are described. We further provide a discussion on the pros and cons of used methodologies, as well as on the difficulties arising from the absence of standardization of procedures. PMID:24955636

Building community resilience through mental health infrastructure and training in post-Katrina New Orleans.

PubMed

Springgate, Benjamin F; Wennerstrom, Ashley; Meyers, Diana; Allen, Charles E; Vannoy, Steven D; Bentham, Wayne; Wells, Kenneth B

2011-01-01

To describe a disaster recovery model focused on developing mental health services and capacity-building within a disparities-focused, community-academic participatory partnership framework. Community-based participatory, partnered training and services delivery intervention in a post-disaster setting. Post-Katrina Greater New Orleans community. More than 400 community providers from more than 70 health and social services agencies participated in the trainings. Partnered development of a training and services delivery program involving physicians, therapists, community health workers, and other clinical and non-clinical personnel to improve access and quality of care for mental health services in a post-disaster setting. Services delivery (outreach, education, screening, referral, direct treatment); training delivery; satisfaction and feedback related to training; partnered development of training products. Clinical services in the form of outreach, education, screening, referral and treatment were provided in excess of 110,000 service units. More than 400 trainees participated in training, and provided feedback that led to evolution of training curricula and training products, to meet evolving community needs over time. Participant satisfaction with training generally scored very highly. This paper describes a participatory, health-focused model of community recovery that began with addressing emerging, unmet mental health needs using a disparities-conscious partnership framework as one of the principle mechanisms for intervention. Population mental health needs were addressed by investment in infrastructure and services capacity among small and medium sized non-profit organizations working in disaster-impacted, low resource settings.

17 CFR 3.30 - Current address for purpose of delivery of communications from the Commission or the National...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Current address for purpose of... Current address for purpose of delivery of communications from the Commission or the National Futures Association. (a) The address of each registrant, applicant for registration and principal, as submitted on the...

Traversing the Skin Barrier with Nano-emulsions.

PubMed

Burger, Cornel; Shahzad, Yasser; Brummer, Alicia; Gerber, Minja; du Plessis, Jeanetta

2017-01-01

In recent years, colloidal delivery systems based on nano-emulsion are gaining popularity; being used for encapsulation and delivery of many drugs. This review therefore aims at summarizing various methods of nano-emulsion formulation and their use as a topical and transdermal delivery vehicle for a number of active pharmaceutical ingredients from different pharmacological classes. This article represents a systematic review of nano-emulsions for topical and transdermal drug delivery. A vast literature was searched and critically analysed. Nano-emulsions are thermokinetically stable dispersion systems, which have been used in topical and transdermal delivery of a number of pharmaceutically active compounds. Nano-emulsions have a narrow droplet size range with tuneable surface properties, which make them an ideal delivery vehicle. Nanoemulsions have a number of advantages over conventional emulsions, including easy preparation using various low and high energy methods, optical transparency, high solubilisation capacity, high stability to droplet aggregation and the ability to penetrate the skin; thus allowing the transdermal delivery of drugs. This review indicated that nano-emulsions are promising vehicle for entrapping various drugs and are suitable for traversing the skin barrier for systemic effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Health sector decentralization and local decision-making: Decision space, institutional capacities and accountability in Pakistan.

PubMed

Bossert, Thomas John; Mitchell, Andrew David

2011-01-01

Health sector decentralization has been widely adopted to improve delivery of health services. While many argue that institutional capacities and mechanisms of accountability required to transform decentralized decision-making into improvements in local health systems are lacking, few empirical studies exist which measure or relate together these concepts. Based on research instruments administered to a sample of 91 health sector decision-makers in 17 districts of Pakistan, this study analyzes relationships between three dimensions of decentralization: decentralized authority (referred to as "decision space"), institutional capacities, and accountability to local officials. Composite quantitative indicators of these three dimensions were constructed within four broad health functions (strategic and operational planning, budgeting, human resources management, and service organization/delivery) and on an overall/cross-function basis. Three main findings emerged. First, district-level respondents report varying degrees of each dimension despite being under a single decentralization regime and facing similar rules across provinces. Second, within dimensions of decentralization-particularly decision space and capacities-synergies exist between levels reported by respondents in one function and those reported in other functions (statistically significant coefficients of correlation ranging from ρ=0.22 to ρ=0.43). Third, synergies exist across dimensions of decentralization, particularly in terms of an overall indicator of institutional capacities (significantly correlated with both overall decision space (ρ=0.39) and accountability (ρ=0.23)). This study demonstrates that decentralization is a varied experience-with some district-level officials making greater use of decision space than others and that those who do so also tend to have more capacity to make decisions and are held more accountable to elected local officials for such choices. These findings suggest that Pakistan's decentralization policy should focus on synergies among dimensions of decentralization to encouraging more use of de jure decision space, work toward more uniform institutional capacity, and encourage greater accountability to local elected officials. Copyright © 2010 Elsevier Ltd. All rights reserved.

Medical cannabis use in Canada: vapourization and modes of delivery.

PubMed

Shiplo, Samantha; Asbridge, Mark; Leatherdale, Scott T; Hammond, David

2016-10-29

The mode of medical cannabis delivery-whether cannabis is smoked, vapourized, or consumed orally-may have important implications for its therapeutic efficacy and health risks. However, there is very little evidence on current patterns of use among Canadian medical cannabis users, particularly with respect to modes of delivery. The current study examined modes of medical cannabis delivery following regulatory changes in 2014 governing how Canadians access medical cannabis. A total of 364 approved adult Canadian medical cannabis users completed an online cross-sectional survey between April and June 2015. The survey examined patterns of medical cannabis use, modes of delivery used, and reasons for use. Participants were recruited through a convenience sample from nine Health Canada licensed producers. Using a vapourizer was the most popular mode of delivery for medical cannabis (53 %), followed by smoking a joint (47 %). The main reason for using a vapourizer was to reduce negative health consequences associated with smoking. A majority of current vapourizer users reported using a portable vapourizer (67.2 %), followed by a stationary vapourizer (41.7 %), and an e-cigarette or vape pen (19.3 %). Current use of a vapourizer was associated with fewer respiratory symptoms (AOR = 1.28, 95 % CI 1.05-1.56, p = 0.01). The findings suggest an increase in the popularity of vapourizers as the primary mode of delivery among approved medical users. Using vapourizers has the potential to prevent some of the adverse respiratory health consequences associated with smoking and may serve as an effective harm reduction method. Monitoring implications of such current and future changes to medical cannabis regulations may be beneficial to policymakers.

Assessment of current AASHTO LRFD methods for static pile capacity analysis in Rhode Island soils.

DOT National Transportation Integrated Search

2013-07-01

This report presents an assessment of current AASHTO LRFD methods for static pile capacity analysis in Rhode : Island soils. Current static capacity methods and associated resistance factors are based on pile load test data in sands : and clays. Some...

Institutional capacity for health systems research in East and Central Africa schools of public health: enhancing capacity to design and implement teaching programs.

PubMed

Nangami, Mabel N; Rugema, Lawrence; Tebeje, Bosena; Mukose, Aggrey

2014-06-02

The role of health systems research (HSR) in informing and guiding national programs and policies has been increasingly recognized. Yet, many universities in sub-Saharan African countries have relatively limited capacity to teach HSR. Seven schools of public health (SPHs) in East and Central Africa undertook an HSR institutional capacity assessment, which included a review of current HSR teaching programs. This study determines the extent to which SPHs are engaged in teaching HSR-relevant courses and assessing their capacities to effectively design and implement HSR curricula whose graduates are equipped to address HSR needs while helping to strengthen public health policy. This study used a cross-sectional study design employing both quantitative and qualitative approaches. An organizational profile tool was administered to senior staff across the seven SPHs to assess existing teaching programs. A self-assessment tool included nine questions relevant to teaching capacity for HSR curricula. The analysis triangulates the data, with reflections on the responses from within and across the seven SPHs. Proportions and average of values from the Likert scale are compared to determine strengths and weaknesses, while themes relevant to the objectives are identified and clustered to elicit in-depth interpretation. None of the SPHs offer an HSR-specific degree program; however, all seven offer courses in the Master of Public Health (MPH) degree that are relevant to HSR. The general MPH curricula partially embrace principles of competency-based education. Different strengths in curricula design and staff interest in HSR at each SPH were exhibited but a number of common constraints were identified, including out-of-date curricula, face-to-face delivery approaches, inadequate staff competencies, and limited access to materials. Opportunities to align health system priorities to teaching programs include existing networks. Each SPH has key strengths that can be leveraged to design and implement HSR teaching curricula. We propose networking for standardizing HSR curricula competencies, institutionalizing sharing of teaching resources, creating an HSR eLearning platform to expand access, regularly reviewing HSR teaching content to infuse competency-based approaches, and strengthening staff capacity to deliver such curricula.

Health research capacity building in Georgia: a case-based needs assessment.

PubMed

Squires, A; Chitashvili, T; Djibuti, M; Ridge, L; Chyun, D

2017-06-01

Research capacity building in the health sciences in low- and middle-income countries (LMICs) has typically focused on bench-science capacity, but research examining health service delivery and health workforce is equally necessary to determine the best ways to deliver care. The Republic of Georgia, formerly a part of the Soviet Union, has multiple issues within its healthcare system that would benefit from expended research capacity, but the current research environment needs to be explored prior to examining research-focused activities. The purpose of this project was to conduct a needs assessment focused on developing research capacity in the Republic of Georgia with an emphasis on workforce and network development. A case study approach guided by a needs assessment format. We conducted in-country, informal, semi-structured interviews in English with key informants and focus groups with faculty, students, and representatives of local non-governmental organizations. Purposive and snowball sampling approaches were used to recruit participants, with key informant interviews scheduled prior to arrival in country. Documents relevant to research capacity building were also included. Interview results were coded via content analysis. Final results were organized into a SWOT (strengths, weaknesses, opportunities, threat) analysis format, with the report shared with participants. There is widespread interest among students and faculty in Georgia around building research capacity. Lack of funding was identified by many informants as a barrier to research. Many critical research skills, such as proposal development, qualitative research skills, and statistical analysis, were reported as very limited. Participants expressed concerns about the ethics of research, with some suggesting that research is undertaken to punish or 'expose' subjects. However, students and faculty are highly motivated to improve their skills, are open to a variety of learning modalities, and have research priorities aligned with Georgian health needs. This study's findings indicate that while the Georgian research infrastructure needs further development, Georgian students and faculty are eager to supplement its gaps by improving their own skills. These findings are consistent with those seen in other developing country contexts. Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Institutional capacity for health systems research in East and Central Africa schools of public health: enhancing capacity to design and implement teaching programs

PubMed Central

2014-01-01

Background The role of health systems research (HSR) in informing and guiding national programs and policies has been increasingly recognized. Yet, many universities in sub-Saharan African countries have relatively limited capacity to teach HSR. Seven schools of public health (SPHs) in East and Central Africa undertook an HSR institutional capacity assessment, which included a review of current HSR teaching programs. This study determines the extent to which SPHs are engaged in teaching HSR-relevant courses and assessing their capacities to effectively design and implement HSR curricula whose graduates are equipped to address HSR needs while helping to strengthen public health policy. Methods This study used a cross-sectional study design employing both quantitative and qualitative approaches. An organizational profile tool was administered to senior staff across the seven SPHs to assess existing teaching programs. A self-assessment tool included nine questions relevant to teaching capacity for HSR curricula. The analysis triangulates the data, with reflections on the responses from within and across the seven SPHs. Proportions and average of values from the Likert scale are compared to determine strengths and weaknesses, while themes relevant to the objectives are identified and clustered to elicit in-depth interpretation. Results None of the SPHs offer an HSR-specific degree program; however, all seven offer courses in the Master of Public Health (MPH) degree that are relevant to HSR. The general MPH curricula partially embrace principles of competency-based education. Different strengths in curricula design and staff interest in HSR at each SPH were exhibited but a number of common constraints were identified, including out-of-date curricula, face-to-face delivery approaches, inadequate staff competencies, and limited access to materials. Opportunities to align health system priorities to teaching programs include existing networks. Conclusions Each SPH has key strengths that can be leveraged to design and implement HSR teaching curricula. We propose networking for standardizing HSR curricula competencies, institutionalizing sharing of teaching resources, creating an HSR eLearning platform to expand access, regularly reviewing HSR teaching content to infuse competency-based approaches, and strengthening staff capacity to deliver such curricula. PMID:24888353

Building systemic capacity for nutrition: training towards a professionalised workforce for Africa.

PubMed

Ellahi, Basma; Annan, Reginald; Sarkar, Swrajit; Amuna, Paul; Jackson, Alan A

2015-11-01

The fundamental role played by good nutrition in enabling personal, social and economic development is now widely recognised as presenting a fundamental global challenge that has to be addressed if major national and international problems are to be resolved in the coming decades. The recent focus provided by the Millennium Development Goals and the Scaling-Up-Nutrition (SUN) movement has been towards reducing the extent of nutrition-related malnutrition in high-burden countries. This has served to emphasise that there is a problem of inadequate professional capacity in nutrition that is sufficiently widespread to severely limit all attempts at the effective delivery and sustainability of nutrition-related and nutrition-enabling interventions that have impact at scale. Many high-burden countries are in sub-Saharan Africa where there is a high dependency on external technical support to address nutrition-related problems. We have sought to explore the nature and magnitude of the capacity needs with a particular focus on achieving levels of competency within standardised professional pre-service training which is fit-for-purpose to meet the objectives within the SUN movement in Africa. We review our experience of engaging with stakeholders through workshops, a gap analysis of the extent of the problem to be addressed, and a review of current efforts in Africa to move the agenda forward. We conclude that there are high aspirations but severely limited human resource and capacity for training that is fit-for-purpose at all skill levels in nutrition-related subjects in Africa. There are no structured or collaborative plans within professional groups to address the wide gap between what is currently available, the ongoing needs and the future expectations for meeting local technical and professional capability. Programmatic initiatives encouraged by agencies and other external players, will need to be matched by improved local capabilities to address the serious efforts required to meet the needs for sustained improvements related to SUN in high-burden countries. Importantly, there are pockets of effort which need to be encouraged within a context in which experience can be shared and mutual support provided.

Current application of phytocompound-based nanocosmeceuticals for beauty and skin therapy.

PubMed

Ganesan, Palanivel; Choi, Dong-Kug

2016-01-01

Phytocompounds have been used in cosmeceuticals for decades and have shown potential for beauty applications, including sunscreen, moisturizing and antiaging, and skin-based therapy. The major concerns in the usage of phyto-based cosmeceuticals are lower penetration and high compound instability of various cosmetic products for sustained and enhanced compound delivery to the beauty-based skin therapy. To overcome these disadvantages, nanosized delivery technologies are currently in use for sustained and enhanced delivery of phyto-derived bioactive compounds in cosmeceutical sectors and products. Nanosizing of phytocompounds enhances the aseptic feel in various cosmeceutical products with sustained delivery and enhanced skin protecting activities. Solid lipid nanoparticles, transfersomes, ethosomes, nanostructured lipid carriers, fullerenes, and carbon nanotubes are some of the emerging nanotechnologies currently in use for their enhanced delivery of phytocompounds in skin care. Aloe vera, curcumin, resveratrol, quercetin, vitamins C and E, genistein, and green tea catechins were successfully nanosized using various delivery technologies and incorporated in various gels, lotions, and creams for skin, lip, and hair care for their sustained effects. However, certain delivery agents such as carbon nanotubes need to be studied for their roles in toxicity. This review broadly focuses on the usage of phytocompounds in various cosmeceutical products, nanodelivery technologies used in the delivery of phytocompounds to various cosmeceuticals, and various nanosized phytocompounds used in the development of novel nanocosmeceuticals to enhance skin-based therapy.

Current application of phytocompound-based nanocosmeceuticals for beauty and skin therapy

PubMed Central

Ganesan, Palanivel; Choi, Dong-Kug

2016-01-01

Phytocompounds have been used in cosmeceuticals for decades and have shown potential for beauty applications, including sunscreen, moisturizing and antiaging, and skin-based therapy. The major concerns in the usage of phyto-based cosmeceuticals are lower penetration and high compound instability of various cosmetic products for sustained and enhanced compound delivery to the beauty-based skin therapy. To overcome these disadvantages, nanosized delivery technologies are currently in use for sustained and enhanced delivery of phyto-derived bioactive compounds in cosmeceutical sectors and products. Nanosizing of phytocompounds enhances the aseptic feel in various cosmeceutical products with sustained delivery and enhanced skin protecting activities. Solid lipid nanoparticles, transfersomes, ethosomes, nanostructured lipid carriers, fullerenes, and carbon nanotubes are some of the emerging nanotechnologies currently in use for their enhanced delivery of phytocompounds in skin care. Aloe vera, curcumin, resveratrol, quercetin, vitamins C and E, genistein, and green tea catechins were successfully nanosized using various delivery technologies and incorporated in various gels, lotions, and creams for skin, lip, and hair care for their sustained effects. However, certain delivery agents such as carbon nanotubes need to be studied for their roles in toxicity. This review broadly focuses on the usage of phytocompounds in various cosmeceutical products, nanodelivery technologies used in the delivery of phytocompounds to various cosmeceuticals, and various nanosized phytocompounds used in the development of novel nanocosmeceuticals to enhance skin-based therapy. PMID:27274231

The LIFEspan model of transitional rehabilitative care for youth with disabilities: healthcare professionals' perspectives on service delivery.

PubMed

Hamdani, Yani; Proulx, Meghann; Kingsnorth, Shauna; Lindsay, Sally; Maxwell, Joanne; Colantonio, Angela; Macarthur, Colin; Bayley, Mark

2014-01-01

LIFEspan is a service delivery model of continuous coordinated care developed and implemented by a cross-organization partnership between a pediatric and an adult rehabilitation hospital. Previous work explored enablers and barriers to establishing the partnership service. This paper examines healthcare professionals' (HCPs') experiences of 'real world' service delivery aimed at supporting transitional rehabilitative care for youth with disabilities. This qualitative study - part of an ongoing mixed method longitudinal study - elicited HCPs' perspectives on their experiences of LIFEspan service delivery through in-depth interviews. Data were categorized into themes of service delivery activities, then interpreted from the lens of a service integration/coordination framework. Five main service delivery themes were identified: 1) addressing youth's transition readiness and capacities; 2) shifting responsibility for healthcare management from parents to youth; 3) determining services based on organizational resources; 4) linking between pediatric and adult rehabilitation services; and, 5) linking with multi-sector services. LIFEspan contributed to service delivery activities that coordinated care for youth and families and integrated inter-hospital services. However, gaps in service integration with primary care, education, social, and community services limited coordinated care to the rehabilitation sector. Recommendations are made to enhance service delivery using a systems/sector-based approach.

Calcium silicate-based drug delivery systems.

PubMed

Zhu, Ying-Jie; Guo, Xiao-Xuan; Sham, Tsun-Kong

2017-02-01

Compared with other inorganic materials such as silica, metal oxides, noble metals and carbon, calcium silicate-based materials, especially nanostructured calcium silicate materials, have high biocompatibility, bioactivity and biodegradability, high specific surface area, nanoporous/hollow structure, high drug-loading capacity, pH-responsive drug release behavior and desirable drug release properties, and thus they are promising for the application in drug delivery. Calcium silicate-based drug delivery systems have a long drug-release time, which can significantly prolong the therapeutic effect of drugs. Another advantage of calcium silicate-based drug delivery systems is their pH-responsive drug release property, which can act as an ideal platform for targeted drug delivery. Areas covered: In recent years, studies have been carried out on calcium silicate-based drug delivery systems, and important results and insights have been documented. This article is not intended to offer a comprehensive review on the research on calcium silicate-based drug delivery systems, but presents some examples reported in the literature, and includes new insights obtained by tracking the interactions between drug molecules and calcium silicate carriers on the molecular level using the synchrotron-based X-ray spectroscopy. Expert opinion: Finally, our opinions on calcium silicate-based drug delivery systems are provided, and several research directions for the future studies are proposed.

Imaging modalities for the in vivo surveillance of mesenchymal stromal cells.

PubMed

Hossain, Mohammad Ayaz; Chowdhury, Tina; Bagul, Atul

2015-11-01

Bone marrow stromal cells exist as mesenchymal stromal cells (MSCs) and have the capacity to differentiate into multiple tissue types when subjected to appropriate culture conditions. This property of MSCs creates therapeutic opportunities in regenerative medicine for the treatment of damage to neural, cardiac and musculoskeletal tissues or acute kidney injury. The prerequisite for successful cell therapy is delivery of cells to the target tissue. Assessment of therapeutic outcomes utilize traditional methods to examine cell function of MSC populations involving routine biochemical or histological analysis for cell proliferation, protein synthesis and gene expression. However, these methods do not provide sufficient spatial and temporal information. In vivo surveillance of MSC migration to the site of interest can be performed through a variety of imaging modalities such as the use of radiolabelling, fluc protein expression bioluminescence imaging and paramagnetic nanoparticle magnetic resonance imaging. This review will outline the current methods of in vivo surveillance of exogenously administered MSCs in regenerative medicine while addressing potential technological developments. Furthermore, nanoparticles and microparticles for cellular labelling have shown that migration of MSCs can be spatially and temporally monitored. In vivo surveillance therefore permits time-stratified assessment in animal models without disruption of the target organ. In vivo tracking of MSCs is non-invasive, repeatable and non-toxic. Despite the excitement that nanoparticles for tracking MSCs offer, delivery methods are difficult because of the challenges with imaging three-dimensional systems. The current advances and growth in MSC research, is likely to provide a wealth of evidence overcoming these issues. Copyright © 2014 John Wiley & Sons, Ltd.

Designing and developing suppository formulations for anti-HIV drug delivery.

PubMed

Ham, Anthony S; Buckheit, Robert W

2017-08-01

Despite a long history of use for rectal and vaginal drug delivery, the current worldwide market for suppositories is limited primarily due to a lack of user acceptability. Therefore, virtually no rational pharmaceutical development of antiviral suppositories has been performed. However, suppositories offer several advantages over other antiviral dosage forms. Current suppository designs have integrated active pharmaceutical ingredients into existing formulation designs without optimization. As such, emerging suppository development has been focused on improving upon the existing classical design to enhance drug delivery and is poised to open suppository drug delivery to a broader range of drugs, including antiretroviral products. Thus, with continuing research into rational suppository design and development, there is significant potential for antiretroviral suppository drug delivery.

Enabling Data Access for Environmental Monitoring: SERVIR West Africa

NASA Astrophysics Data System (ADS)

Yetman, G.; de Sherbinin, A. M.

2017-12-01

SERVIR is a join effort between NASA and the U.S. Agency for International Development to form regional partnerships and bring satellite-based earth monitoring and geographic information technologies to bear on environmental issues. The recently established SERVIR node for West Africa aims to "connect space to villages" and enable response to environmental change at the national and local level through partnering with a network of organizations in the region. Comprehensive services—data streams, analysis methods and algorithms, and information products for decision making—to support environmental monitoring of five critical issues identified by West African network members are being designed and developed: ephemeral water, charcoal production, locusts, groundwater, and land use/land cover change. Additionally, climate change information is critical for planning and context in each of these issues. The selection of data and methods is a collaborative effort, with experts in the region working with experts at NASA and the scientific community to best meet information monitoring requirements. Design and delivery of these services requires capacity development in a number of areas, including best practices in data management, analysis methods for combining multiple data streams, and information technology infrastructure. Two research centers at Columbia University are implementing partners for SERVIR West Africa, acting to support capacity development in network members through a combination of workshops, training, and implementation of technologies in the region. The presentation will focus on efforts by these centers to assess current capabilities and improve capacity through gathering requirements, system design, technology selection, technology deployment, training, and workshops.

Private sector participation in domestic waste management in informal settlements in Lagos, Nigeria.

PubMed

Opoko, Akunnaya P; Oluwatayo, Adedapo A

2016-12-01

Lagos is one of the fastest growing cities in Africa, which is grappling with the challenges of poorly managed urbanisation. With an estimated population of about 17.5 million, solid waste management is one of the most pressing environmental challenges currently faced in the city. It is estimated that more than 9071847.4kg of urban waste is generated every day in the city. The city lacks the capacity to deal with such magnitude of waste. Consequently, the city has involved the private sector (private sector participation) in its waste management drive. This article examines the effectiveness of this public-private sector collaboration model in waste management in informal settlements in Lagos using empirical data. Major findings of the article include the irregularity of waste collection owing to a poor road network, an inadequate transport infrastructure and the desire to maximise profit, as well as poor waste handling and disposal methods by the private sector participation operators who are not chosen based on competence and capacity to perform. Another major finding is the lack of cooperation from residents evidenced in non-payment of bills and poor packaging of wastes, resulting in wastes being littered. The article concludes on the need to restructure the scheme through proper sensitisation of residents, selection of operators with demonstrable delivery capacity and provision of a well-maintained road network to facilitate access of operators to settlements. © The Author(s) 2016.

Regenerative Therapies for Central Nervous System Diseases: a Biomaterials Approach

PubMed Central

Tam, Roger Y; Fuehrmann, Tobias; Mitrousis, Nikolaos; Shoichet, Molly S

2014-01-01

The central nervous system (CNS) has a limited capacity to spontaneously regenerate following traumatic injury or disease, requiring innovative strategies to promote tissue and functional repair. Tissue regeneration strategies, such as cell and/or drug delivery, have demonstrated promising results in experimental animal models, but have been difficult to translate clinically. The efficacy of cell therapy, which involves stem cell transplantation into the CNS to replace damaged tissue, has been limited due to low cell survival and integration upon transplantation, while delivery of therapeutic molecules to the CNS using conventional methods, such as oral and intravenous administration, have been limited by diffusion across the blood–brain/spinal cord-barrier. The use of biomaterials to promote graft survival and integration as well as localized and sustained delivery of biologics to CNS injury sites is actively being pursued. This review will highlight recent advances using biomaterials as cell- and drug-delivery vehicles for CNS repair. PMID:24002187

Ligand-based targeted therapy: a novel strategy for hepatocellular carcinoma

PubMed Central

Li, Min; Zhang, Weiyue; Wang, Birong; Gao, Yang; Song, Zifang; Zheng, Qi Chang

2016-01-01

Hepatocellular carcinoma (HCC) is the most common primary liver cancer with high morbidity and mortality worldwide. Chemotherapy is recommended to patients with intermediate or advanced stage cancer. However, the conventional chemotherapy yields low desired response rates due to multidrug resistance, fast clearance rate, nonspecific delivery, severe side effects, low drug concentration in cancer cells, and so on. Nanoparticle-mediated targeted drug delivery system can surmount the aforementioned obstacles through enhanced permeability and retention effect and active targeting as a novel approach of therapeutics for HCC in recent years. The active targeting is triggered by ligands on the delivery system, which recognize with and internalize into hepatoma cells with high specificity and efficiency. This review focuses on the latest targeted delivery systems for HCC and summarizes the ligands that can enhance the capacity of active targeting, to provide some insight into future research in nanomedicine for HCC. PMID:27920520

Nanoparticles engineered to bind cellular motors for efficient delivery.

PubMed

Dalmau-Mena, Inmaculada; Del Pino, Pablo; Pelaz, Beatriz; Cuesta-Geijo, Miguel Ángel; Galindo, Inmaculada; Moros, María; de la Fuente, Jesús M; Alonso, Covadonga

2018-03-30

Dynein is a cytoskeletal molecular motor protein that transports cellular cargoes along microtubules. Biomimetic synthetic peptides designed to bind dynein have been shown to acquire dynamic properties such as cell accumulation and active intra- and inter-cellular motion through cell-to-cell contacts and projections to distant cells. On the basis of these properties dynein-binding peptides could be used to functionalize nanoparticles for drug delivery applications. Here, we show that gold nanoparticles modified with dynein-binding delivery sequences become mobile, powered by molecular motor proteins. Modified nanoparticles showed dynamic properties, such as travelling the cytosol, crossing intracellular barriers and shuttling the nuclear membrane. Furthermore, nanoparticles were transported from one cell to another through cell-to-cell contacts and quickly spread to distant cells through cell projections. The capacity of these motor-bound nanoparticles to spread to many cells and increasing cellular retention, thus avoiding losses and allowing lower dosage, could make them candidate carriers for drug delivery.

Towards magnetic-enhanced cellular uptake, MRI and chemotherapeutics delivery by magnetic mesoporous silica nanoparticles.

PubMed

Liu, Qian; Zhang, Jixi; Xia, Weiliang; Gu, Hongchen

2012-10-01

A type of nanoparticle with three functional modalities was prepared with the aim of providing a multifunctional drug delivery system. The nanoparticle was 50 nm in size, with 2.7 nm mesopores and a magnetic nanocrystal core, which was further doped with FITC to enable the tracking of cellular uptake. We demonstrated that the internalization of the nanoparticles in tumor cells could be enhanced by applying an external magnetic field and furthermore, this kind of nanoparticle could be used in magnetic targeted drug delivery. With high transverse relaxivity, the magnetic nanoparticles shortened proton relaxation time and induced high magnetic resonance imaging contrast in tumor cells. Studies on anticancer drug loading and delivery capacity of anticancer drugs also showed that this type of nanoparticles could load water-soluble doxorubicin, and produce a prominent inhibitive effect against tumor cells. Taken together, the presented nanoparticles could become a promising agent in cancer theranostics.

MicroRNAs in glioblastoma multiforme pathogenesis and therapeutics.

PubMed

Shea, Amanda; Harish, Varsha; Afzal, Zainab; Chijioke, Juliet; Kedir, Habib; Dusmatova, Shahnoza; Roy, Arpita; Ramalinga, Malathi; Harris, Brent; Blancato, Jan; Verma, Mukesh; Kumar, Deepak

2016-08-01

Glioblastoma multiforme (GBM) is the most common and lethal cancer of the adult brain, remaining incurable with a median survival time of only 15 months. In an effort to identify new targets for GBM diagnostics and therapeutics, recent studies have focused on molecular phenotyping of GBM subtypes. This has resulted in mounting interest in microRNAs (miRNAs) due to their regulatory capacities in both normal development and in pathological conditions such as cancer. miRNAs have a wide range of targets, allowing them to modulate many pathways critical to cancer progression, including proliferation, cell death, metastasis, angiogenesis, and drug resistance. This review explores our current understanding of miRNAs that are differentially modulated and pathologically involved in GBM as well as the current state of miRNA-based therapeutics. As the role of miRNAs in GBM becomes more well understood and novel delivery methods are developed and optimized, miRNA-based therapies could provide a critical step forward in cancer treatment. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Letter from America: UK and US state-funded dental provision.

PubMed

Currie, R B; Pretty, I A; Tickle, M; Maupomé, G

2012-12-01

Current UK and US economic conditions have re-focussed attention on the need to deliver dental care with limited finance and resources. This raises hard questions determining which services will be offered and what they should achieve to satisfy public demands and needs. We consider impending dental health reforms in the US and UK within the context of contemporary experiences to identify issues and delivery goals for the two nations. The paper provides a brief history and background of the development of social dental care models in the UK and US, highlighting some differences in state-funded delivery of dental care. SHIFTING DEMAND: From the 1950s, demand for dental treatment has increased and acquired a more complex composition growing from predominantly surgical and restorative treatment to encompass preventive care and cosmetic services. PRIORITISING CARE ACCORDING TO NEED: Despite improvements in general health and technology, inequalities in access and utilisation of dental care are still experienced, primarily by groups with low socio-economic status. DELIVERY: BALANCING RESOURCES, DEMAND AND NEED: In developing and delivering reform agendas, much can be learned from previous policy interventions. Pressures of cost, coverage, and capacity, besides demand versus need must be carefully considered and balanced to deliver quality service and value for users and taxpayers. Ethical and moral consideration should be given to making services needs-driven to address high treatment requirements rather than the high care demands of the worried well. This challenge brings the additional political pressure of convincing many of the voters (and subsequent complainers) that their demands may be less important than the needs of others.

A novel approach for targeted delivery to motoneurons using cholera toxin-B modified protocells

PubMed Central

Gonzalez Porras, Maria A.; Durfee, Paul N.; Gregory, Ashley M.; Sieck, Gary C.; Brinker, C. Jeffrey; Mantilla, Carlos B.

2017-01-01

Background Trophic interactions between muscle fibers and motoneurons at the neuromuscular junction (NMJ) play a critical role in determining motor function throughout development, ageing, injury, or disease. Treatment of neuromuscular disorders is hindered by the inability to selectively target motoneurons with pharmacological and genetic interventions. New method We describe a novel delivery system to motoneurons using mesoporous silica nanoparticles encapsulated within a lipid bilayer (protocells) and modified with the atoxic subunit B of the cholera toxin (CTB) that binds to gangliosides present on neuronal membranes. Results CTB modified protocells showed significantly greater motoneuron uptake compared to unmodified protocells after 24 h of treatment (60% vs. 15%, respectively). CTB-protocells showed specific uptake by motoneurons compared to muscle cells and demonstrated cargo release of a surrogate drug. Protocells showed a lack of cytotoxicity and unimpaired cellular proliferation. In isolated diaphragm muscle-phrenic nerve preparations, preferential axon terminal uptake of CTB-modified protocells was observed compared to uptake in surrounding muscle tissue. A larger proportion of axon terminals displayed uptake following treatment with CTB-protocells compared to unmodified protocells (40% vs. 6%, respectively). Comparison with existing method(s) Current motoneuron targeting strategies lack the functionality to load and deliver multiple cargos. CTB-protocells capitalizes on the advantages of liposomes and mesoporous silica nanoparticles allowing a large loading capacity and cargo release. The ability of CTB-protocells to target motoneurons at the NMJ confers a great advantage over existing methods. Conclusions CTB-protocells constitute a viable targeted motoneuron delivery system for drugs and genes facilitating various therapies for neuromuscular diseases. PMID:27641118

A novel approach for targeted delivery to motoneurons using cholera toxin-B modified protocells.

PubMed

Gonzalez Porras, Maria A; Durfee, Paul N; Gregory, Ashley M; Sieck, Gary C; Brinker, C Jeffrey; Mantilla, Carlos B

2016-11-01

Trophic interactions between muscle fibers and motoneurons at the neuromuscular junction (NMJ) play a critical role in determining motor function throughout development, ageing, injury, or disease. Treatment of neuromuscular disorders is hindered by the inability to selectively target motoneurons with pharmacological and genetic interventions. We describe a novel delivery system to motoneurons using mesoporous silica nanoparticles encapsulated within a lipid bilayer (protocells) and modified with the atoxic subunit B of the cholera toxin (CTB) that binds to gangliosides present on neuronal membranes. CTB modified protocells showed significantly greater motoneuron uptake compared to unmodified protocells after 24h of treatment (60% vs. 15%, respectively). CTB-protocells showed specific uptake by motoneurons compared to muscle cells and demonstrated cargo release of a surrogate drug. Protocells showed a lack of cytotoxicity and unimpaired cellular proliferation. In isolated diaphragm muscle-phrenic nerve preparations, preferential axon terminal uptake of CTB-modified protocells was observed compared to uptake in surrounding muscle tissue. A larger proportion of axon terminals displayed uptake following treatment with CTB-protocells compared to unmodified protocells (40% vs. 6%, respectively). Current motoneuron targeting strategies lack the functionality to load and deliver multiple cargos. CTB-protocells capitalizes on the advantages of liposomes and mesoporous silica nanoparticles allowing a large loading capacity and cargo release. The ability of CTB-protocells to target motoneurons at the NMJ confers a great advantage over existing methods. CTB-protocells constitute a viable targeted motoneuron delivery system for drugs and genes facilitating various therapies for neuromuscular diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

The Doctoral Degree in Dental Hygiene: Creating New Oral Healthcare Paradigms.

PubMed

Gurenlian, JoAnn R; Rogo, Ellen J; Spolarich, Ann Eshenaur

2016-06-01

Doctoral dental hygiene education would prepare scholars and leaders to improve population health through changes in oral health policy and delivery. Discussions about doctoral education in dental hygiene have centered on the need to create a cadre of dental hygiene researchers and scholars who will expand the body of knowledge for the profession. It has been proposed that scholars are needed to lead the development of theory and disseminate knowledge unique to the discipline of dental hygiene. Transformation to doctoral education is not a new trend as many other health care disciplines have already implemented curricular models, establishing the doctoral degree for entry level into practice. The Institute of Medicine has called for the exploration of new models for care delivery. Dental hygienists need to be prepared with leadership skills enabling them to participate and lead interprofessional teams and develop policies designed to improve the delivery of oral health care services to enhance population health. Current educational models do not adequately prepare dental hygienists to serve in this capacity. The purpose of this article is to present 2 models of doctoral education for dental hygiene that will illustrate how dental hygienists can be better prepared as scholars and leaders for the profession. These proposed models of doctoral education in dental hygiene present a paradigm shift in dental hygiene education. As with other disciplines that have evolved, both academically and professionally, dental hygiene will be positioned to achieve the hallmark of professional status with this terminal degree. Copyright © 2016 Elsevier Inc. All rights reserved.

Dental mesenchymal stem cells encapsulated in an alginate hydrogel co-delivery microencapsulation system for cartilage regeneration.

PubMed

Moshaverinia, Alireza; Xu, Xingtian; Chen, Chider; Akiyama, Kentaro; Snead, Malcolm L; Shi, Songtao

2013-12-01

Dental-derived mesenchymal stem cells (MSCs) are promising candidates for cartilage regeneration, with a high capacity for chondrogenic differentiation. This property helps make dental MSCs an advantageous therapeutic option compared to current treatment modalities. The MSC delivery vehicle is the principal determinant for the success of MSC-mediated cartilage regeneration therapies. The objectives of this study were to: (1) develop a novel co-delivery system based on TGF-β1 loaded RGD-coupled alginate microspheres encapsulating periodontal ligament stem cells (PDLSCs) or gingival mesenchymal stem cells (GMSCs); and (2) investigate dental MSC viability and chondrogenic differentiation in alginate microspheres. The results revealed the sustained release of TGF-β1 from the alginate microspheres. After 4 weeks of chondrogenic differentiation in vitro, PDLSCs and GMSCs as well as human bone marrow mesenchymal stem cells (hBMMSCs) (as positive control) revealed chondrogenic gene expression markers (Col II and Sox-9) via qPCR, as well as matrix positively stained by Toluidine Blue and Safranin-O. In animal studies, ectopic cartilage tissue regeneration was observed inside and around the transplanted microspheres, confirmed by histochemical and immunofluorescent staining. Interestingly, PDLSCs showed more chondrogenesis than GMSCs and hBMMSCs (p<0.05). Taken together, these results suggest that RGD-modified alginate microencapsulating dental MSCs make a promising candidate for cartilage regeneration. Our results highlight the vital role played by the microenvironment, as well as value of presenting inductive signals for viability and differentiation of MSCs. Copyright © 2013 Acta Materialia Inc. All rights reserved.

Hybrid biosynthetic gene therapy vector development and dual engineering capacity.

PubMed

Jones, Charles H; Ravikrishnan, Anitha; Chen, Mingfu; Reddinger, Ryan; Kamal Ahmadi, Mahmoud; Rane, Snehal; Hakansson, Anders P; Pfeifer, Blaine A

2014-08-26

Genetic vaccines offer a treatment opportunity based upon successful gene delivery to specific immune cell modulators. Driving the process is the vector chosen for gene cargo packaging and subsequent delivery to antigen-presenting cells (APCs) capable of triggering an immune cascade. As such, the delivery process must successfully navigate a series of requirements and obstacles associated with the chosen vector and target cell. In this work, we present the development and assessment of a hybrid gene delivery vector containing biological and biomaterial components. Each component was chosen to design and engineer gene delivery separately in a complimentary and fundamentally distinct fashion. A bacterial (Escherichia coli) inner core and a biomaterial [poly(beta-amino ester)]-coated outer surface allowed the simultaneous application of molecular biology and polymer chemistry to address barriers associated with APC gene delivery, which include cellular uptake and internalization, phagosomal escape, and intracellular cargo concentration. The approach combined and synergized normally disparate vector properties and tools, resulting in increased in vitro gene delivery beyond individual vector components or commercially available transfection agents. Furthermore, the hybrid device demonstrated a strong, efficient, and safe in vivo humoral immune response compared with traditional forms of antigen delivery. In summary, the flexibility, diversity, and potential of the hybrid design were developed and featured in this work as a platform for multivariate engineering at the vector and cellular scales for new applications in gene delivery immunotherapy.

Transforming lipid-based oral drug delivery systems into solid dosage forms: an overview of solid carriers, physicochemical properties, and biopharmaceutical performance.

PubMed

Tan, Angel; Rao, Shasha; Prestidge, Clive A

2013-12-01

The diversity of lipid excipients available commercially has enabled versatile formulation design of lipid-based drug delivery systems for enhancing the oral absorption of poorly water-soluble drugs, such as emulsions, microemulsions, micelles, liposomes, niosomes and various self-emulsifying systems. The transformation of liquid lipid-based systems into solid dosage forms has been investigated for several decades, and has recently become a core subject of pharmaceutical research as solidification is regarded as viable means for stabilising lipid colloidal systems while eliminating stringent processing requirements associated with liquid systems. This review describes the types of pharmaceutical grade excipients (silica nanoparticle/microparticle, polysaccharide, polymer and protein-based materials) used as solid carriers and the current state of knowledge on the liquid-to-solid conversion approaches. Details are primarily focused on the solid-state physicochemical properties and redispersion capacity of various dry lipid-based formulations, and how these relate to the in vitro drug release and solubilisation, lipid carrier digestion and cell permeation performances. Numerous in vivo proof-of-concept studies are presented to highlight the viability of these dry lipid-based formulations. This review is significant in directing future research work in fostering translation of dry lipid-based formulations into clinical applications.

Nanolayer encapsulation of insulin-chitosan complexes improves efficiency of oral insulin delivery

PubMed Central

Song, Lei; Zhi, Zheng-liang; Pickup, John C

2014-01-01

Current oral insulin formulations reported in the literature are often associated with an unpredictable burst release of insulin in the intestine, which may increase the risk for problematic hypoglycemia. The aim of the study was to develop a solution based on a nanolayer encapsulation of insulin-chitosan complexes to afford sustained release after oral administration. Chitosan/heparin multilayer coatings were deposited onto insulin-chitosan microparticulate cores in the presence of poly(ethylene) glycol (PEG) in the precipitating and coating solutions. The addition of PEG improved insulin loading and minimized an undesirable loss of the protein resulting from redissolution. Nanolayer encapsulation and the formation of complexes enabled a superior loading capacity of insulin (>90%), as well as enhanced stability and 74% decreased solubility at acid pH in vitro, compared with nonencapsulated insulin. The capsulated insulin administered by oral gavage lowered fasting blood glucose levels by up to 50% in a sustained and dose-dependent manner and reduced postprandial glycemia in streptozotocin-induced diabetic mice without causing hypoglycemia. Nanolayer encapsulation reduced the possibility of rapid and erratic falls of blood glucose levels in animals. This technique represents a promising strategy to promote the intestinal absorption efficiency and release behavior of the hormone, potentially enabling an efficient and safe route for oral insulin delivery of insulin in diabetes management. PMID:24833901

Development of Multifunctional Magnetic Nanoparticles for Genetic Engineering and Tracking of Neural Stem Cells.

PubMed

Adams, Christopher; Israel, Liron Limor; Ostrovsky, Stella; Taylor, Arthur; Poptani, Harish; Lellouche, Jean-Paul; Chari, Divya

2016-04-06

Genetic modification of cell transplant populations and cell tracking ability are key underpinnings for effective cell therapies. Current strategies to achieve these goals utilize methods which are unsuitable for clinical translation because of related safety issues, and multiple protocol steps adding to cost and complexity. Multifunctional magnetic nanoparticles (MNPs) offering dual mode gene delivery and imaging contrast capacity offer a valuable tool in this context. Despite their key benefits, there is a critical lack of neurocompatible and multifunctional particles described for use with transplant populations for neurological applications. Here, a systematic screen of MNPs (using a core shown to cause contrast in magnetic resonance imaging (MRI)) bearing various surface chemistries (polyethylenimine (PEI) and oxidized PEI and hybrids of oxidized PEI/alginic acid, PEI/chitosan and PEI/polyamidoamine) is performed to test their ability to genetically engineer neural stem cells (NSCs; a cell population of high clinical relevance for central nervous system disorders). It is demonstrated that gene delivery to NSCs can be safely achieved using two of the developed formulations (PEI and oxPEI/alginic acid) when used in conjunction with oscillating magnetofection technology. After transfection, intracellular particles can be detected by histological procedures with labeled cells displaying contrast in MRI (for real time cell tracking). © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nanoengineering of vaccines using natural polysaccharides.

PubMed

Cordeiro, Ana Sara; Alonso, María José; de la Fuente, María

2015-11-01

Currently, there are over 70 licensed vaccines, which prevent the pathogenesis of around 30 viruses and bacteria. Nevertheless, there are still important challenges in this area, which include the development of more active, non-invasive, and thermo-resistant vaccines. Important biotechnological advances have led to safer subunit antigens, such as proteins, peptides, and nucleic acids. However, their limited immunogenicity has demanded potent adjuvants that can strengthen the immune response. Particulate nanocarriers hold a high potential as adjuvants in vaccination. Due to their pathogen-like size and structure, they can enhance immune responses by mimicking the natural infection process. Additionally, they can be tailored for non-invasive mucosal administration (needle-free vaccination), and control the delivery of the associated antigens to a specific location and for prolonged times, opening room for single-dose vaccination. Moreover, they allow co-association of immunostimulatory molecules to improve the overall adjuvant capacity. The natural and ubiquitous character of polysaccharides, together with their intrinsic immunomodulating properties, their biocompatibility, and biodegradability, justify their interest in the engineering of nanovaccines. In this review, we aim to provide a state-of-the-art overview regarding the application of nanotechnology in vaccine delivery, with a focus on the most recent advances in the development and application of polysaccharide-based antigen nanocarriers. Copyright © 2015 Elsevier Inc. All rights reserved.

Controlled Striatal DOPA Production From a Gene Delivery System in a Rodent Model of Parkinson's Disease.

PubMed

Cederfjäll, Erik; Broom, Lauren; Kirik, Deniz

2015-05-01

Conventional symptomatic treatment for Parkinson's disease (PD) with long-term L-3,4-dihydroxyphenylalanine (DOPA) is complicated with development of drug-induced side effects. In vivo viral vector-mediated gene expression encoding tyrosine hydroxylase (TH) and GTP cyclohydrolase 1 (GCH1) provides a drug delivery strategy of DOPA with distinct advantages over pharmacotherapy. Since the brain alterations made with current gene transfer techniques are irreversible, the therapeutic approaches taken to the clinic should preferably be controllable to match the needs of each individual during the course of their disease. We used a recently described tunable gene expression system based on the use of destabilized dihydrofolate reductase (DD) and generated a N-terminally coupled GCH1 enzyme (DD-GCH1) while the TH enzyme was constitutively expressed, packaged in adeno-associated viral (AAV) vectors. Expression of DD-GCH1 was regulated by the activating ligand trimethoprim (TMP) that crosses the blood-brain barrier. We show that the resulting intervention provides a TMP-dose-dependent regulation of DOPA synthesis that is closely linked to the magnitude of functional effects. Our data constitutes the first proof of principle for controlled reconstitution of dopamine capacity in the brain and suggests that such next-generation gene therapy strategies are now mature for preclinical development toward use in patients with PD.

Development of Sendai Virus Vectors and their Potential Applications in Gene Therapy and Regenerative Medicine

PubMed Central

Nakanishi, Mahito; Otsu, Makoto

2012-01-01

Gene delivery/expression vectors have been used as fundamental technologies in gene therapy since the 1980s. These technologies are also being applied in regenerative medicine as tools to reprogram cell genomes to a pluripotent state and to other cell lineages. Rapid progress in these new research areas and expectations for their translation into clinical applications have facilitated the development of more sophisticated gene delivery/expression technologies. Since its isolation in 1953 in Japan, Sendai virus (SeV) has been widely used as a research tool in cell biology and in industry, but the application of SeV as a recombinant viral vector has been investigated only recently. Recombinant SeV vectors have various unique characteristics, such as low pathogenicity, powerful capacity for gene expression and a wide host range. In addition, the cytoplasmic gene expression mediated by this vector is advantageous for applications, in that chromosomal integration of exogenous genes can be undesirable. In this review, we introduce a brief historical background on the development of recombinant SeV vectors and describe their current applications in gene therapy. We also describe the application of SeV vectors in advanced nuclear reprogramming and introduce a defective and persistent SeV vector (SeVdp) optimized for such reprogramming. PMID:22920683

Carbon nanotubes (CNTs) based advanced dermal therapeutics: current trends and future potential.

PubMed

Kuche, Kaushik; Maheshwari, Rahul; Tambe, Vishakha; Mak, Kit-Kay; Jogi, Hardi; Raval, Nidhi; Pichika, Mallikarjuna Rao; Kumar Tekade, Rakesh

2018-05-17

The search for effective and non-invasive delivery modules to transport therapeutic molecules across skin has led to the discovery of a number of nanocarriers (viz.: liposomes, ethosomes, dendrimers, etc.) in the last few decades. However, available literature suggests that these delivery modules face several issues including poor stability, low encapsulation efficiency, and scale-up hurdles. Recently, carbon nanotubes (CNTs) emerged as a versatile tool to deliver therapeutics across skin. Superior stability, high loading capacity, well-developed synthesis protocol as well as ease of scale-up are some of the reason for growing interest in CNTs. CNTs have a unique physical architecture and a large surface area with unique surface chemistry that can be tailored for vivid biomedical applications. CNTs have been thus largely engaged in the development of transdermal systems such as tuneable hydrogels, programmable nonporous membranes, electroresponsive skin modalities, protein channel mimetic platforms, reverse iontophoresis, microneedles, and dermal buckypapers. In addition, CNTs were also employed in the development of RNA interference (RNAi) based therapeutics for correcting defective dermal genes. This review expounds the state-of-art synthesis methodologies, skin penetration mechanism, drug liberation profile, loading potential, characterization techniques, and transdermal applications along with a summary on patent/regulatory status and future scope of CNT based skin therapeutics.

Cyclodextrin-based supramolecular systems for drug delivery: Recent progress and future perspective

PubMed Central

Zhang, Jianxiang; Ma, Peter X

2013-01-01

The excellent biocompatibility and unique inclusion capability as well as powerful functionalization capacity of cyclodextrins and their derivatives make them especially attractive for engineering novel functional materials for biomedical applications. There has been increasing interest recently to fabricate supramolecular systems for drug and gene delivery based on cyclodextrin materials. This review focuses on state of the art and recent advances in the construction of cyclodextrin-based assemblies and their applications for controlled drug delivery. First, we introduce cyclodextrin materials utilized for self-assembly. The fabrication technologies of supramolecular systems including nanoplatforms and hydrogels as well as their applications in nanomedicine and pharmaceutical sciences are then highlighted. At the end, the future directions of this field are discussed. PMID:23673149

Vocational technical and adult education: Status, trends and issues related to electronic delivery

NASA Technical Reports Server (NTRS)

Rothenberg, D.

1973-01-01

Data are analyzed, and trends and issues are discussed to provide information useful to the systems designer who wishes to identify and assess the opportunities for large scale electronic delivery in vocational/technical and adult education. Issues connected with vocational/technical education are investigated, with emphasis on those issues in the current spotlight which are relevant to the possibilities of electronic delivery. The current role of media is examined in vocational/technical instruction.

The change in capacity and service delivery at public and private hospitals in Turkey: a closer look at regional differences.

PubMed

Aksan, Hediye A D; Ergin, Işıl; Ocek, Zeliha

2010-11-01

Substantial regional health inequalities have been shown to exist in Turkey for major health indicators. Turkish data on hospitals deserves a closer examination with a special emphasis on the regional differences in the context of the rapid privatization of the secondary or tertiary level health services.This study aims to evaluate the change in capacity and service delivery at public and private hospitals in Turkey between 2001-2006 and to determine the regional differences. Data for this retrospective study was provided from Statistical Almanacs of Inpatient Services (2001-2006). Hospitals in each of the 81 provinces were grouped into two categories: public and private. Provinces were grouped into six regions according to a development index composed by the State Planning Organisation. The number of facilities, hospital beds, outpatient admissions, inpatient admissions (per 100 000), number of deliveries and surgical operations (per 10 000) were calculated for public and private hospitals in each province and region. Regional comparisons were based on calculation of ratios for Region 1(R1) to Region 6(R6). Public facilities had a fundamental role in service delivery. However, private sector grew rapidly in Turkey between 2001-2006 in capacity and service delivery. In public sector, there were 2.3 fold increase in the number of beds in R1 to R6 in 2001. This ratio was 69.9 fold for private sector. The substantial regional inequalities in public and private sector decreased for the private sector enormously while a little decrease was observed for the public sector. In 2001 in R1, big surgical operations were performed six times more than R6 at the public sector whereas the difference was 117.7 fold for the same operations in the same regions for the private sector. These ratios decreased to 3.6 for the public sector and 13.9 for the private sector in 2006. The private health sector has grown enormously between 2001-2006 in Turkey including the less developed regions of the country. Given the fact that majority of people living in these underdeveloped regions are uninsured, the expansion of the private sector may not contribute in reducing the inequalities in access to health care. In fact, it may widen the existing gap for access to health between high and low income earners in these underdeveloped regions.

The impact of a preloaded intraocular lens delivery system on operating room efficiency in routine cataract surgery.

PubMed

Jones, Jason J; Chu, Jeffrey; Graham, Jacob; Zaluski, Serge; Rocha, Guillermo

2016-01-01

The aim of this study was to evaluate the operational impact of using preloaded intraocular lens (IOL) delivery systems compared with manually loaded IOL delivery processes during routine cataract surgeries. Time and motion data, staff and surgery schedules, and cost accounting reports were collected across three sites located in the US, France, and Canada. Time and motion data were collected for manually loaded IOL processes and preloaded IOL delivery systems over four surgery days. Staff and surgery schedules and cost accounting reports were collected during the 2 months prior and after introduction of the preloaded IOL delivery system. The study included a total of 154 routine cataract surgeries across all three sites. Of these, 77 surgeries were performed using a preloaded IOL delivery system, and the remaining 77 surgeries were performed using a manual IOL delivery process. Across all three sites, use of the preloaded IOL delivery system significantly decreased mean total case time by 6.2%-12.0% (P<0.001 for data from Canada and the US and P<0.05 for data from France). Use of the preloaded delivery system also decreased surgeon lens time, surgeon delays, and eliminated lens touches during IOL preparation. Compared to a manual IOL delivery process, use of a preloaded IOL delivery system for cataract surgery reduced total case time, total surgeon lens time, surgeon delays, and eliminated IOL touches. The time savings provided by the preloaded IOL delivery system provide an opportunity for sites to improve routine cataract surgery throughput without impacting surgeon or staff capacity.

45 CFR 1634.9 - Selection criteria.

Code of Federal Regulations, 2014 CFR

2014-10-01

... key staff; (6) The applicant's knowledge of the various components of the legal services delivery... services to eligible clients; and (ii) its knowledge of and willingness to cooperate with other legal... applicant's capacity to ensure continuity in client services and representation of eligible clients with...

45 CFR 1634.9 - Selection criteria.

Code of Federal Regulations, 2013 CFR

2013-10-01

... key staff; (6) The applicant's knowledge of the various components of the legal services delivery... services to eligible clients; and (ii) its knowledge of and willingness to cooperate with other legal... applicant's capacity to ensure continuity in client services and representation of eligible clients with...

45 CFR 1634.9 - Selection criteria.

Code of Federal Regulations, 2012 CFR

2012-10-01

... key staff; (6) The applicant's knowledge of the various components of the legal services delivery... services to eligible clients; and (ii) its knowledge of and willingness to cooperate with other legal... applicant's capacity to ensure continuity in client services and representation of eligible clients with...

45 CFR 1634.9 - Selection criteria.

Code of Federal Regulations, 2011 CFR

2011-10-01

... key staff; (6) The applicant's knowledge of the various components of the legal services delivery... services to eligible clients; and (ii) its knowledge of and willingness to cooperate with other legal... applicant's capacity to ensure continuity in client services and representation of eligible clients with...

76 FR 9349 - Jim Woodruff Project

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-17

... month. Southeastern would compute its purchased power obligation for each delivery point monthly... rates to include a pass-through of purchased power expenses. The capacity and energy charges to preference customers can be reduced because purchased power expenses will be recovered in a separate, pass...

Climate change and temperature-dependent biogeography: oxygen limitation of thermal tolerance in animals.

PubMed

Pörtner, H O

2001-04-01

Recent years have shown a rise in mean global temperatures and a shift in the geographical distribution of ectothermic animals. For a cause and effect analysis the present paper discusses those physiological processes limiting thermal tolerance. The lower heat tolerance in metazoa compared with unicellular eukaryotes and bacteria suggests that a complex systemic rather than molecular process is limiting in metazoa. Whole-animal aerobic scope appears as the first process limited at low and high temperatures, linked to the progressively insufficient capacity of circulation and ventilation. Oxygen levels in body fluids may decrease, reflecting excessive oxygen demand at high temperatures or insufficient aerobic capacity of mitochondria at low temperatures. Aerobic scope falls at temperatures beyond the thermal optimum and vanishes at low or high critical temperatures when transition to an anaerobic mitochondrial metabolism occurs. The adjustment of mitochondrial densities on top of parallel molecular or membrane adjustments appears crucial for maintaining aerobic scope and for shifting thermal tolerance. In conclusion, the capacity of oxygen delivery matches full aerobic scope only within the thermal optimum. At temperatures outside this range, only time-limited survival is supported by residual aerobic scope, then anaerobic metabolism and finally molecular protection by heat shock proteins and antioxidative defence. In a cause and effect hierarchy, the progressive increase in oxygen limitation at extreme temperatures may even enhance oxidative and denaturation stress. As a corollary, capacity limitations at a complex level of organisation, the oxygen delivery system, define thermal tolerance limits before molecular functions become disturbed.

The Social Construction of Uncertainty in Healthcare Delivery

NASA Astrophysics Data System (ADS)

Begun, James W.; Kaissi, Amer A.

We explore the following question: How would healthcare delivery be different if uncertainty were widely recognized, accurately diagnosed, and appropriately managed? Unlike most studies of uncertainty, we examine uncertainty at more than one level of analysis, considering uncertainty that arises at the patient-clinician interaction level and at the organizational level of healthcare delivery. We consider the effects of history, as the forces and systems that currently shape and manage uncertainty have emerged over a long time period. The purpose of this broad and speculative "thought exercise" is to generate greater sensemaking of the current state of healthcare delivery, particularly in the realm of organizational and public policy, and to generate new research questions about healthcare delivery. The discussion is largely based on experience in the United States, which may limit its generalizability.

Sedimentation and the Economics of Selecting an Optimum Reservoir Size

NASA Astrophysics Data System (ADS)

Miltz, David; White, David C.

1987-08-01

This paper attempts to develop an easily reproducible methodology for the economic selection of an optimal reservoir size given an annual sedimentation rate. The optimal capacity is that at which the marginal cost of constructing additional storage capacity is equal to the dredging costs avoided by having that additional capacity available to store sediment. The cost implications of misestimating dredging costs, construction costs, and sediment delivery rates are investigated. In general, it is shown that oversizing is a rational response to uncertainty in the estimation of parameters. The sensitivity of the results to alternative discount rates is also discussed. The theoretical discussion is illustrated with a case study drawn from Highland Silver Lake in southwestern Illinois.

Adenoviral beta-adrenergic receptor kinase inhibitor gene transfer improves exercise capacity, cardiac contractility, and systemic inflammation in a model of pressure overload hypertrophy.

PubMed

Gupta, Dipin; Molina, Ezequiel J; Palma, Jon; Gaughan, John P; Long, Walter; Macha, Mahender

2008-10-01

We hypothesized that intracoronary adenoviral-mediated delivery of betaARKct would improve heart failure associated pathophysiologic abnormalities related to exercise capacity, cardiac contractility, systemic inflammation and volume overload. After aortic banding, a cohort of Sprague-Dawley rats was followed by echocardiography. When an absolute decline of 25% in fractional shortening was detected, animals were randomized to intracoronary delivery of Ad.ssARKct (n=14), Ad.beta-Gal (n=13), or followed without any other further intervention (n=18). Assessment of exercise tolerance and hemodynamic profile and measurement of markers of systemic inflammation and volume overload was performed at 7, 14, and 21 days after gene delivery. Data were analyzed using ANOVA. Animals receiving Ad.ssARKct showed improved exercise tolerance compared to Ad.Gal-treated animals at 14 days (507+/-26 s vs. 408+/-19 s, P=0.01) and 21 days (526+/-55 s vs. 323+/-19 s, P<0.001) following injection. Animals receiving Ad.ssARKct demonstrated improved +dP/dtmax (mean+/-SD, 5,581+/-960 mmHg/s vs. 3,134+/-438 mmHg/s, P<0.01) and -dP/dtmax (mean+/-SD, -3,494+/-1,269 mmHg/s vs. -1,925+/-638 mmHg/s, P<0.01) compared to Ad.Gal-treated animals at 7 days. These differences were observed up to 21 days following injection. Serum levels of IL-1, IL-6, and TNF-alpha, as well as ANP were also decreased in animals receiving Ad.betaARKct. Genetic modulation of heart failure using the betaARKct gene was associated with improved exercise capacity and cardiac function as well as amelioration in heart failure-associated profiles of systemic inflammation and volume overload.

Preterm newborns show slower repair of oxidative damage and paternal smoking associated DNA damage.

PubMed

Vande Loock, Kim; Ciardelli, Roberta; Decordier, Ilse; Plas, Gina; Haumont, Dominique; Kirsch-Volders, Micheline

2012-09-01

Newborns have to cope with hypoxia during delivery and a sudden increase in oxygen at birth. Oxygen will partly be released as reactive oxygen species having the potential to cause damage to DNA and proteins. In utero, increase of most (non)-enzymatic antioxidants occurs during last weeks of gestation, making preterm neonates probably more sensitive to oxidative stress. Moreover, it has been hypothesized that oxidative stress might be the common etiological factor for certain neonatal diseases in preterm infants. The aim of this study was to assess background DNA damage; in vitro H(2)O(2) induced oxidative DNA damage and repair capacity (residual DNA damage) in peripheral blood mononucleated cells from 25 preterm newborns and their mothers. In addition, demographic data were taken into account and repair capacity of preterm was compared with full-term newborns. Multivariate linear regression analysis revealed that preterm infants from smoking fathers have higher background DNA damage levels than those from non-smoking fathers, emphasizing the risk of paternal smoking behaviour for the progeny. Significantly higher residual DNA damage found after 15-min repair in preterm children compared to their mothers and higher residual DNA damage after 2 h compared to full-term newborns suggest a slower DNA repair capacity in preterm children. In comparison with preterm infants born by caesarean delivery, preterm infants born by vaginal delivery do repair more slowly the in vitro induced oxidative DNA damage. Final impact of passive smoking and of the slower DNA repair activity of preterm infants need to be confirmed in a larger study population combining transgenerational genetic and/or epigenetic effects, antioxidant levels, genotypes, repair enzyme efficiency/levels and infant morbidity.

Oxygen availability and skeletal muscle oxidative capacity in patients with peripheral arterial disease: Implications from in vivo and in vitro assessments.

PubMed

Hart, Corey R; Layec, Gwenael; Trinity, Joel D; Le Fur, Yann; Gifford, Jayson R; Clifton, Heather L; Richardson, Russell S

2018-06-22

Evidence suggests that peak skeletal muscle mitochondrial ATP synthesis rate (V max ) in patients with peripheral arterial disease (PAD) may be attenuated due to disease-related impairments in oxygen (O 2 ) supply. However, in vitro assessments suggest intrinsic deficits in mitochondrial respiration despite ample O 2 availability. To address this conundrum, Doppler ultrasound, near infrared spectroscopy (NIRS), phosphorus magnetic resonance spectroscopy ( 31 P-MRS), and high-resolution respirometry were combined to assess convective O 2 delivery, tissue oxygenation, V max , and skeletal muscle mitochondrial capacity (Complex I+II, State 3 respiration), respectively, in the gastrocnemius muscle of 10 patients with early-stage PAD and 11 physical activity-matched healthy controls (HC). All subjects were studied in free-flow control conditions (FF) and with reactive hyperemia (RH), induced by a period of brief ischemia during the last 30s of submaximal plantar flexion exercise. The patients with PAD repeated the FF and RH trials under hyperoxic conditions (FF+100%O 2 and RH+100%O 2 ). Compared to the HC, the patients with PAD exhibited attenuated O 2 delivery at the same absolute work rate, and attenuated tissue re-oxygenation and V max after relative intensity-matched exercise. Compared to the FF condition, only RH+100%O 2 significantly increased convective O 2 delivery (~44%), tissue re-oxygenation (~54%), and V max (~60%) in PAD (p<0.05) such that V max was now not different from the HC. Furthermore, there was no evidence of an intrinsic mitochondrial deficit in PAD, assessed in vitro with adequate O 2 . Thus, in combination, this comprehensive in vivo and in vitro investigation implicates O 2 supply as the predominant factor limiting mitochondrial oxidative capacity in early-stage PAD.

Going beyond the vertical: leveraging a national HIV quality improvement programme to address other health priorities in Haiti.

PubMed

Joseph, Jean Paul; Jerome, Gregory; Lambert, Wesler; Almazor, Patrick; Cupidon, Colette Eugene; Hirschhorn, Lisa R

2015-07-01

Although the central role of quality to achieve targeted population health goals is widely recognized, how to spread the capacity to measure and improve quality across programmes has not been widely studied. We describe the successful leveraging of expertise and framework of a national HIV quality improvement programme to spread capacity and improve quality across a network of clinics in HIV and other targeted areas of healthcare delivery in rural Haiti.The work was led by Zamni LaSante, a Haitian nongovernment organization and its sister organization, Partners In Health working in partnership with the Haitian Ministry of Health in the Plateau Central and Lower Artibonite regions in 12 public sector facilities.Data included routinely collected organizational assessments of facility quality improvement capacity, national HIV performance measures and Zamni LaSante programme records.We found that facility quality improvement capacity increased with spread from HIV to other areas of inpatient and outpatient care, including tuberculosis (TB), maternal health and inpatient services in all 12 supported healthcare facilities. A significant increase in the quality of HIV care was also seen in most areas, including CD4 monitoring, TB screening, HIV treatment (all P < 0.01) and nutritional assessment and prevention of mother-to-child transmission (both P < .05), with an increase in average facility performance from 39 to 72% (P < .01).In conclusion, using a diagonal approach to leverage a national vertical programme for wider benefit resulted in accelerated change in professional culture and increased capacity to spread quality improvement activities across facilities and areas of healthcare delivery. This led to improvement within and beyond HIV care and contributed to the goal of quality of care for all.

An intelligent healthcare management system: a new approach in work-order prioritization for medical equipment maintenance requests.

PubMed

Hamdi, Naser; Oweis, Rami; Abu Zraiq, Hamzeh; Abu Sammour, Denis

2012-04-01

The effective maintenance management of medical technology influences the quality of care delivered and the profitability of healthcare facilities. Medical equipment maintenance in Jordan lacks an objective prioritization system; consequently, the system is not sensitive to the impact of equipment downtime on patient morbidity and mortality. The current work presents a novel software system (EQUIMEDCOMP) that is designed to achieve valuable improvements in the maintenance management of medical technology. This work-order prioritization model sorts medical maintenance requests by calculating a priority index for each request. Model performance was assessed by utilizing maintenance requests from several Jordanian hospitals. The system proved highly efficient in minimizing equipment downtime based on healthcare delivery capacity, and, consequently, patient outcome. Additionally, a preventive maintenance optimization module and an equipment quality control system are incorporated. The system is, therefore, expected to improve the reliability of medical equipment and significantly improve safety and cost-efficiency.

Mapping surface charge density of lipid bilayers by quantitative surface conductivity microscopy

PubMed Central

Klausen, Lasse Hyldgaard; Fuhs, Thomas; Dong, Mingdong

2016-01-01

Local surface charge density of lipid membranes influences membrane–protein interactions leading to distinct functions in all living cells, and it is a vital parameter in understanding membrane-binding mechanisms, liposome design and drug delivery. Despite the significance, no method has so far been capable of mapping surface charge densities under physiologically relevant conditions. Here, we use a scanning nanopipette setup (scanning ion-conductance microscope) combined with a novel algorithm to investigate the surface conductivity near supported lipid bilayers, and we present a new approach, quantitative surface conductivity microscopy (QSCM), capable of mapping surface charge density with high-quantitative precision and nanoscale resolution. The method is validated through an extensive theoretical analysis of the ionic current at the nanopipette tip, and we demonstrate the capacity of QSCM by mapping the surface charge density of model cationic, anionic and zwitterionic lipids with results accurately matching theoretical values. PMID:27561322

Ultrasound: medical imaging and beyond (an invited review).

PubMed

Azhari, Haim

2012-09-01

Medical applications of ultrasound were first investigated about seventy years ago. It has rapidly evolved since then, becoming an essential tool in medical imaging. Ultrasound ability to provide real time images with frame rates exceeding several hundred frames per second allows one to view rapid anatomical changes as well as to guide minimal invasive procedures. By, combining Doppler techniques with anatomical images ultrasound provides real time quantitative flow information as well. It is portable, versatile, cost effective and considered sufficiently hazardless to monitor pregnancy. Moreover, ultrasound has the unique capacity to offer therapeutic capabilities in addition to its outstanding imaging abilities. It can be used for physiotherapy, lithotripsy, and thermal ablation, and recent studies have demonstrated its usefulness in drug delivery, gene therapy and molecular imaging. The purpose of this article is to provide an introductory review of the field covering briefly topics from basic physics through current imaging methods to therapeutic applications.

The application of Big Data in medicine: current implications and future directions.

PubMed

Austin, Christopher; Kusumoto, Fred

2016-10-01

Since the mid 1980s, the world has experienced an unprecedented explosion in the capacity to produce, store, and communicate data, primarily in digital formats. Simultaneously, access to computing technologies in the form of the personal PC, smartphone, and other handheld devices has mirrored this growth. With these enhanced capabilities of data storage and rapid computation as well as real-time delivery of information via the internet, the average daily consumption of data by an individual has grown exponentially. Unbeknownst to many, Big Data has silently crept into our daily routines and, with continued development of cheap data storage and availability of smart devices both regionally and in developing countries, the influence of Big Data will continue to grow. This influence has also carried over to healthcare. This paper will provide an overview of Big Data, its benefits, potential pitfalls, and the projected impact on the future of medicine in general and cardiology in particular.

Marijuana for Glaucoma: A Recipe for Disaster or Treatment?

PubMed Central

Sun, Xiaoshen; Xu, Chaoying S.; Chadha, Nisha; Chen, Allshine; Liu, Ji

2015-01-01

Marijuana has been shown to lower intraocular pressure (IOP) but with limited duration of action and numerous adverse effects. Use of marijuana to lower IOP as a means of glaucoma treatment would require frequent use throughout the day, leading to significant adverse effects, possible progression toward Cannabis Use Disorder (CUD), and/or withdrawal symptoms. The treatment of glaucoma based on the cannabis plant or drugs based on the cannabinoid molecule should be considered carefully before being prescribed. Considerations should include the adverse physical and psychological adverse effects, including substance abuse. Currently, the deleterious effects of marijuana outweigh the benefits of its IOP-lowering capacity in most glaucoma patients. Under extremely rare circumstances, a few categories of glaucoma patients may be potential candidates for treatment with medical marijuana. Further studies on alternate routes and more focused means of cannabinoid molecule delivery to the eye for glaucoma treatment are needed. PMID:26339209

Depression Care Management: Can Employers Purchase Improved Outcomes?

PubMed Central

Rost, Kathryn; Marshall, Donna; Shearer, Benjamin; Dietrich, Allen J.

2011-01-01

Fourteen vendors are currently selling depression care management products to US employers after randomized trials demonstrate improved work outcomes. The research team interviewed 10 (71.4%) of these vendors to compare their products to four key components of interventions demonstrated to improve work outcomes. Five of 10 depression products incorporate all four key components, three of which are sold by health maintenance organizations (HMOs); however, HMOs did not deliver these components at the recommended intensity and/or duration. Only one product delivered by a disease management company delivered all four components of care at the recommended intensity and duration. This “voltage drop,” which we anticipate will increase with product implementation, suggests that every delivery system should carefully evaluate the design of its depression product before implementation for its capacity to deliver evidence-based care, repeating these evaluations as new evidence emerges. PMID:21738872

The Anatomical and Evolutionary Relationship between Self-awareness and Theory of Mind.

PubMed

Guise, Kevin; Kelly, Karen; Romanowski, Jennifer; Vogeley, Kai; Platek, Steven M; Murray, Elizabeth; Keenan, Julian Paul

2007-06-01

Although theories that examine direct links between behavior and brain remain incomplete, it is known that brain expansion significantly correlates with caloric and oxygen demands. Therefore, one of the principles governing evolutionary cognitive neuroscience is that cognitive abilities that require significant brain function (and/or structural support) must be accompanied by significant fitness benefit to offset the increased metabolic demands. One such capacity is self-awareness (SA), which (1) is found only in the greater apes and (2) remains unclear in terms of both cortical underpinning and possible fitness benefit. In the current experiment, transcranial magnetic stimulation (TMS) was applied to the prefrontal cortex during a spatial perspective-taking task involving self and other viewpoints. It was found that delivery of TMS to the right prefrontal region disrupted self-, but not other-, perspective. These data suggest that self-awareness may have evolved in concert with other right hemisphere cognitive abilities.

Mapping surface charge density of lipid bilayers by quantitative surface conductivity microscopy

NASA Astrophysics Data System (ADS)

Klausen, Lasse Hyldgaard; Fuhs, Thomas; Dong, Mingdong

2016-08-01

Local surface charge density of lipid membranes influences membrane-protein interactions leading to distinct functions in all living cells, and it is a vital parameter in understanding membrane-binding mechanisms, liposome design and drug delivery. Despite the significance, no method has so far been capable of mapping surface charge densities under physiologically relevant conditions. Here, we use a scanning nanopipette setup (scanning ion-conductance microscope) combined with a novel algorithm to investigate the surface conductivity near supported lipid bilayers, and we present a new approach, quantitative surface conductivity microscopy (QSCM), capable of mapping surface charge density with high-quantitative precision and nanoscale resolution. The method is validated through an extensive theoretical analysis of the ionic current at the nanopipette tip, and we demonstrate the capacity of QSCM by mapping the surface charge density of model cationic, anionic and zwitterionic lipids with results accurately matching theoretical values.

Mapping surface charge density of lipid bilayers by quantitative surface conductivity microscopy.

PubMed

Klausen, Lasse Hyldgaard; Fuhs, Thomas; Dong, Mingdong

2016-08-26

Local surface charge density of lipid membranes influences membrane-protein interactions leading to distinct functions in all living cells, and it is a vital parameter in understanding membrane-binding mechanisms, liposome design and drug delivery. Despite the significance, no method has so far been capable of mapping surface charge densities under physiologically relevant conditions. Here, we use a scanning nanopipette setup (scanning ion-conductance microscope) combined with a novel algorithm to investigate the surface conductivity near supported lipid bilayers, and we present a new approach, quantitative surface conductivity microscopy (QSCM), capable of mapping surface charge density with high-quantitative precision and nanoscale resolution. The method is validated through an extensive theoretical analysis of the ionic current at the nanopipette tip, and we demonstrate the capacity of QSCM by mapping the surface charge density of model cationic, anionic and zwitterionic lipids with results accurately matching theoretical values.

Marijuana for Glaucoma: A Recipe for Disaster or Treatment?

PubMed

Sun, Xiaoshen; Xu, Chaoying S; Chadha, Nisha; Chen, Allshine; Liu, Ji

2015-09-01

Marijuana has been shown to lower intraocular pressure (IOP) but with limited duration of action and numerous adverse effects. Use of marijuana to lower IOP as a means of glaucoma treatment would require frequent use throughout the day, leading to significant adverse effects, possible progression toward Cannabis Use Disorder (CUD), and/or withdrawal symptoms. The treatment of glaucoma based on the cannabis plant or drugs based on the cannabinoid molecule should be considered carefully before being prescribed. Considerations should include the adverse physical and psychological adverse effects, including substance abuse. Currently, the deleterious effects of marijuana outweigh the benefits of its IOP-lowering capacity in most glaucoma patients. Under extremely rare circumstances, a few categories of glaucoma patients may be potential candidates for treatment with medical marijuana. Further studies on alternate routes and more focused means of cannabinoid molecule delivery to the eye for glaucoma treatment are needed.

The effects of the mode of delivery on oxidative-antioxidative balance.

PubMed

Mutlu, Birgul; Aksoy, Nurten; Cakir, Hale; Celik, Hakim; Erel, Ozcan

2011-11-01

The purpose of this study was to investigate the effects of the mode of delivery on the oxidant and antioxidant systems in mothers and infants and to demonstrate which mode leads more oxidative stress. The participants were divided into two groups according to the mode of their labour and delivery: group 1 (n = 33) women with normal labour and delivery and group 2 (n = 33) with scheduled caesarean section (C/S) and delivery. The maternal, cord, and infant blood samples in both groups were collected. The serum total antioxidant capacity (TAC) and the total oxidant status (TOS) were evaluated by using an automated colorimetric measurement method. The parameters indicating oxidative stress (TOS, oxidative stress index, and lipid hydroperoxide) in maternal, cord, and newborn blood samples were higher in patients delivering with C/S than those normal spontaneous vaginal deliveries (NSVD) patient group, while it was vice versa for TAC. It may be concluded that both the mothers and neonates in C/S group are exposed to higher oxidative stress as compared with those in NSVD group and the antioxidant mechanisms are insufficient to cope with this stress during C/S. This result indicates that the normal delivery through the physiological route is healthier for the bodies of mothers and infants.

Influence of molecular weight upon mannosylated bio-synthetic hybrids for targeted antigen presenting cell gene delivery

PubMed Central

Jones, Charles H.; Gollakota, Akhila; Chen, Mingfu; Chung, Tai-Chun; Ravikrishnan, Anitha; Zhang, Guojian; Pfeifer, Blaine A.

2015-01-01

Given the rise of antibiotic resistant microbes, genetic vaccination is a promising prophylactic strategy that enables rapid design and manufacture. Facilitating this process is the choice of vector, which is often situationally-specific and limited in engineering capacity. Furthermore, these shortcomings are usually tied to an incomplete understanding of the structure-function relationships driving vector-mediated gene delivery. Building upon our initial report of a hybrid bacterial-biomaterial gene delivery vector, a comprehensive structure-function assessment was completed using a class of mannosylated poly(beta-amino esters). Through a top-down screening methodology, an ideal polymer was selected on the basis of gene delivery efficacy and then used for the synthesis of a stratified molecular weight polymer library. By eliminating contributions of polymer chemical background, we were able to complete an in-depth assessment of gene delivery as a function of (1) polymer molecular weight, (2) relative mannose content, (3) polymer-membrane biophysical properties, (4) APC uptake specificity, and (5) serum inhibition. In summary, the flexibility and potential of the hybrid design featured in this work highlights the ability to systematically probe vector-associated properties for the development of translational gene delivery candidates. PMID:25941787

Biological Gene Delivery Vehicles: Beyond Viral Vectors

PubMed Central

Seow, Yiqi; Wood, Matthew J

2009-01-01

Gene therapy covers a broad spectrum of applications, from gene replacement and knockdown for genetic or acquired diseases such as cancer, to vaccination, each with different requirements for gene delivery. Viral vectors and synthetic liposomes have emerged as the vehicles of choice for many applications today, but both have limitations and risks, including complexity of production, limited packaging capacity, and unfavorable immunological features, which restrict gene therapy applications and hold back the potential for preventive gene therapy. While continuing to improve these vectors, it is important to investigate other options, particularly nonviral biological agents which include bacteria, bacteriophage, virus-like particles (VLPs), erythrocyte ghosts, and exosomes. Exploiting the natural properties of these biological entities for specific gene delivery applications will expand the repertoire of gene therapy vectors available for clinical use. Here, we review the prospects for nonviral biological delivery vehicles as gene therapy agents with focus on their unique evolved biological properties and respective limitations and potential applications. The potential of these nonviral biological entities to act as clinical gene therapy delivery vehicles has already been shown in clinical trials using bacteria-mediated gene transfer and with sufficient development, these entities will complement the established delivery techniques for gene therapy applications. PMID:19277019

Biological gene delivery vehicles: beyond viral vectors.

PubMed

Seow, Yiqi; Wood, Matthew J

2009-05-01

Gene therapy covers a broad spectrum of applications, from gene replacement and knockdown for genetic or acquired diseases such as cancer, to vaccination, each with different requirements for gene delivery. Viral vectors and synthetic liposomes have emerged as the vehicles of choice for many applications today, but both have limitations and risks, including complexity of production, limited packaging capacity, and unfavorable immunological features, which restrict gene therapy applications and hold back the potential for preventive gene therapy. While continuing to improve these vectors, it is important to investigate other options, particularly nonviral biological agents which include bacteria, bacteriophage, virus-like particles (VLPs), erythrocyte ghosts, and exosomes. Exploiting the natural properties of these biological entities for specific gene delivery applications will expand the repertoire of gene therapy vectors available for clinical use. Here, we review the prospects for nonviral biological delivery vehicles as gene therapy agents with focus on their unique evolved biological properties and respective limitations and potential applications. The potential of these nonviral biological entities to act as clinical gene therapy delivery vehicles has already been shown in clinical trials using bacteria-mediated gene transfer and with sufficient development, these entities will complement the established delivery techniques for gene therapy applications.

Submicron Emulsions and Their Applications in Oral Delivery.

PubMed

Mundada, Veenu; Patel, Mitali; Sawant, Krutika

2016-01-01

A "submicron emulsion" is an isotropic mixture of drug, lipids, and surfactants, usually with hydrophilic cosolvents and with droplet diameters ranging from 10 to 500 nm. Submicron emulsions are of increasing interest in medicine due to their kinetic stability, high solubilizing capacity, and tiny globule size. Because of these properties, they have been applied in various fields, such as personal care, cosmetics, health care, pharmaceuticals, and agrochemicals. Submicron emulsions are by far the most advanced nanoparticulate systems for the systemic delivery of biologically active agents for controlled drug delivery and targeting. They are designed mainly for pharmaceutical formulations suitable for various routes of administration like parenteral, ocular, transdermal, and oral. This review article describes the marked potential of submicron emulsions for oral drug delivery owing to their numerous advantages like reduced first pass metabolism, inhibition of P-glycoprotein efflux system, and enhanced absorption via intestinal lymphatic pathway. To overcome the limitations of liquid dosage forms, submicron emulsions can be formulated into solid dosage forms such as solid self-emulsifying systems. This article covers various types of submicron emulsions like microemulsion, nanoemulsion, and self-emulsifying drug delivery system (SEDDS), and their potential pharmaceutical applications in oral delivery with emphasis on their advantages, limitations, and advancements.

Encapsulation of Polymethoxyflavones in Citrus Oil Emulsion-Based Delivery Systems.

PubMed

Yang, Ying; Zhao, Chengying; Chen, Jingjing; Tian, Guifang; McClements, David Julian; Xiao, Hang; Zheng, Jinkai

2017-03-01

The purpose of this work was to elucidate the effects of citrus oil type on polymethoxyflavone (PMF) solubility and on the physicochemical properties of PMF-loaded emulsion-based delivery systems. Citrus oils were extracted from mandarin, orange, sweet orange, and bergamot. The major constituents were determined by GC/MS: sweet orange oil (97.4% d-limonene); mandarin oil (72.4% d-limonene); orange oil (67.2% d-limonene); and bergamot oil (34.6% linalyl acetate and 25.3% d-limonene). PMF-loaded emulsions were fabricated using 10% oil phase (containing 0.1% w/v nobiletin or tangeretin) and 90% aqueous phase (containing 1% w/v Tween 80) using high-pressure homogenization. Delivery systems prepared using mandarin oil had the largest mean droplet diameters (386 or 400 nm), followed by orange oil (338 or 390 nm), bergamot oil (129 or 133 nm), and sweet orange oil (122 or 126 nm) for nobiletin- or tangeretin-loaded emulsions, respectively. The optical clarity of the emulsions increased with decreasing droplet size due to reduced light scattering. The viscosities of the emulsions (with or without PMFs) were similar (1.3 to 1.4 mPa·s), despite appreciable differences in oil phase viscosity. The loading capacity and encapsulation efficiency of the emulsions depended on carrier oil type, with bergamot oil giving the highest loading capacity. In summary, differences in the composition and physical characteristics of citrus oils led to PMF-loaded emulsions with different encapsulation and physicochemical characteristics. These results will facilitate the rational design of emulsion-based delivery systems for encapsulation of PMFs and other nutraceuticals in functional foods and beverages.

Enteric trimethyl chitosan nanoparticles containing hepatitis B surface antigen for oral delivery.

PubMed

Farhadian, Asma; Dounighi, Naser Mohammadpour; Avadi, Mohammadreza

2015-01-01

Oral vaccination is the preferred route of immunization. However, the degradative condition of the gastrointestinal tract and the higher molecular size of peptides pose major challenges in developing an effective oral vaccination system. One of the most excellent methods used in the development of oral vaccine delivery system relies on the entrapment of the antigen in polymeric nanoparticles. In this work, trimethyl chitosan (TMC) nanoparticles were fabricated using ionic gelation teqnique by interaction hydroxypropyl methylcellulose phthalate (HPMCP), a pH-sensitive polymer, with TMC and the utility of the particles in the oral delivery of hepatitis B surface antigen (HBsAg) was evaluated employing solutions that simulated gastric and intestinal conditions. The particle size, morphology, zeta potential, loading capacity, loading efficiency, in vitro release behavior, structure, and morphology of nanoparticles were evaluated, and the activity of the loaded antigen was assessed. Size of the optimized TMC/HPMCP nanoparticles and that of the antigen-loaded nanoparticles were 85 nm and 158 nm, respectively. Optimum loading capacity (76.75%) and loading efficiency (86.29%) were achieved at 300 µg/mL concentration of the antigen. SEM images revealed a spherical shape as well as a smooth and near-homogenous surface of nanoparticles. Results of the in vitro release studies showed that formulation with HPMCP improved the acid stability of the TMC nanoparticles as well as their capability to preserve the loaded HBsAg from gastric destruction. The antigen showed good activity both before and after loading. The results suggest that TMC/HPMCP nanoparticles could be used in the oral delivery of HBsAg vaccine.

Nanoparticle-Enabled Transdermal Drug Delivery Systems for Enhanced Dose Control and Tissue Targeting.

PubMed

Palmer, Brian C; DeLouise, Lisa A

2016-12-15

Transdermal drug delivery systems have been around for decades, and current technologies (e.g., patches, ointments, and creams) enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases.

Nanoparticle enabled transdermal drug delivery systems for enhanced dose control and tissue targeting

PubMed Central

Palmer, Brian C.; DeLouise, Lisa A.

2017-01-01

Transdermal drug delivery systems have been around for decades, and current technologies (e.g. patches, ointments, and creams) enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases. PMID:27983701

Evaluation of Delivery Costs for External Beam Radiation Therapy and Brachytherapy for Locally Advanced Cervical Cancer Using Time-Driven Activity-Based Costing.

PubMed

Bauer-Nilsen, Kristine; Hill, Colin; Trifiletti, Daniel M; Libby, Bruce; Lash, Donna H; Lain, Melody; Christodoulou, Deborah; Hodge, Constance; Showalter, Timothy N

2018-01-01

To evaluate the delivery costs, using time-driven activity-based costing, and reimbursement for definitive radiation therapy for locally advanced cervical cancer. Process maps were created to represent each step of the radiation treatment process and included personnel, equipment, and consumable supplies used to deliver care. Personnel were interviewed to estimate time involved to deliver care. Salary data, equipment purchasing information, and facilities costs were also obtained. We defined the capacity cost rate (CCR) for each resource and then calculated the total cost of patient care according to CCR and time for each resource. Costs were compared with 2016 Medicare reimbursement and relative value units (RVUs). The total cost of radiation therapy for cervical cancer was $12,861.68, with personnel costs constituting 49.8%. Brachytherapy cost $8610.68 (66.9% of total) and consumed 423 minutes of attending radiation oncologist time (80.0% of total). External beam radiation therapy cost $4055.01 (31.5% of total). Personnel costs were higher for brachytherapy than for the sum of simulation and external beam radiation therapy delivery ($4798.73 vs $1404.72). A full radiation therapy course provides radiation oncologists 149.77 RVUs with intensity modulated radiation therapy or 135.90 RVUs with 3-dimensional conformal radiation therapy, with total reimbursement of $23,321.71 and $16,071.90, respectively. Attending time per RVU is approximately 4-fold higher for brachytherapy (5.68 minutes) than 3-dimensional conformal radiation therapy (1.63 minutes) or intensity modulated radiation therapy (1.32 minutes). Time-driven activity-based costing was used to calculate the total cost of definitive radiation therapy for cervical cancer, revealing that brachytherapy delivery and personnel resources constituted the majority of costs. However, current reimbursement policy does not reflect the increased attending physician effort and delivery costs of brachytherapy. We hypothesize that the significant discrepancy between treatment costs and physician effort versus reimbursement may be a potential driver of reported national trends toward poor compliance with brachytherapy, and we suggest re-evaluation of payment policies to incentivize quality care. Copyright © 2017 Elsevier Inc. All rights reserved.

Projections for Achieving the Lancet Commission Recommended Surgical Rate of 5000 Operations per 100,000 Population by Region-Specific Surgical Rate Estimates.

PubMed

Uribe-Leitz, Tarsicio; Esquivel, Micaela M; Molina, George; Lipsitz, Stuart R; Verguet, Stéphane; Rose, John; Bickler, Stephen W; Gawande, Atul A; Haynes, Alex B; Weiser, Thomas G

2015-09-01

We previously identified a range of 4344-5028 annual operations per 100,000 people to be related to desirable health outcomes. From this and other evidence, the Lancet Commission on Global Surgery recommends a minimum rate of 5000 operations per 100,000 people. We evaluate rates of growth and estimate the time it will take to reach this minimum surgical rate threshold. We aggregated country-level surgical rate estimates from 2004 to 2012 into the twenty-one Global Burden of Disease (GBD) regions. We calculated mean rates of surgery proportional to population size for each year and assessed the rate of growth over time. We then extrapolated the time it will take each region to reach a surgical rate of 5000 operations per 100,000 population based on linear rates of change. All but two regions experienced growth in their surgical rates during the past 8 years. Fourteen regions did not meet the recommended threshold in 2012. If surgical capacity continues to grow at current rates, seven regions will not meet the threshold by 2035. Eastern Sub-Saharan Africa will not reach the recommended threshold until 2124. The rates of growth in surgical service delivery are exceedingly variable. At current rates of surgical and population growth, 6.2 billion people (73% of the world's population) will be living in countries below the minimum recommended rate of surgical care in 2035. A strategy for strengthening surgical capacity is essential if these targets are to be met in a timely fashion as part of the integrated health system development.

In vitro digestion testing of lipid-based delivery systems: calcium ions combine with fatty acids liberated from triglyceride rich lipid solutions to form soaps and reduce the solubilization capacity of colloidal digestion products.

PubMed

Devraj, Ravi; Williams, Hywel D; Warren, Dallas B; Mullertz, Anette; Porter, Christopher J H; Pouton, Colin W

2013-01-30

In vitro digestion testing is of practical importance to predict the fate of drugs administered in lipid-based delivery systems. Calcium ions are often added to digestion media to increase the extent of digestion of long-chain triglycerides (LCTs), but the effects they have on phase behaviour of the products of digestion, and consequent drug solubilization, are not well understood. This study investigates the effect of calcium and bile salt concentrations on the rate and extent of in vitro digestion of soybean oil, as well as the solubilizing capacity of the digestion products for two poorly water-soluble drugs, fenofibrate and danazol. In the presence of higher concentrations of calcium ions, the solubilization capacities of the digests were reduced for both drugs. This effect is attributed to the formation of insoluble calcium soaps, visible as precipitates during the digestions. This reduces the availability of liberated fatty acids to form mixed micelles and vesicles, thereby reducing drug solubilization. The use of high calcium concentrations does indeed force in vitro digestion of LCTs but may overestimate the extent of drug precipitation that occurs within the intestinal lumen. Copyright © 2012 Elsevier B.V. All rights reserved.

Oil-free centrifugal hydrogen compression technology demonstration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heshmat, Hooshang

2014-05-31

One of the key elements in realizing a mature market for hydrogen vehicles is the deployment of a safe and efficient hydrogen production and delivery infrastructure on a scale that can compete economically with current fuels. The challenge, however, is that hydrogen, being the lightest and smallest of gases with a lower viscosity and density than natural gas, readily migrates through small spaces and is difficult to compresses efficiently. While efficient and cost effective compression technology is crucial to effective pipeline delivery of hydrogen, the compression methods used currently rely on oil lubricated positive displacement (PD) machines. PD compression technologymore » is very costly, has poor reliability and durability, especially for components subjected to wear (e.g., valves, rider bands and piston rings) and contaminates hydrogen with lubricating fluid. Even so called “oil-free” machines use oil lubricants that migrate into and contaminate the gas path. Due to the poor reliability of PD compressors, current hydrogen producers often install duplicate units in order to maintain on-line times of 98-99%. Such machine redundancy adds substantially to system capital costs. As such, DOE deemed that low capital cost, reliable, efficient and oil-free advanced compressor technologies are needed. MiTi’s solution is a completely oil-free, multi-stage, high-speed, centrifugal compressor designed for flow capacity of 500,000 kg/day with a discharge pressure of 1200 psig. The design employs oil-free compliant foil bearings and seals to allow for very high operating speeds, totally contamination free operation, long life and reliability. This design meets the DOE’s performance targets and achieves an extremely aggressive, specific power metric of 0.48 kW-hr/kg and provides significant improvements in reliability/durability, energy efficiency, sealing and freedom from contamination. The multi-stage compressor system concept has been validated through full scale performance testing of a single stage with helium similitude gas at full speed in accordance with ASME PTC-10. The experimental results indicated that aerodynamic performance, with respect to compressor discharge pressure, flow, power and efficiency exceeded theoretical prediction. Dynamic testing of a simulated multistage centrifugal compressor was also completed under a parallel program to validate the integrity and viability of the system concept. The results give strong confidence in the feasibility of the multi-stage design for use in hydrogen gas transportation and delivery from production locations to point of use.« less

Biodistribution of biodegradable polymeric nano-carriers loaded with busulphan and designed for multimodal imaging.

PubMed

Asem, Heba; Zhao, Ying; Ye, Fei; Barrefelt, Åsa; Abedi-Valugerdi, Manuchehr; El-Sayed, Ramy; El-Serafi, Ibrahim; Abu-Salah, Khalid M; Hamm, Jörg; Muhammed, Mamoun; Hassan, Moustapha

2016-12-19

Multifunctional nanocarriers for controlled drug delivery, imaging of disease development and follow-up of treatment efficacy are promising novel tools for disease diagnosis and treatment. In the current investigation, we present a multifunctional theranostic nanocarrier system for anticancer drug delivery and molecular imaging. Superparamagnetic iron oxide nanoparticles (SPIONs) as an MRI contrast agent and busulphan as a model for lipophilic antineoplastic drugs were encapsulated into poly (ethylene glycol)-co-poly (caprolactone) (PEG-PCL) micelles via the emulsion-evaporation method, and PEG-PCL was labelled with VivoTag 680XL fluorochrome for in vivo fluorescence imaging. Busulphan entrapment efficiency was 83% while the drug release showed a sustained pattern over 10 h. SPION loaded-PEG-PCL micelles showed contrast enhancement in T 2 *-weighted MRI with high r 2 * relaxivity. In vitro cellular uptake of PEG-PCL micelles labeled with fluorescein in J774A cells was found to be time-dependent. The maximum uptake was observed after 24 h of incubation. The biodistribution of PEG-PCL micelles functionalized with VivoTag 680XL was investigated in Balb/c mice over 48 h using in vivo fluorescence imaging. The results of real-time live imaging were then confirmed by ex vivo organ imaging and histological examination. Generally, PEG-PCL micelles were highly distributed into the lungs during the first 4 h post intravenous administration, then redistributed and accumulated in liver and spleen until 48 h post administration. No pathological impairment was found in the major organs studied. Thus, with loaded contrast agent and conjugated fluorochrome, PEG-PCL micelles as biodegradable and biocompatible nanocarriers are efficient multimodal imaging agents, offering high drug loading capacity, and sustained drug release. These might offer high treatment efficacy and real-time tracking of the drug delivery system in vivo, which is crucial for designing of an efficient drug delivery system.

Current density imaging sequence for monitoring current distribution during delivery of electric pulses in irreversible electroporation.

PubMed

Serša, Igor; Kranjc, Matej; Miklavčič, Damijan

2015-01-01

Electroporation is gaining its importance in everyday clinical practice of cancer treatment. For its success it is extremely important that coverage of the target tissue, i.e. treated tumor, with electric field is within the specified range. Therefore, an efficient tool for the electric field monitoring in the tumor during delivery of electroporation pulses is needed. The electric field can be reconstructed by the magnetic resonance electric impedance tomography method from current density distribution data. In this study, the use of current density imaging with MRI for monitoring current density distribution during delivery of irreversible electroporation pulses was demonstrated. Using a modified single-shot RARE sequence, where four 3000 V and 100 μs long pulses were included at the start, current distribution between a pair of electrodes inserted in a liver tissue sample was imaged. Two repetitions of the sequence with phases of refocusing radiofrequency pulses 90° apart were needed to acquire one current density image. For each sample in total 45 current density images were acquired to follow a standard protocol for irreversible electroporation where 90 electric pulses are delivered at 1 Hz. Acquired current density images showed that the current density in the middle of the sample increased from first to last electric pulses by 60%, i.e. from 8 kA/m2 to 13 kA/m2 and that direction of the current path did not change with repeated electric pulses significantly. The presented single-shot RARE-based current density imaging sequence was used successfully to image current distribution during delivery of short high-voltage electric pulses. The method has a potential to enable monitoring of tumor coverage by electric field during irreversible electroporation tissue ablation.

Sulfated Seaweed Polysaccharides as Multifunctional Materials in Drug Delivery Applications

PubMed Central

Cunha, Ludmylla; Grenha, Ana

2016-01-01

In the last decades, the discovery of metabolites from marine resources showing biological activity has increased significantly. Among marine resources, seaweed is a valuable source of structurally diverse bioactive compounds. The cell walls of marine algae are rich in sulfated polysaccharides, including carrageenan in red algae, ulvan in green algae and fucoidan in brown algae. Sulfated polysaccharides have been increasingly studied over the years in the pharmaceutical field, given their potential usefulness in applications such as the design of drug delivery systems. The purpose of this review is to discuss potential applications of these polymers in drug delivery systems, with a focus on carrageenan, ulvan and fucoidan. General information regarding structure, extraction process and physicochemical properties is presented, along with a brief reference to reported biological activities. For each material, specific applications under the scope of drug delivery are described, addressing in privileged manner particulate carriers, as well as hydrogels and beads. A final section approaches the application of sulfated polysaccharides in targeted drug delivery, focusing with particular interest the capacity for macrophage targeting. PMID:26927134

Capacity, pressure, demand, and flow: A conceptual framework for analyzing ecosystem service provision and delivery

USGS Publications Warehouse

Villamagna, Amy M.; Angermeier, Paul L.; Bennett, Elena M.

2013-01-01

Ecosystem services provide an instinctive way to understand the trade-offs associated with natural resource management. However, despite their apparent usefulness, several hurdles have prevented ecosystem services from becoming deeply embedded in environmental decision-making. Ecosystem service studies vary widely in focal services, geographic extent, and in methods for defining and measuring services. Dissent among scientists on basic terminology and approaches to evaluating ecosystem services create difficulties for those trying to incorporate ecosystem services into decision-making. To facilitate clearer comparison among recent studies, we provide a synthesis of common terminology and explain a rationale and framework for distinguishing among the components of ecosystem service delivery, including: an ecosystem's capacity to produce services; ecological pressures that interfere with an ecosystem's ability to provide the service; societal demand for the service; and flow of the service to people. We discuss how interpretation and measurement of these four components can differ among provisioning, regulating, and cultural services. Our flexible framework treats service capacity, ecological pressure, demand, and flow as separate but interactive entities to improve our ability to evaluate the sustainability of service provision and to help guide management decisions. We consider ecosystem service provision to be sustainable when demand is met without decreasing capacity for future provision of that service or causing undesirable declines in other services. When ecosystem service demand exceeds ecosystem capacity to provide services, society can choose to enhance natural capacity, decrease demand and/or ecological pressure, or invest in a technological substitute. Because regulating services are frequently overlooked in environmental assessments, we provide a more detailed examination of regulating services and propose a novel method for quantifying the flow of regulating services based on estimates of ecological work. We anticipate that our synthesis and framework will reduce inconsistency and facilitate coherence across analyses of ecosystem services, thereby increasing their utility in environmental decision-making.

Micromachined devices: the impact of controlled geometry from cell-targeting to bioavailability.

PubMed

Tao, Sarah L; Desai, Tejal A

2005-12-05

Advances in microelectomechanical systems (MEMS) have allowed the microfabrication of polymeric substrates and the development of a novel class of controlled delivery devices. These vehicles have specifically tailored three-dimensional physical and chemical features which, together, provide the capacity to target cells, promote unidirectional controlled release, and enhance permeation across the intestinal epithelial barrier. Examining the biological response at the microdevice biointerface may provide insight into the benefits of customized surface chemistry and structure in terms of complex drug delivery vehicle design. Therefore, the aim of this work was to determine the interfacial effects of selective surface chemistry and architecture of tomato lectin (TL)-modified poly(methyl methacrylate) (PMMA) drug delivery microdevices on the Caco-2 cell line, a model of the gastrointestinal tract.

Magnetic nanoparticles-based drug and gene delivery systems for the treatment of pulmonary diseases.

PubMed

El-Sherbiny, Ibrahim M; Elbaz, Nancy M; Sedki, Mohammed; Elgammal, Abdulaziz; Yacoub, Magdi H

2017-02-01

Magnetic nanoparticles (MNPs) have gained much attention due to their unique properties such as biocompatibility and biodegradability as well as magnetic and heat-medicated characteristics. Due to these inherent properties, MNPs have been widely used in various biomedical applications including targeted drug delivery and hyperthermia-based therapy. Hyperthermia is a promising approach for the thermal activation therapy of several diseases, including pulmonary diseases. Additionally, due to their large loading capacity and controlled release ability, several MNP-based drug delivery systems have been emerged for treatment of cystic fibrosis and lung cancer. This review provides an overview on the unique properties of MNPs and magnetic-mediated hyperthermia with emphasis on the recent biomedical applications of MNPs in treatment of both lung cancer and cystic fibrosis.

Iron oxide nanoparticles for magnetically-guided and magnetically-responsive drug delivery.

PubMed

Estelrich, Joan; Escribano, Elvira; Queralt, Josep; Busquets, Maria Antònia

2015-04-10

In this review, we discuss the recent advances in and problems with the use of magnetically-guided and magnetically-responsive nanoparticles in drug delivery and magnetofection. In magnetically-guided nanoparticles, a constant external magnetic field is used to transport magnetic nanoparticles loaded with drugs to a specific site within the body or to increase the transfection capacity. Magnetofection is the delivery of nucleic acids under the influence of a magnetic field acting on nucleic acid vectors that are associated with magnetic nanoparticles. In magnetically-responsive nanoparticles, magnetic nanoparticles are encapsulated or embedded in a larger colloidal structure that carries a drug. In this last case, an alternating magnetic field can modify the structure of the colloid, thereby providing spatial and temporal control over drug release.

Iron Oxide Nanoparticles for Magnetically-Guided and Magnetically-Responsive Drug Delivery

PubMed Central

Estelrich, Joan; Escribano, Elvira; Queralt, Josep; Busquets, Maria Antònia

2015-01-01

In this review, we discuss the recent advances in and problems with the use of magnetically-guided and magnetically-responsive nanoparticles in drug delivery and magnetofection. In magnetically-guided nanoparticles, a constant external magnetic field is used to transport magnetic nanoparticles loaded with drugs to a specific site within the body or to increase the transfection capacity. Magnetofection is the delivery of nucleic acids under the influence of a magnetic field acting on nucleic acid vectors that are associated with magnetic nanoparticles. In magnetically-responsive nanoparticles, magnetic nanoparticles are encapsulated or embedded in a larger colloidal structure that carries a drug. In this last case, an alternating magnetic field can modify the structure of the colloid, thereby providing spatial and temporal control over drug release. PMID:25867479

Enhancing Care of Aged and Dying Prisoners: Is e-Learning a Feasible Approach?

PubMed

Loeb, Susan J; Penrod, Janice; Myers, Valerie H; Baney, Brenda L; Strickfaden, Sophia M; Kitt-Lewis, Erin; Wion, Rachel K

Prisons and jails are facing sharply increased demands in caring for aged and dying inmates. Our Toolkit for Enhancing End-of-life Care in Prisons effectively addressed end-of-life (EOL) care; however, geriatric content was limited, and the product was not formatted for broad dissemination. Prior research adapted best practices in EOL care and aging; but, delivery methods lacked emerging technology-focused learning and interactivity. Our purposes were to uncover current training approaches and preferences and to ascertain the technological capacity of correctional settings to deliver computer-based and other e-learning training. An environmental scan was conducted with 11 participants from U.S. prisons and jails to ensure proper fit, in terms of content and technology capacity, between an envisioned computer-based training product and correctional settings. Environmental scan findings focused on content of training, desirable qualities of training, prominence of "homegrown" products, and feasibility of commercial e-learning. This study identified qualities of training programs to adopt and pitfalls to avoid and revealed technology-related issues to be mindful of when designing computer-based training for correctional settings, and participants spontaneously expressed an interest in geriatrics and EOL training using this learning modality as long as training allowed for tailoring of materials.

Targeted Mesoporous Silica Nanocarriers in Oncology.

PubMed

Baeza, Alejandro; Vallet-Regi, Maria

2018-02-08

Cancer is one of the major leading causes of death worldwide and its prevalence will be higher in the coming years due to the progressive aging of the population. The development of nanocarriers in oncology has provided a new hope in the fight against this terrible disease. Among the different types of nanoparticles which have been reported in the scientific literature, mesoporous silica nanoparticles (MSNs) are very promising materials due to their inherent properties such as high loading capacity of many different drugs, excellent biocompatibility and easy functionalization. This review presents the current state of the art related to the development of mesoporous silica nanocarriers for antitumoral therapy paying special attention on targeted MSN able to selectively destroy tumoral cells, reducing the side damage in healthy ones, and the basic principles of targeting tumoral tissues and cells. MSNs constitute a promising nanomaterial for drug delivery applications in antitumoral therapy as a consequence of its unique properties such as excellent biocompatibility, high loading capacity, robustness, easy production and existence of multiple strategies for their functionalization with a myriad of bio-organic moieties. In the coming years, the clever application of this material would provide novel alternatives for the treatment of this complex disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Mass Drug Administration and beyond: how can we strengthen health systems to deliver complex interventions to eliminate neglected tropical diseases?

PubMed

Macpherson, Eleanor E; Adams, Emily R; Bockarie, Moses J; Hollingsworth, T Deirdre; Kelly-Hope, Louise A; Lehane, Mike; Kovacic, Vanja; Harrison, Robert A; Paine, Mark Ji; Reimer, Lisa J; Torr, Stephen J

2015-01-01

Achieving the 2020 goals for Neglected Tropical Diseases (NTDs) requires scale-up of Mass Drug Administration (MDA) which will require long-term commitment of national and global financing partners, strengthening national capacity and, at the community level, systems to monitor and evaluate activities and impact. For some settings and diseases, MDA is not appropriate and alternative interventions are required. Operational research is necessary to identify how existing MDA networks can deliver this more complex range of interventions equitably. The final stages of the different global programmes to eliminate NTDs require eliminating foci of transmission which are likely to persist in complex and remote rural settings. Operational research is required to identify how current tools and practices might be adapted to locate and eliminate these hard-to-reach foci. Chronic disabilities caused by NTDs will persist after transmission of pathogens ceases. Development and delivery of sustainable services to reduce the NTD-related disability is an urgent public health priority. LSTM and its partners are world leaders in developing and delivering interventions to control vector-borne NTDs and malaria, particularly in hard-to-reach settings in Africa. Our experience, partnerships and research capacity allows us to serve as a hub for developing, supporting, monitoring and evaluating global programmes to eliminate NTDs.

Room-Temperature Solution Synthesis of Mesoporous Silicon for Lithium Ion Battery Anodes.

PubMed

Sun, Lin; Wang, Fei; Su, Tingting; Du, Hongbin

2017-11-22

As an important optoelectronic and energy-storage material, porous silicon (PSi) has attracted great interest in various fields. The preparation of PSi, however, usually suffers from low yields and/or complicated syntheses. Herein, we report a facile solution method to prepare PSi with controllable high specific surface area. Commercial Zintl compound Mg 2 Si readily reacts with HSiCl 3 in the presence of amines at room temperature to produce amorphous PSi in high yields, where in situ formed salt byproducts serve as templates to generate uniform mesopores of ca. 3.8 nm in diameter. After crystallization treatment at 700 °C in flow Ar gas for 40 min, the obtained crystalline PSi coated with carbon layers shows excellent electrochemical performance when served as lithium ion battery anodes. The reversible specific capacity is about 2250 mA h g -1 at 0.1 A g -1 and the capacity retention is maintained at 90% after cycling at high current density of 2 A g -1 for 320 times. This simple, facile preparation method is very promising and paves the way for massive production of porous Si as high-performance anodes in Li-ion battery industry or for other applications, such as drug delivery systems and catalysis.

Baculovirus-based genome editing in primary cells.

PubMed

Mansouri, Maysam; Ehsaei, Zahra; Taylor, Verdon; Berger, Philipp

2017-03-01

Genome editing in eukaryotes became easier in the last years with the development of nucleases that induce double strand breaks in DNA at user-defined sites. CRISPR/Cas9-based genome editing is currently one of the most powerful strategies. In the easiest case, a nuclease (e.g. Cas9) and a target defining guide RNA (gRNA) are transferred into a target cell. Non-homologous end joining (NHEJ) repair of the DNA break following Cas9 cleavage can lead to inactivation of the target gene. Specific repair or insertion of DNA with Homology Directed Repair (HDR) needs the simultaneous delivery of a repair template. Recombinant Lentivirus or Adenovirus genomes have enough capacity for a nuclease coding sequence and the gRNA but are usually too small to also carry large targeting constructs. We recently showed that a baculovirus-based multigene expression system (MultiPrime) can be used for genome editing in primary cells since it possesses the necessary capacity to carry the nuclease and gRNA expression constructs and the HDR targeting sequences. Here we present new Acceptor plasmids for MultiPrime that allow simplified cloning of baculoviruses for genome editing and we show their functionality in primary cells with limited life span and induced pluripotent stem cells (iPS). Copyright © 2017 Elsevier Inc. All rights reserved.

Periosteum mechanobiology and mechanistic insights for regenerative medicine

PubMed Central

Knothe Tate, Melissa L; Yu, Nicole Y C; Jalilian, Iman; Pereira, André F; Knothe, Ulf R

2016-01-01

Periosteum is a smart mechanobiological material that serves as a habitat and delivery vehicle for stem cells as well as biological factors that modulate tissue genesis and healing. Periosteum's remarkable regenerative capacity has been harnessed clinically for over two hundred years. Scientific studies over the past decade have begun to decipher the mechanobiology of periosteum, which has a significant role in its regenerative capacity. This integrative review outlines recent mechanobiological insights that are key to modulating and translating periosteum and its resident stem cells in a regenerative medicine context. PMID:27974968

Interdependence of the Electricity Generation System and the Natural Gas System and Implications for Energy Security

DTIC Science & Technology

2013-05-15

rates, but conservatively, two weeks to several months), firm delivery contracts (which are based on the capacity of the transmission pipelines and...gas is not guaranteed as it is not part of the capacity planning process). 0 20 40 60 80 100 120 0 2 4 6 8 10 12 D ur at io n of st or ag e su pp...military installations. For example, Tinker AFB, Robins AFB, and MCAGCC Twentynine Palms all have natural gas-fired generation or cogeneration on site

Amperometric monitoring of quercetin permeation through skin membranes.

PubMed

Rembiesa, Jadwiga; Gari, Hala; Engblom, Johan; Ruzgas, Tautgirdas

2015-12-30

Transdermal delivery of quercetin (QR, 3,3',4',5,7-pentahydroxyflavone), a natural flavonoid with a considerable antioxidant capacity, is important for medical treatment of, e.g., skin disorders. QR permeability through skin is low, which, at the same time, makes the monitoring of percutaneous QR penetration difficult. The objective of this study was to assess an electrochemical method for monitoring QR penetration through skin membranes. An electrode was covered with the membrane, exposed to QR solution, and electrode current was measured. The registered current was due to electro-oxidation of QR penetrating the membrane. Exploiting strict current-QR flux relationships diffusion coefficient, D, of QR in skin and dialysis membranes was calculated. The D values were strongly dependent on the theoretical model and parameters assumed in the processing of the amperometric data. The highest values of D were in the range of 1.6-6.1×10(-7)cm(2)/s. This was reached only for skin membranes pretreated with buffer-ethanol mixture for more than 24h. QR solutions containing penetration enhancers, ethanol and l-menthol, definitely increased D values. The results demonstrate that electrochemical setup gives a possibility to assess penetration characteristics as well as enables monitoring of penetration dynamics, which is more difficult by traditional methods using Franz cells. Copyright © 2015 Elsevier B.V. All rights reserved.

Structural design principles for delivery of bioactive components in nutraceuticals and functional foods.

PubMed

McClements, David Julian; Decker, Eric Andrew; Park, Yeonhwa; Weiss, Jochen

2009-06-01

There have been major advances in the design and fabrication of structured delivery systems for the encapsulation of nutraceutical and functional food components. A wide variety of delivery systems is now available, each with its own advantages and disadvantages for particular applications. This review begins by discussing some of the major nutraceutical and functional food components that need to be delivered and highlights the main limitations to their current utilization within the food industry. It then discusses the principles underpinning the rational design of structured delivery systems: the structural characteristics of the building blocks; the nature of the forces holding these building blocks together; and, the different ways of assembling these building blocks into structured delivery systems. Finally, we review the major types of structured delivery systems that are currently available to food scientists: lipid-based (simple, multiple, multilayer, and solid lipid particle emulsions); surfactant-based (simple micelles, mixed micelles, vesicles, and microemulsions) and biopolymer-based (soluble complexes, coacervates, hydrogel droplets, and particles). For each type of delivery system we describe its preparation, properties, advantages, and limitations.

Drug Delivery of the Future: Chasing the Invisible Gorilla

PubMed Central

Park, Kinam

2015-01-01

For more than 60 years drug delivery systems have produced numerous controlled release formulations helping patients improve compliance and maximize the drug efficacy. Development of new controlled drug delivery systems was very productive during the period 1950-1980. The productivity, as measured by the number of clinically used formulations, dropped significantly during 1980-2010. This reduced productivity needs to be understood so that the future development of drug delivery systems can be accelerated and prolific again. This requires critical evaluation of the current drug delivery field, so that the factors inhibiting rapid progress can be identified and resolved. The current drug delivery field is faced with an invisible gorilla syndrome, i.e., seeing a gorilla when it is not present and missing a gorilla when it actually exists. Overcoming this syndrome requires a new way of thinking, questioning the status quo. Advances in drug delivery technologies occur by an evolutionary process, and thus, the more trials and errors lead to faster advances. The drug delivery area needs to nurture the environment where vastly different ideas can be tested, and all data, positive or negative, need to be exchanged freely as they have equal importance. PMID:26519857

Alternative Delivery Systems: A Potential Partnership for Education and Public Broadcasting.

ERIC Educational Resources Information Center

Baltzer, Jan A.

If educators and public broadcasters are to realize their potential for providing high quality educational and cultural material to the public, they must be aware of current and upcoming technologies and work in concert to achieve their goals. Several alternative delivery systems are currently available to help educators and broadcasters expand…

Assessment of Alternative Student Aid Delivery Systems: Assessment of the Current Delivery System.

ERIC Educational Resources Information Center

Advanced Technology, Inc., Reston, VA.

The effects of the current system for delivering federal financial assistance to students under the Pell Grant, Guaranteed Student Loan (GSL), and campus-based programs are analyzed. Information is included on the use of the assessment model, which combines program evaluation, systems research, and policy analysis methodologies.…

Current Practices in the Delivery of Undergraduate Exercise Physiology Content

ERIC Educational Resources Information Center

Fisher, Michele M.

2013-01-01

The purpose of this study was to identify current practices for the delivery of exercise physiology content at the undergraduate level. An anonymous 22-item survey was sent to instructors of exercise physiology to collect information concerning the structure of course offerings and instructional practices. One hundred ten instructors responded to…

40 CFR 86.155-98 - Records required; refueling test.

Code of Federal Regulations, 2012 CFR

2012-07-01

...-integrated systems, fuel system (including fuel tank(s) capacity and location), basic engine description... odometer reading. (g) All pertinent instrument information including nozzle and fuel delivery system description. As an alternative, a reference to a vehicle test cell number may be used, with advance approval...

40 CFR 86.155-98 - Records required; refueling test.

Code of Federal Regulations, 2014 CFR

2014-07-01

...-integrated systems, fuel system (including fuel tank(s) capacity and location), basic engine description... odometer reading. (g) All pertinent instrument information including nozzle and fuel delivery system description. As an alternative, a reference to a vehicle test cell number may be used, with advance approval...

40 CFR 86.155-98 - Records required; refueling test.

Code of Federal Regulations, 2013 CFR

2013-07-01

...-integrated systems, fuel system (including fuel tank(s) capacity and location), basic engine description... odometer reading. (g) All pertinent instrument information including nozzle and fuel delivery system description. As an alternative, a reference to a vehicle test cell number may be used, with advance approval...

40 CFR 86.155-98 - Records required; refueling test.

Code of Federal Regulations, 2010 CFR

2010-07-01

...-integrated systems, fuel system (including fuel tank(s) capacity and location), basic engine description... odometer reading. (g) All pertinent instrument information including nozzle and fuel delivery system description. As an alternative, a reference to a vehicle test cell number may be used, with advance approval...

40 CFR 86.155-98 - Records required; refueling test.

Code of Federal Regulations, 2011 CFR

2011-07-01

...-integrated systems, fuel system (including fuel tank(s) capacity and location), basic engine description... odometer reading. (g) All pertinent instrument information including nozzle and fuel delivery system description. As an alternative, a reference to a vehicle test cell number may be used, with advance approval...

78 FR 37554 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-21

... that utilize cord blood as a stem cell source. Potential Commercial Applications: Drug delivery to... Stem Cells by Blocking CD47 Receptor Signaling Description of Technology: NIH researchers have... generation of self-renewing cells with a high proliferative capacity. Induced pluripotent stem cells (iPS...

Inductor-Free Wireless Energy Delivery via Maxwell's Displacement Current from an Electrodeless Triboelectric Nanogenerator.

PubMed

Cao, Xia; Zhang, Meng; Huang, Jinrong; Jiang, Tao; Zou, Jingdian; Wang, Ning; Wang, Zhong Lin

2018-02-01

Wireless power delivery has been a dream technology for applications in medical science, security, radio frequency identification (RFID), and the internet of things, and is usually based on induction coils and/or antenna. Here, a new approach is demonstrated for wireless power delivery by using the Maxwell's displacement current generated by an electrodeless triboelectric nanogenerator (TENG) that directly harvests ambient mechanical energy. A rotary electrodeless TENG is fabricated using the contact and sliding mode with a segmented structure. Due to the leakage of electric field between the segments during relative rotation, the generated Maxwell's displacement current in free space is collected by metal collectors. At a gap distance of 3 cm, the output wireless current density and voltage can reach 7 µA cm -2 and 65 V, respectively. A larger rotary electrodeless TENG and flexible wearable electrodeless TENG are demonstrated to power light-emitting diodes (LEDs) through wireless energy delivery. This innovative discovery opens a new avenue for noncontact, wireless energy transmission for applications in portable and wearable electronics. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Technology for Career Information Delivery. Conference Proceedings.

ERIC Educational Resources Information Center

Kimmel, Karen S., Ed.; Blank, Joan C., Ed.

These proceedings contain 27 papers developed for a conference at which information was provided on currently available and future technological alternatives for delivery of career information. The presentations by staff of State Occupational Information Coordinating Committees, Career Information Delivery Systems, and hardware vendors are grouped…

Energy use and life cycle greenhouse gas emissions of drones for commercial package delivery

DOE PAGES

Stolaroff, Joshuah K.; Samaras, Constantine; O'Neill, Emma R.; ...

2018-02-13

Here, the use of automated, unmanned aerial vehicles (drones) to deliver commercial packages is poised to become a new industry, significantly shifting energy use in the freight sector. Here we find the current practical range of multi-copters to be about 4 km with current battery technology, requiring a new network of urban warehouses or waystations as support. We show that, although drones consume less energy per package-km than delivery trucks, the additional warehouse energy required and the longer distances traveled by drones per package greatly increase the life-cycle impacts. Still, in most cases examined, the impacts of package delivery bymore » small drone are lower than ground-based delivery. Results suggest that, if carefully deployed, drone-based delivery could reduce greenhouse gas emissions and energy use in the freight sector. To realize the environmental benefits of drone delivery, regulators and firms should focus on minimizing extra warehousing and limiting the size of drones.« less

Gene delivery with viral vectors for cerebrovascular diseases

PubMed Central

Gan, Yu; Jing, Zheng; Stetler, R. Anne; Cao, Guodong

2017-01-01

Recent achievements in the understanding of molecular events involved in the pathogenesis of central nervous system (CNS) injury have made gene transfer a promising approach for various neurological disorders, including cerebrovascular diseases. However, special obstacles, including the post-mitotic nature of neurons and the blood-brain barrier (BBB), constitute key challenges for gene delivery to the CNS. Despite the various limitations in current gene delivery systems, a spectrum of viral vectors has been successfully used to deliver genes to the CNS. Furthermore, recent advancements in vector engineering have improved the safety and delivery of viral vectors. Numerous viral vector-based clinical trials for neurological disorders have been initiated. This review will summarize the current implementation of viral gene delivery in the context of cerebrovascular diseases including ischemic stroke, hemorrhagic stroke and subarachnoid hemorrhage (SAH). In particular, we will discuss the potentially feasible ways in which viral vectors can be manipulated and exploited for use in neural delivery and therapy. PMID:23276981

Transdermal patches: history, development and pharmacology

PubMed Central

Pastore, Michael N; Kalia, Yogeshvar N; Horstmann, Michael; Roberts, Michael S

2015-01-01

Transdermal patches are now widely used as cosmetic, topical and transdermal delivery systems. These patches represent a key outcome from the growth in skin science, technology and expertise developed through trial and error, clinical observation and evidence-based studies that date back to the first existing human records. This review begins with the earliest topical therapies and traces topical delivery to the present-day transdermal patches, describing along the way the initial trials, devices and drug delivery systems that underpin current transdermal patches and their actives. This is followed by consideration of the evolution in the various patch designs and their limitations as well as requirements for actives to be used for transdermal delivery. The properties of and issues associated with the use of currently marketed products, such as variability, safety and regulatory aspects, are then described. The review concludes by examining future prospects for transdermal patches and drug delivery systems, such as the combination of active delivery systems with patches, minimally invasive microneedle patches and cutaneous solutions, including metered-dose systems. PMID:25560046

Using grey literature to prepare pharmacy students for an evolving healthcare delivery system.

PubMed

Happe, Laura E; Walker, Desiree'

2013-05-13

To assess the impact of using "grey literature" (information internally produced in print or electronic format by agencies such as hospitals, government, businesses, etc) rather than a textbook in a course on healthcare delivery systems on students' perception of the relevance of healthcare delivery system topics and their ability to identify credible sources of this information. A reading from the grey literature was identified and assigned to the students for each topic in the course. Pre- and post-course survey instruments were used for the assessment. Students reported healthcare delivery systems topics to be moderately relevant to the profession of pharmacy on both the pre- and post-course survey instruments. Students' knowledge of current and credible sources of information on healthcare delivery system topics significantly improved based on self-reports and scores on objective assessments (p<0.05). Assignment of grey literature in a course on healthcare delivery systems can be used to ensure that information in the pharmacy school curriculum is the most current and credible information available.

Energy use and life cycle greenhouse gas emissions of drones for commercial package delivery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stolaroff, Joshuah K.; Samaras, Constantine; O'Neill, Emma R.

Here, the use of automated, unmanned aerial vehicles (drones) to deliver commercial packages is poised to become a new industry, significantly shifting energy use in the freight sector. Here we find the current practical range of multi-copters to be about 4 km with current battery technology, requiring a new network of urban warehouses or waystations as support. We show that, although drones consume less energy per package-km than delivery trucks, the additional warehouse energy required and the longer distances traveled by drones per package greatly increase the life-cycle impacts. Still, in most cases examined, the impacts of package delivery bymore » small drone are lower than ground-based delivery. Results suggest that, if carefully deployed, drone-based delivery could reduce greenhouse gas emissions and energy use in the freight sector. To realize the environmental benefits of drone delivery, regulators and firms should focus on minimizing extra warehousing and limiting the size of drones.« less

Energy use and life cycle greenhouse gas emissions of drones for commercial package delivery.

PubMed

Stolaroff, Joshuah K; Samaras, Constantine; O'Neill, Emma R; Lubers, Alia; Mitchell, Alexandra S; Ceperley, Daniel

2018-02-13

The use of automated, unmanned aerial vehicles (drones) to deliver commercial packages is poised to become a new industry, significantly shifting energy use in the freight sector. Here we find the current practical range of multi-copters to be about 4 km with current battery technology, requiring a new network of urban warehouses or waystations as support. We show that, although drones consume less energy per package-km than delivery trucks, the additional warehouse energy required and the longer distances traveled by drones per package greatly increase the life-cycle impacts. Still, in most cases examined, the impacts of package delivery by small drone are lower than ground-based delivery. Results suggest that, if carefully deployed, drone-based delivery could reduce greenhouse gas emissions and energy use in the freight sector. To realize the environmental benefits of drone delivery, regulators and firms should focus on minimizing extra warehousing and limiting the size of drones.

Critical evaluation of biodegradable polymers used in nanodrugs

PubMed Central

Marin, Edgar; Briceño, Maria Isabel; Caballero-George, Catherina

2013-01-01

Use of biodegradable polymers for biomedical applications has increased in recent decades due to their biocompatibility, biodegradability, flexibility, and minimal side effects. Applications of these materials include creation of skin, blood vessels, cartilage scaffolds, and nanosystems for drug delivery. These biodegradable polymeric nanoparticles enhance properties such as bioavailability and stability, and provide controlled release of bioactive compounds. This review evaluates the classification, synthesis, degradation mechanisms, and biological applications of the biodegradable polymers currently being studied as drug delivery carriers. In addition, the use of nanosystems to solve current drug delivery problems are reviewed. PMID:23990720

Polymeric micelles: nanocarriers for cancer-targeted drug delivery.

PubMed

Zhang, Yifei; Huang, Yixian; Li, Song

2014-08-01

Polymeric micelles represent an effective delivery system for poorly water-soluble anticancer drugs. With small size (10-100 nm) and hydrophilic shell of PEG, polymeric micelles exhibit prolonged circulation time in the blood and enhanced tumor accumulation. In this review, the importance of rational design was highlighted by summarizing the recent progress on the development of micellar formulations. Emphasis is placed on the new strategies to enhance the drug/carrier interaction for improved drug-loading capacity. In addition, the micelle-forming drug-polymer conjugates are also discussed which have both drug-loading function and antitumor activity.

Development of Drug Delivery Systems Based on Layered Hydroxides for Nanomedicine

PubMed Central

Barahuie, Farahnaz; Hussein, Mohd Zobir; Fakurazi, Sharida; Zainal, Zulkarnain

2014-01-01

Layered hydroxides (LHs) have recently fascinated researchers due to their wide application in various fields. These inorganic nanoparticles, with excellent features as nanocarriers in drug delivery systems, have the potential to play an important role in healthcare. Owing to their outstanding ion-exchange capacity, many organic pharmaceutical drugs have been intercalated into the interlayer galleries of LHs and, consequently, novel nanodrugs or smart drugs may revolutionize in the treatment of diseases. Layered hydroxides, as green nanoreservoirs with sustained drug release and cell targeting properties hold great promise of improving health and prolonging life. PMID:24802876

RNAi therapeutics for brain cancer: current advancements in RNAi delivery strategies.

PubMed

Malhotra, Meenakshi; Toulouse, André; Godinho, Bruno M D C; Mc Carthy, David John; Cryan, John F; O'Driscoll, Caitriona M

2015-10-01

Malignant primary brain tumors are aggressive cancerous cells that invade the surrounding tissues of the central nervous system. The current treatment options for malignant brain tumors are limited due to the inability to cross the blood-brain barrier. The advancements in current research has identified and characterized certain molecular markers that are essential for tumor survival, progression, metastasis and angiogenesis. These molecular markers have served as therapeutic targets for the RNAi based therapies, which enable site-specific silencing of the gene responsible for tumor proliferation. However, to bring about therapeutic success, an efficient delivery carrier that can cross the blood-brain barrier and reach the targeted site is essential. The current review focuses on the potential of targeted, non-viral and viral particles containing RNAi therapeutic molecules as delivery strategies specifically for brain tumors.

Nanoparticle Delivery Enhancement With Acoustically Activated Microbubbles

PubMed Central

Mullin, Lee B; Phillips, Linsey C; Dayton, Paul A

2013-01-01

The application of microbubbles and ultrasound to deliver nanoparticle carriers for drug and gene delivery is an area that has expanded greatly in recent years. Under ultrasound exposure, microbubbles can enhance nanoparticle delivery by increasing cellular and vascular permeability. In this review, the underlying mechanisms of enhanced nanoparticle delivery with ultrasound and microbubbles and various proposed delivery techniques are discussed. Additionally, types of nanoparticles currently being investigated in preclinical studies, as well as the general limitations and benefits of a microbubble-based approach to nanoparticle delivery are reviewed. PMID:23287914

Achieving universal health coverage in South Africa through a district health system approach: conflicting ideologies of health care provision.

PubMed

Fusheini, Adam; Eyles, John

2016-10-07

Universal Health Coverage (UHC) has emerged as a major goal for health care delivery in the post-2015 development agenda. It is viewed as a solution to health care needs in low and middle countries with growing enthusiasm at both national and global levels. Throughout the world, however, the paths of countries to UHC have differed. South Africa is currently reforming its health system with UHC through developing a national health insurance (NHI) program. This will be practically achieved through a decentralized approach, the district health system, the main vehicle for delivering services since democracy. We utilize a review of relevant documents, conducted between September 2014 and December 2015 of district health systems (DHS) and UHC and their ideological underpinnings, to explore the opportunities and challenges, of the district health system in achieving UHC in South Africa. Review of data from the NHI pilot districts suggests that as South Africa embarks on reforms toward UHC, there is a need for a minimal universal coverage and emphasis on district particularity and positive discrimination so as to bridge health inequities. The disparities across districts in relation to health profiles/demographics, health delivery performance, management of health institutions or district management capacity, income levels/socio-economic status and social determinants of health, compliance with quality standards and above all the burden of disease can only be minimised through positive discrimination by paying more attention to underserved and disadavantaged communities. We conclude that in South Africa the DHS is pivotal to health reform and UHC may be best achieved through minimal universal coverage with positive discrimination to ensure disparities across districts in relation to disease burden, human resources, financing and investment, administration and management capacity, service readiness and availability and the health access inequalities are consciously implicated. Yet ideological and practical issues make its achievement problematic.

Perceived hospital managerial competency in Tehran, Iran: is there a difference between public and private hospitals?

PubMed

Kalhor, Rohollah; Tajnesaei, Mahsa; Kakemam, Edris; Keykaleh, Mesam Safi; Kalhor, Leila

2016-12-01

Hospital managers should have enough managerial competencies to coordinate the complex environment. The underlying assumption is that there is a potential gap in management capacity between public and private hospitals in Iran. This study aims to evaluate competency level of hospital managers and to compare their competencies in public and private hospitals. This study was descriptive-analytic, carried out in 2015. A survey using a self-administered questionnaire was conducted among 127 public and private hospitals managers in Tehran Province, Iran. Respondents were asked to rate their competencies in a five-key subscale that included people-related skills, health delivery, self-management, task-related skills, and strategic planning and management. Ratings were based on a five-point Likert scale ranging from very low to excellent competency level. Self-assessment of competencies level showed that managers in all state hospitals evaluate their competency at a low level. Managers felt most competent in health-delivery skills (3.71), people-related skills (3.61), and strategic planning and management (3.57), relatively less competent in self-management (3.54) and task-related skills (3.49). While being the mean total competency levels were significantly higher among male managers, those who participated in the healthcare/hospital management training courses, and those whose primary formal qualification was management in healthcare/hospital management (P<0.05). Similarly, managers who had more experience in their current position were more likely to report higher competencies level (P<0.05). Managers in private hospitals perceived themselves to be significantly more competent than their public hospitals colleagues in most of the management facets (P<0.001). There is a perceived lack of management capacity by managers of both public and private hospitals and the gap between public and private hospitals is small. There is widespread need for management training to be made available in Iran.

Health facility service availability and readiness for intrapartum and immediate postpartum care in Malawi: A cross-sectional survey

PubMed Central

Oseni, Lolade; Mtimuni, Angella; Sethi, Reena; Rashidi, Tambudzai; Kachale, Fannie; Rawlins, Barbara; Gupta, Shivam

2017-01-01

This analysis seeks to identify strengths and gaps in the existing facility capacity for intrapartum and immediate postpartum fetal and neonatal care, using data collected as a part of Malawi’s Helping Babies Breath program evaluation. From August to September 2012, the Maternal and Child Health Integrated Program (MCHIP) conducted a cross-sectional survey in 84 Malawian health facilities to capture current health facility service availability and readiness and health worker capacity and practice pertaining to labor, delivery, and immediate postpartum care. The survey collected data on availability of equipment, supplies, and medications, and health worker knowledge and performance scores on intrapartum care simulation and actual management of real clients at a subset of facilities. We ran linear regression models to identify predictors of high simulation performance of routine delivery care and management of asphyxiated newborns across all facilities surveyed. Key supplies for infection prevention and thermal care of the newborn were found to be missing in many of the surveyed facilities. At the health center level, 75% had no clinician trained in basic emergency obstetric care or newborn care and 39% had no midwife trained in the same. We observed that there were no proportional increases in available transport and staff at a facility as catchment population increased. In simulations of management of newborns with breathing problems, health workers were able to complete a median of 10 out of 16 tasks for a full-term birth case scenario and 20 out of 30 tasks for a preterm birth case scenario. Health workers who had more years of experience appeared to perform worse. Our study provides a benchmark and highlights gaps for future evaluations and studies as Malawi continues to make strides in improving facility-based care. Further progress in reducing the burden of neonatal and fetal death in Malawi will be partly predicated on guaranteeing properly equipped and staffed facilities in addition to ensuring the presence of skilled health workers. PMID:28301484

Health facility service availability and readiness for intrapartum and immediate postpartum care in Malawi: A cross-sectional survey.

PubMed

Kozuki, Naoko; Oseni, Lolade; Mtimuni, Angella; Sethi, Reena; Rashidi, Tambudzai; Kachale, Fannie; Rawlins, Barbara; Gupta, Shivam

2017-01-01

This analysis seeks to identify strengths and gaps in the existing facility capacity for intrapartum and immediate postpartum fetal and neonatal care, using data collected as a part of Malawi's Helping Babies Breath program evaluation. From August to September 2012, the Maternal and Child Health Integrated Program (MCHIP) conducted a cross-sectional survey in 84 Malawian health facilities to capture current health facility service availability and readiness and health worker capacity and practice pertaining to labor, delivery, and immediate postpartum care. The survey collected data on availability of equipment, supplies, and medications, and health worker knowledge and performance scores on intrapartum care simulation and actual management of real clients at a subset of facilities. We ran linear regression models to identify predictors of high simulation performance of routine delivery care and management of asphyxiated newborns across all facilities surveyed. Key supplies for infection prevention and thermal care of the newborn were found to be missing in many of the surveyed facilities. At the health center level, 75% had no clinician trained in basic emergency obstetric care or newborn care and 39% had no midwife trained in the same. We observed that there were no proportional increases in available transport and staff at a facility as catchment population increased. In simulations of management of newborns with breathing problems, health workers were able to complete a median of 10 out of 16 tasks for a full-term birth case scenario and 20 out of 30 tasks for a preterm birth case scenario. Health workers who had more years of experience appeared to perform worse. Our study provides a benchmark and highlights gaps for future evaluations and studies as Malawi continues to make strides in improving facility-based care. Further progress in reducing the burden of neonatal and fetal death in Malawi will be partly predicated on guaranteeing properly equipped and staffed facilities in addition to ensuring the presence of skilled health workers.

Adjustable release of mitomycin C for inhibition of scar tissue formation after filtration surgery.

PubMed

Merritt, Sonia R; Velasquez, Gia; von Recum, Horst A

2013-11-01

The aim of this study is to demonstrate a drug delivery system with the capacity to adjust the release of mitomycin C (MMC), based on polymer composition, and inhibit fibroblast proliferation to a better effect than is currently used in glaucoma filtration surgery. The polymer used in this work is made from the oligosaccharide cyclodextrin, from which others and we have demonstrated adjustable release of small molecule drugs due to specific molecular interactions or "affinity" between drug and the cyclodextrin polymer. To adjust release rate, cyclodextrin polymers were synthesized in either dimethylformamide (DMF) or dimethyl sulfoxide, (DMSO) at a crosslinking ratio of 1:0.16 or 1:0:32 (molecule of glucose: molecule of crosslinker). The polymers were then loaded with mitomycin C, dried, and release evaluated in a physiological environment. Drug release was determined by visible spectroscopy. Released aliquots of mitomycin C were incubated with 3T3 fibroblast cells to determine cytotoxic or inhibitory effect through a cell proliferation assay. We show that by using affinity between drug and polymer, we can adjust MMC release rates to be slower and more sustained than from conventional, diffusion-only polymers, for both the DMF polymers (p = 0.00526) and the DMSO polymers (p = 0.0113). The incorporated and released MMC maintains inhibition of fibroblast proliferation much longer than is possible with a one-time application. Affinity polymers with 1:0.16 and 1:0.32 crosslink ratio showed significant inhibition of proliferation for up to 100 h (p = 0.018 and p = 0.014 respectively). The use of our controlled drug delivery technology applied after surgery could have a greater therapeutic impact than the current one-time applications of MMC. Copyright © 2013 Elsevier Ltd. All rights reserved.

Adjustable release of mitomycin C for inhibition of scar tissue formation after filtration surgery

PubMed Central

Merritt, Sonia R.; Velasquez, Gia; von Recum, Horst A.

2016-01-01

The aim of this study is to demonstrate a drug delivery system with the capacity to adjust the release of mitomycin C (MMC), based on polymer composition, and inhibit fibroblast proliferation to a better effect than is currently used in glaucoma filtration surgery. The polymer used in this work is made from the oligosaccharide cyclodextrin, from which others and we have demonstrated adjustable release of small molecule drugs due to specific molecular interactions or “affinity” between drug and the cyclodextrin polymer. To adjust release rate, cyclodextrin polymers were synthesized in either dimethylformamide (DMF) or dimethyl sulfoxide, (DMSO) at a crosslinking ratio of 1:0.16 or 1:0:32 (molecule of glucose: molecule of crosslinker). The polymers were then loaded with mitomycin C, dried, and release evaluated in a physiological environment. Drug release was determined by visible spectroscopy. Released aliquots of mitomycin C were incubated with 3T3 fibroblast cells to determine cytotoxic or inhibitory effect through a cell proliferation assay. We show that by using affinity between drug and polymer, we can adjust MMC release rates to be slower and more sustained than from conventional, diffusion-only polymers, for both the DMF polymers (p = 0.00526) and the DMSO polymers (p = 0.0113). The incorporated and released MMC maintains inhibition of fibroblast proliferation much longer than is possible with a one-time application. Affinity polymers with 1:0.16 and 1:0.32 crosslink ratio showed significant inhibition of proliferation for up to 100 h (p = 0.018 and p = 0.014 respectively). The use of our controlled drug delivery technology applied after surgery could have a greater therapeutic impact than the current one-time applications of MMC. PMID:23911951

Space Station Freedom altitude strategy

NASA Technical Reports Server (NTRS)

Mcdonald, Brian M.; Teplitz, Scott B.

1990-01-01

The Space Station Freedom (SSF) altitude strategy provides guidelines and assumptions to determine an altitude profile for Freedom. The process for determining an altitude profile incorporates several factors such as where the Space Shuttle will rendezvous with the SSF, when reboosts must occur, and what atmospheric conditions exist causing decay. The altitude strategy has an influence on all areas of SSF development and mission planning. The altitude strategy directly affects the micro-gravity environment for experiments, propulsion and control system sizing, and Space Shuttle delivery manifests. Indirectly the altitude strategy influences almost every system and operation within the Space Station Program. Evolution of the SSF altitude strategy has been a very dynamic process over the past few years. Each altitude strategy in turn has emphasized a different consideration. Examples include a constant Space Shuttle rendezvous altitude for mission planning simplicity, or constant micro-gravity levels with its inherent emphasis on payloads, or lifetime altitudes to provide a safety buffer to loss of control conditions. Currently a new altitude strategy is in development. This altitude strategy will emphasize Space Shuttle delivery optimization. Since propellant is counted against Space Shuttle payload-to-orbit capacity, lowering the rendezvous altitude will not always increase the net payload-to-orbit, since more propellant would be required for reboost. This altitude strategy will also consider altitude biases to account for Space Shuttle launch slips and an unexpected worsening of atmospheric conditions. Safety concerns will define a lower operational altitude limit, while radiation levels will define upper altitude constraints. The evolution of past and current SSF altitude strategies and the development of a new altitude strategy which focuses on operational issues as opposed to design are discussed.

Microprocessor in controlled transdermal drug delivery of anti-cancer drugs.

PubMed

Chandrashekar, N S; Shobha Rani, R H

2009-12-01

Microprocessor controlled transdermal delivery of anticancer drugs 5-Fluorouracil (5-FU) and 6-Mercaptopurine (6-MP) was developed and in vitro evaluation was done. Drugs were loaded based on the pharmacokinetics parameters. In vitro diffusion studies were carried at different current density (0.0, 0.1, 0.22, 0.50 mA/cm2). The patches were evaluated for the drug content, thickness, weight, folding endurance, flatness, thumb tack test and adhesive properties all were well with in the specification of transdermal patches with elegant and transparent in appearance. In vitro permeation studies through human cadaver skin showed, passive delivery (0.0 mA/cm2) of 6-MP was low. As the current density was progressively increased, the flux also increased. the flux also increased with 0.1 mA/cm2 for 15-20 min, but it was less than desired flux, 0.2 mA/cm2 for 30 min showed better flux than 0.1 mA/cm2 current, but lag time was more than 4 h, 0.5 mA/cm2 current for more than 1 h, flux was >159 microg/cm2 h which was desired flux for 6-MP. 5-FU flux reached the minimum effective concentration (MEC) of 54 microg/cm2 h with 0.5 mA/cm2 current for 30-45 min, drug concentration were within the therapeutic window in post-current phase. We concluded from Ohm's Law that as the resistance decreases, current increases. Skin resistance decrease with increase in time and current, increase in the drug permeation. Interestingly, for all investigated current densities, as soon as the current was switched off, 5-FU and 6-MP flux decreased fairly, but the controlled drug delivery can be achieved by switching the current for required period of time.

Formation and stabilization of nanoemulsion-based vitamin E delivery systems using natural biopolymers: Whey protein isolate and gum arabic.

PubMed

Ozturk, Bengu; Argin, Sanem; Ozilgen, Mustafa; McClements, David Julian

2015-12-01

Natural biopolymers, whey protein isolate (WPI) and gum arabic (GA), were used to fabricate emulsion-based delivery systems for vitamin E-acetate. Stable delivery systems could be formed when vitamin E-acetate was mixed with sufficient orange oil prior to high pressure homogenization. WPI (d32=0.11 μm, 1% emulsifier) was better than GA (d32=0.38 μm, 10% emulsifier) at producing small droplets at low emulsifier concentrations. However, WPI-stabilized nanoemulsions were unstable to flocculation near the protein isoelectric point (pH 5.0), at high ionic strength (>100mM), and at elevated temperatures (>60 °C), whereas GA-stabilized emulsions were stable. This difference was attributed to differences in emulsifier stabilization mechanisms: WPI by electrostatic repulsion; GA by steric repulsion. These results provide useful information about the emulsifying and stabilizing capacities of natural biopolymers for forming food-grade vitamin-enriched delivery systems. Copyright © 2015 Elsevier Ltd. All rights reserved.

Intracochlear Drug Delivery Systems

PubMed Central

Borenstein, Jeffrey T.

2011-01-01

Introduction Advances in molecular biology and in the basic understanding of the mechanisms associated with sensorineural hearing loss and other diseases of the inner ear, are paving the way towards new approaches for treatments for millions of patients. However, the cochlea is a particularly challenging target for drug therapy, and new technologies will be required to provide safe and efficacious delivery of these compounds. Emerging delivery systems based on microfluidic technologies are showing promise as a means for direct intracochlear delivery. Ultimately, these systems may serve as a means for extended delivery of regenerative compounds to restore hearing in patients suffering from a host of auditory diseases. Areas covered in this review Recent progress in the development of drug delivery systems capable of direct intracochlear delivery is reviewed, including passive systems such as osmotic pumps, active microfluidic devices, and systems combined with currently available devices such as cochlear implants. The aim of this article is to provide a concise review of intracochlear drug delivery systems currently under development, and ultimately capable of being combined with emerging therapeutic compounds for the treatment of inner ear diseases. Expert Opinion Safe and efficacious treatment of auditory diseases will require the development of microscale delivery devices, capable of extended operation and direct application to the inner ear. These advances will require miniaturization and integration of multiple functions, including drug storage, delivery, power management and sensing, ultimately enabling closed-loop control and timed-sequence delivery devices for treatment of these diseases. PMID:21615213

N(4)-[B-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan)methyl]-2'-deoxycytidine as a potential boron delivery agent with respect to glioblastoma.

PubMed

Uram, Łukasz; Nizioł, Joanna; Maj, Piotr; Sobich, Justyna; Rode, Wojciech; Ruman, Tomasz

2017-11-01

Glioblastoma multiforme (GBM) is a central nervous system tumor of grade IV, according to the WHO classification, extremely resistant to all currently used forms of therapy, including resection, radiotherapy, chemotherapy or combined therapy. Therefore, more effective treatment strategies of this tumor are needed, with boron neutron capture therapy (BNCT) being a potential solution, provided a proper cancer cells-targeted 10B delivery agent is found. In search of such an agent, toxicity and capacity to target DNA of a boronated derivative of 2'-deoxycytidine, N(4)-[B-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan)methyl]-2'-deoxycytidine (1), was tested against human tumor vs. normal cells. The present in vitro results revealed 1 to show low toxicity for human U-118 MG glioma cells (in the mM range) and even by 3-4 - fold lower against normal human fibroblasts. In accord, induction of apoptosis dependent on caspase-3 and caspase-7 was detected at high (>20mM) concentration of 1. Although demonstrated to be susceptible to phosphorylation by human deoxycytidine kinase and to undergo incorporation in cellular DNA, the boron analogue did not disturb cell proliferation when applied at non-toxic concentrations and showed low toxicity to a model metazoan organism, Caenorhabditis elegans. Thus, N(4)-[B-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan)methyl]-2'-deoxycytidine appears a promising candidate for a 10B delivery agent to be used in BNCT, with C. elegans indicated as a good model for in vivo studies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Evaluation of a Multicomponent Online Communication Professional Development Program for Early Interventionists

ERIC Educational Resources Information Center

Brown, Jennifer A.; Woods, Juliann J.

2012-01-01

Collaborative early intervention (EI) service delivery is enhanced by professional development focused on knowledge and skills in the content and process of delivering services. This article describes a multicomponent online professional development course designed to build infant toddler specialists' capacity to support children with…

Intervention Fidelity for a Complex Behaviour Change Intervention in Community Pharmacy Addressing Cardiovascular Disease Risk

ERIC Educational Resources Information Center

McNamara, K. P.; O'Reilly, S. L.; George, J.; Peterson, G. M.; Jackson, S. L.; Duncan, G.; Howarth, H.; Dunbar, J. A.

2015-01-01

Background: Delivery of cardiovascular disease (CVD) prevention programs by community pharmacists appears effective and enhances health service access. However, their capacity to implement complex behavioural change processes during patient counselling remains largely unexplored. This study aims to determine intervention fidelity by pharmacists…

Another level of leadership: nurses on boards.

PubMed

Bleich, Michael R

2014-12-01

The movement to place nurses on boards of directors is growing, enriching boards with individuals possessing knowledge of clinical quality tied to care delivery models, human resource competencies and management, finance, and organizational change. Professional development educators are poised to advance a board's capacity to address complex health care problems.

Tourism Skills Delivery: Sharing Tourism Knowledge Online

ERIC Educational Resources Information Center

Braun, Patrice; Hollick, Mary

2006-01-01

Purpose: The purpose of this paper is to share the authors' initial insights into tourism industry capacity building via flexibly delivered online skilling and knowledge sharing. Design/methodology/approach: An online research survey approach was employed, involving a sample of 64 micro tourism operators. Findings: The paper finds that the major…

Faculty Development for Continuing Interprofessional Education and Collaborative Practice

ERIC Educational Resources Information Center

Silver, Ivan L.; Leslie, Karen

2009-01-01

This article proposes a framework for faculty development in continuing interprofessional education (CIPE) and collaborative practice. The framework is built on best practices in faculty development and CIPE. It was informed by local experience in the development, delivery, and evaluation of a faculty development program to promote capacity for…

Building Leadership Capacity in the Involving Network State

ERIC Educational Resources Information Center

Pedersen, Dorthe; Tangkjaer, Christian

2013-01-01

New partnerships, cross-organisational collaborations and co-creation, digitalisation, involvement of citizens, public design and innovation stand out as new and emerging solutions in welfare delivery. However, New Public Management (NPM) seems to represent a historical repertoire of perspectives and tools that falls short of dealing with public…

Creating a Rich Learning Environment for Remote Postgraduate Learners

ERIC Educational Resources Information Center

Lonie, Anne-Louise; Andrews, Trish

2009-01-01

At Rangelands Australia, a centre in the School of Natural and Rural Systems Management at the University of Queensland, we have recently trialled virtual classroom technology for the delivery of postgraduate support courses. We wanted to explore the capacity of this learning modality to provide collaborative, interactive, synchronous learning…

48 CFR 204.7003 - Basic PII number.

Code of Federal Regulations, 2011 CFR

2011-10-01

... procurement instrument is issued or awarded. (3) Position 9. Indicate the type of instrument by entering one...) Invitations for bids—B (iii) Contracts of all types except indefinite delivery contracts, sales contracts, and...—N (xv) Do not use—O (xvi) Purchase order—automated (assign V when numbering capacity of P is...

Nanopipette delivery: influence of surface charge.

PubMed

Shi, Wenqing; Sa, Niya; Thakar, Rahul; Baker, Lane A

2015-07-21

In this report, transport through a nanopipette is studied and the interplay between current rectification and ion delivery for small pipettes is examined. First, surface charge dependence of concentration polarization effects in a quartz nanopipette was investigated. Electrical characterization was performed through current-potential (I-V) measurements. In addition, fluorescein (an anionic fluorescent probe) was utilized to optically map ion enrichment and ion depletion in the nanopipette tip. Bare nanopipettes and polyethylenimine (PEI)-modified nanopipettes were examined. Results confirm that concentration polarization is a surface charge dependent phenomenon and delivery can be controlled through modification of surface charge. The relationship between concentration polarization effects and voltage-driven delivery of charged electroactive species was investigated with a carbon ring/nanopore electrode fabricated from pyrolyzed parylene C (PPC). Factors such as surface charge polarity of the nanopipette, electrolyte pH, and electrolyte concentration were investigated. Results indicate that with modification of surface charge, additional control over delivery of charged species can be achieved.

3D printing applications for transdermal drug delivery.

PubMed

Economidou, Sophia N; Lamprou, Dimitrios A; Douroumis, Dennis

2018-06-15

The role of two and three-dimensional printing as a fabrication technology for sophisticated transdermal drug delivery systems is explored in literature. 3D printing encompasses a family of distinct technologies that employ a virtual model to produce a physical object through numerically controlled apparatuses. The applicability of several printing technologies has been researched for the direct or indirect printing of microneedle arrays or for the modification of their surface through drug-containing coatings. The findings of the respective studies are presented. The range of printable materials that are currently used or potentially can be employed for 3D printing of transdermal drug delivery (TDD) systems is also reviewed. Moreover, the expected impact and challenges of the adoption of 3D printing as a manufacturing technique for transdermal drug delivery systems, are assessed. Finally, this paper outlines the current regulatory framework associated with 3D printed transdermal drug delivery systems. Copyright © 2018 Elsevier B.V. All rights reserved.

Current Status of Messenger RNA Delivery Systems.

PubMed

Stanton, Matthew G

2018-06-01

Messenger RNA is emerging as a highly versatile biological construct for creation of impactful medicines. mRNA vaccines directed toward infectious disease and cancer are in clinical development with encouraging early reads on tolerability and efficacy. The use of mRNA to direct intense but transient expression of paracrine factors is finding utility in reprogramming progenitor cells for wound healing and cardiac regeneration and for stimulation of antitumor immune responses, at least preclinically as we await clinical results. The use of mRNA for prolonged and repeated expression of proteins and enzymes to treat rare, typically monogenic disease is nearing clinical entry. These uses of mRNA require delivery solutions, and the application of and improvement to existing nanoparticle nucleic acid delivery systems have jump started the pace of development and reenergized the field of particle based nucleic acid delivery. The current status of mRNA delivery is reviewed in this article with an eye toward clinical tractability.

Developing a Legal Framework for Advance Healthcare Planning: Comparing England & Wales and Ireland.

PubMed

Donnelly, Mary

2017-03-01

This article examines the legislative frameworks for advance healthcare planning in England & Wales (the Mental Capacity Act 2005) and in Ireland (the Assisted Decision-Making (Capacity) Act 2015), undertaking a comparative analysis of each measure, with particular focus on the detail of the approaches taken. It is only through this kind of detailed focus that the normative choices made by legislation can fully be understood and evaluated. The article argues that, in several respects, possibly because the drafters were able to reflect lessons learned from other jurisdictions, the Assisted Decision-Making (Capacity) Act 2015 provides a more rounded and complete form of advance healthcare planning than that provided by the Mental Capacity Act. This is on the basis that it provides more protection for patient choice; better potential for delivery on the choices made; and a more appropriate balance between formalities and enforceability.

Nanostructured lipid carriers to enhance transdermal delivery and efficacy of diclofenac.

PubMed

Nguyen, Chien Ngoc; Nguyen, Thi Thuy Trang; Nguyen, Hanh Thuy; Tran, Tuan Hiep

2017-10-01

Lipid carrier-mediated transdermal drug delivery offers several advantages because it is non-irritating and non-toxic, provides effective control of drug release, and forms an adhesive film that hydrates the outer skin layers. However, to penetrate the deeper skin layers, these formulations need to overcome several barriers in the stratum corneum. This study evaluates factors influencing particle size and drug-loading capacity, which play a key role in drug permeation and efficacy. Diclofenac sodium was chosen as the model drug. The fabrication of diclofenac sodium-loaded lipid nanoparticles was optimized by modulating several parameters, including the lipids and surfactants employed, the drug/lipid ratio, and the pH of the aqueous phase. The physical properties and loading efficiencies of the nanoparticles were characterized. The optimized formulation was then dispersed into a polymer solution to form a gel, which demonstrated a sustained ex vivo permeation of diclofenac sodium over 24 h through excised rat skin and a higher drug penetrating capacity than that of a commercially available gel. In vivo anti-inflammatory activity was assessed in a rat carrageenan-induced paw edema model; the anti-edema effects of the prepared gel and commercially available gel over 24 h were comparable. The present findings indicate the effects of particle size and drug loading on the ability of nanostructured lipid carrier preparations to provide transdermal drug delivery.

Targeted adenovirus mediated inhibition of NF-κB-dependent inflammatory gene expression in endothelial cells in vitro and in vivo.

PubMed

Kułdo, J M; Ásgeirsdóttir, S A; Zwiers, P J; Bellu, A R; Rots, M G; Schalk, J A C; Ogawara, K I; Trautwein, C; Banas, B; Haisma, H J; Molema, G; Kamps, J A A M

2013-02-28

In chronic inflammatory diseases the endothelium expresses mediators responsible for harmful leukocyte infiltration. We investigated whether targeted delivery of a therapeutic transgene that inhibits nuclear factor κB signal transduction could silence the proinflammatory activation status of endothelial cells. For this, an adenovirus encoding dominant-negative IκB (dnIκB) as a therapeutic transgene was employed. Selectivity for the endothelial cells was achieved by introduction of antibodies specific for inflammatory endothelial adhesion molecules E-selectin or VCAM-1 chemically linked to the virus via polyethylene glycol. In vitro, the retargeted adenoviruses selectively infected cytokine-activated endothelial cells to express functional transgene. The comparison of transductional capacity of both retargeted viruses revealed that E-selectin based transgene delivery exerted superior pharmacological effects. Targeted delivery mediated dnIκB transgene expression in endothelial cells inhibited the induced expression of several inflammatory genes, including adhesion molecules, cytokines, and chemokines. In vivo, in mice suffering from glomerulonephritis, E-selectin-retargeted adenovirus selectively homed in the kidney to microvascular glomerular endothelium. Subsequent downregulation of endothelial adhesion molecule expression 2 days after induction of inflammation demonstrated the pharmacological potential of this gene therapy approach. The data justify further studies towards therapeutic virus design and optimization of treatment schedules to investigate their capacity to interfere with inflammatory disease progression. Copyright © 2012 Elsevier B.V. All rights reserved.

Development of collagen-hydroxyapatite scaffolds incorporating PLGA and alginate microparticles for the controlled delivery of rhBMP-2 for bone tissue engineering.

PubMed

Quinlan, Elaine; López-Noriega, Adolfo; Thompson, Emmet; Kelly, Helena M; Cryan, Sally Ann; O'Brien, Fergal J

2015-01-28

The spatiotemporally controlled delivery of the pro-osteogenic factor rhBMP-2 would overcome most of the severe secondary effects linked to the products delivering this protein for bone regeneration. With this in mind, the aim of the present work was to develop a controlled rhBMP-2 release system using collagen-hydroxyapatite (CHA) scaffolds, which had been previously optimized for bone regeneration, as delivery platforms to produce a device with enhanced capacity for bone repair. Spray-drying and emulsion techniques were used to encapsulate bioactive rhBMP-2 in alginate and PLGA microparticles, with a high encapsulation efficiency. After incorporation of these microparticles into the scaffolds, rhBMP-2 was delivered in a sustained fashion for up to 28days. When tested in vitro with osteoblasts, these eluting materials showed an enhanced pro-osteogenic effect. From these results, an optimal rhBMP-2 eluting scaffold composition was selected and implanted in critical-sized calvarial defects in a rat model, where it demonstrated an excellent healing capacity in vivo. These platforms have an immense potential in the field of tissue regeneration; by tuning the specific therapeutic molecule to the tissue of interest and by utilizing different collagen-based scaffolds, similar systems can be developed for enhancing the healing of a diverse range of tissues and organs. Copyright © 2014 Elsevier B.V. All rights reserved.

Workforce capacity to address obesity: a Western Australian cross-sectional study identifies the gap between health priority and human resources needed.

PubMed

Begley, Andrea; Pollard, Christina Mary

2016-08-25

The disease burden due to poor nutrition, physical inactivity and obesity is high and increasing. An adequately sized and skilled workforce is required to respond to this issue. This study describes the public health nutrition and physical activity (NAPA) practice priorities and explores health managers and practitioner's beliefs regarding workforce capacity to deliver on these priorities. A workforce audit was conducted including a telephone survey of all managers and a postal survey of practitioners working in the area of NAPA promotion in Western Australia in 2004. Managers gave their perspective on workforce priorities, current competencies and future needs, with a 70 % response rate. Practitioners reported on public health workforce priorities, qualifications and needs, with a 56 % response rate. The top practice priorities for managers were diabetes (35 %), alcohol and other drugs (33 %), and cardiovascular disease (27 %). Obesity (19 %), poor nutrition (15 %) and inadequate physical activity (10 %) were of lower priority. For nutrition, managers identified lack of staff (60.4 %), organisational and management factors (39.5 %) and insufficient financial resources (30.2 %) as the major barriers to adequate service delivery. For physical activity services, insufficient financial resources (41.7 %) and staffing (35.4 %) and a lack of specific physical activity service specifications (25.0 %) were the main barriers. Practitioners identified inadequate staffing as the main barrier to service delivery for nutrition (42.3 %) and physical activity (23.3 %). Ideally, managers said they required 152 % more specialist nutritionists in the workforce and 131 % specialists for physical activity services to meet health outcomes in addition to other generalist staff. Human and financial resources and organisational factors were the main barriers to meeting obesity, and public health nutrition and physical activity outcomes. Services were being delivered by generalists rather than specialists, which may reduce service effectiveness. Although conclusions from this research need to take into account the fact that the audit was conducted in 2004, the findings suggest that there was a need to equip health services with an adequately skilled workforce of sufficient capacity to deliver an effective public health response to the obesity epidemic, particularly addressing poor nutrition and physical inactivity.

Method of targeted delivery of laser beam to isolated retinal rods by fiber optics.

PubMed

Sim, Nigel; Bessarab, Dmitri; Jones, C Michael; Krivitsky, Leonid

2011-11-01

A method of controllable light delivery to retinal rod cells using an optical fiber is described. Photo-induced current of the living rod cells was measured with the suction electrode technique. The approach was tested with measurements relating the spatial distribution of the light intensity to photo-induced current. In addition, the ion current responses of rod cells to polarized light at two different orientation geometries of the cells were studied.

Strengthening Community Capacity for Environmental Health Promotion through Photovoice.

PubMed

Postma, Julie; Ramon, Cristian

2016-07-01

The study aims were to: (1) Identify health promoters'; perceptions of housing issues faced by farmworker families in an agricultural community, and (2) Strengthen community capacity to promote healthy and affordable housing. Photovoice was used to identify participants'; perceptions about farmworker housing. Thematic analysis was used to analyze participant interviews. Freudenberg's "Community Capacity for Environmental Health Promotion" framework was used to organize activities that contributed to strengthening community capacity. Purposive sampling was used to recruit six bilingual health promoters into the study. A demographic questionnaire was administered to characterize participants. An interview guide was used to inquire about housing conditions and the research process. A tracking tool was used to document capacity-building activities 2 years post data collection. Housing issues faced by farmworker families included housing availability, poor conditions, and invisibility. All dimensions of community capacity were represented. Most occurred on an individual level. Health promoters identified housing issues and built community capacity to support farmworker housing. Nurses can support housing initiatives by assessing housing status, using data to support healthy housing, supporting health promoter programs in new service delivery models, and leading coalitions to address housing as a social determinant of health. © 2015 Wiley Periodicals, Inc.

Overview of States' Use of Telehealth for the Delivery of Early Intervention (IDEA Part C) Services.

PubMed

Cason, Jana; Behl, Diane; Ringwalt, Sharon

2012-01-01

Early intervention (EI) services are designed to promote the development of skills and enhance the quality of life of infants and toddlers who have been identified as having a disability or developmental delay, enhance capacity of families to care for their child with special needs, reduce future educational costs, and promote independent living (NECTAC, 2011). EI services are regulated by Part C of the Individuals with Disabilities Education Improvement Act (IDEA); however, personnel shortages, particularly in rural areas, limit access for children who qualify. Telehealth is an emerging delivery model demonstrating potential to deliver EI services effectively and efficiently, thereby improving access and ameliorating the impact of provider shortages in underserved areas. The use of a telehealth delivery model facilitates inter-disciplinary collaboration, coordinated care, and consultation with specialists not available within a local community. A survey sent by the National Early Childhood Technical Assistance Center (NECTAC) to IDEA Part C coordinators assessed their utilization of telehealth within states' IDEA Part C programs. Reimbursement for provider type and services and barriers to implement a telehealth service delivery model were identified. Representatives from 26 states and one jurisdiction responded to the NECTAC telehealth survey. Of these, 30% (n=9) indicated that they are either currently using telehealth as an adjunct service delivery model (n=6) or plan to incorporate telehealth within the next 1-2 years (n=3). Identified telehealth providers included developmental specialists, teachers of the Deaf/Hard of Hearing (DHH), speech-language pathologists, occupational therapists, physical therapists, behavior specialists, audiologists, and interpreters. Reimbursement was variable and included use of IDEA Part C funding, Medicaid, and private insurance. Expressed barriers and concerns for the implementation of telehealth as a delivery model within Part C programming included security issues (40%; n=11); privacy issues (44%; n=12); concerns about quality of services delivered via telehealth (40%; n=11); and lack of evidence to support the effectiveness of a telehealth service delivery model within IDEA Part C programming (3%; n=1). Reimbursement policy and billing processes and technology infrastructure were also identified as barriers impacting the implementation of telehealth programming. Provider shortages impact the quantity and quality of services available for children with disabilities and developmental delay, particularly in rural areas. While many states are incorporating telehealth within their Early Intervention (IDEA Part C) services in order to improve access and overcome personnel shortages, barriers persist. Policy development, education of stakeholders, research, utilization of secure and private delivery platforms, and advocacy may facilitate more widespread adoption of telehealth within IDEA Part C programs across the country.

Overview of States’ Use of Telehealth for the Delivery of Early Intervention (IDEA Part C) Services

PubMed Central

Cason, Jana; Behl, Diane; Ringwalt, Sharon

2012-01-01

Background: Early intervention (EI) services are designed to promote the development of skills and enhance the quality of life of infants and toddlers who have been identified as having a disability or developmental delay, enhance capacity of families to care for their child with special needs, reduce future educational costs, and promote independent living (NECTAC, 2011). EI services are regulated by Part C of the Individuals with Disabilities Education Improvement Act (IDEA); however, personnel shortages, particularly in rural areas, limit access for children who qualify. Telehealth is an emerging delivery model demonstrating potential to deliver EI services effectively and efficiently, thereby improving access and ameliorating the impact of provider shortages in underserved areas. The use of a telehealth delivery model facilitates inter-disciplinary collaboration, coordinated care, and consultation with specialists not available within a local community. Method: A survey sent by the National Early Childhood Technical Assistance Center (NECTAC) to IDEA Part C coordinators assessed their utilization of telehealth within states’ IDEA Part C programs. Reimbursement for provider type and services and barriers to implement a telehealth service delivery model were identified. Results: Representatives from 26 states and one jurisdiction responded to the NECTAC telehealth survey. Of these, 30% (n=9) indicated that they are either currently using telehealth as an adjunct service delivery model (n=6) or plan to incorporate telehealth within the next 1–2 years (n=3). Identified telehealth providers included developmental specialists, teachers of the Deaf/Hard of Hearing (DHH), speech-language pathologists, occupational therapists, physical therapists, behavior specialists, audiologists, and interpreters. Reimbursement was variable and included use of IDEA Part C funding, Medicaid, and private insurance. Expressed barriers and concerns for the implementation of telehealth as a delivery model within Part C programming included security issues (40%; n=11); privacy issues (44%; n=12); concerns about quality of services delivered via telehealth (40%; n=11); and lack of evidence to support the effectiveness of a telehealth service delivery model within IDEA Part C programming (3%; n=1). Reimbursement policy and billing processes and technology infrastructure were also identified as barriers impacting the implementation of telehealth programming. Conclusions: Provider shortages impact the quantity and quality of services available for children with disabilities and developmental delay, particularly in rural areas. While many states are incorporating telehealth within their Early Intervention (IDEA Part C) services in order to improve access and overcome personnel shortages, barriers persist. Policy development, education of stakeholders, research, utilization of secure and private delivery platforms, and advocacy may facilitate more widespread adoption of telehealth within IDEA Part C programs across the country. PMID:25945202

Understanding the organization of public health delivery systems: an empirical typology.

PubMed

Mays, Glen P; Scutchfield, F Douglas; Bhandari, Michelyn W; Smith, Sharla A

2010-03-01

Policy discussions about improving the U.S. health care system increasingly recognize the need to strengthen its capacities for delivering public health services. A better understanding of how public health delivery systems are organized across the United States is critical to improvement. To facilitate the development of such evidence, this article presents an empirical method of classifying and comparing public health delivery systems based on key elements of their organizational structure. This analysis uses data collected through a national longitudinal survey of local public health agencies serving communities with at least 100,000 residents. The survey measured the availability of twenty core public health activities in local communities and the types of organizations contributing to each activity. Cluster analysis differentiated local delivery systems based on the scope of activities delivered, the range of organizations contributing, and the distribution of effort within the system. Public health delivery systems varied widely in organizational structure, but the observed patterns of variation suggested that systems adhere to one of seven distinct configurations. Systems frequently migrated from one configuration to another over time, with an overall trend toward offering a broader scope of services and engaging a wider range of organizations. Public health delivery systems exhibit important structural differences that may influence their operations and outcomes. The typology developed through this analysis can facilitate comparative studies to identify which delivery system configurations perform best in which contexts.

Chronopharmaceutical Drug Delivery Systems: Hurdles, Hype or Hope?⊗

PubMed Central

Youan, Bi-Botti C.

2010-01-01

The current advances in chronobiology and the knowledge gained from chronotherapy of selected diseases strongly suggest that “the one size fits all at all times” approach to drug delivery is no longer substantiated, at least for selected bioactive agents and disease therapy or prevention. Thus, there is a critical and urgent need for chronopharmaceutical research (e.g., design and evaluation of robust, spatially and temporally controlled drug delivery systems that would be clinically intended for chronotherapy by different routes of administration). This review provides a brief overview of current delivery system intended for chronotherapy. In theory, such an ideal “magic pill” preferably with affordable cost, would improve the safety, efficacy and patient compliance of old and new drugs. However, currently, there are three major hurdles for the successful transition of such system from laboratory to patient bedside. These include the challenges to identify adequate (i) rhythmic biomaterials and systems, (ii) rhythm engineering modeling, perhaps using system biology and (iii) regulatory guidance. PMID:20438781

The change in capacity and service delivery at public and private hospitals in Turkey: A closer look at regional differences

PubMed Central

2010-01-01

Background Substantial regional health inequalities have been shown to exist in Turkey for major health indicators. Turkish data on hospitals deserves a closer examination with a special emphasis on the regional differences in the context of the rapid privatization of the secondary or tertiary level health services. This study aims to evaluate the change in capacity and service delivery at public and private hospitals in Turkey between 2001-2006 and to determine the regional differences. Methods Data for this retrospective study was provided from Statistical Almanacs of Inpatient Services (2001-2006). Hospitals in each of the 81 provinces were grouped into two categories: public and private. Provinces were grouped into six regions according to a development index composed by the State Planning Organisation. The number of facilities, hospital beds, outpatient admissions, inpatient admissions (per 100 000), number of deliveries and surgical operations (per 10 000) were calculated for public and private hospitals in each province and region. Regional comparisons were based on calculation of ratios for Region 1(R1) to Region 6(R6). Results Public facilities had a fundamental role in service delivery. However, private sector grew rapidly in Turkey between 2001-2006 in capacity and service delivery. In public sector, there were 2.3 fold increase in the number of beds in R1 to R6 in 2001. This ratio was 69.9 fold for private sector. The substantial regional inequalities in public and private sector decreased for the private sector enormously while a little decrease was observed for the public sector. In 2001 in R1, big surgical operations were performed six times more than R6 at the public sector whereas the difference was 117.7 fold for the same operations in the same regions for the private sector. These ratios decreased to 3.6 for the public sector and 13.9 for the private sector in 2006. Conclusions The private health sector has grown enormously between 2001-2006 in Turkey including the less developed regions of the country. Given the fact that majority of people living in these underdeveloped regions are uninsured, the expansion of the private sector may not contribute in reducing the inequalities in access to health care. In fact, it may widen the existing gap for access to health between high and low income earners in these underdeveloped regions. PMID:21040539

Incorporation of photosenzitizer hypericin into synthetic lipid-based nano-particles for drug delivery and large unilamellar vesicles with different content of cholesterol

NASA Astrophysics Data System (ADS)

Joniova, Jaroslava; Blascakova, Ludmila; Jancura, Daniel; Nadova, Zuzana; Sureau, Franck; Miskovsky, Pavol

2014-08-01

Low-density lipoproteins (LDL) and high-density lipoproteins (HDL) are attractive natural occurring vehicles for drug delivery and targeting to cancer tissues. The capacity of both types of the lipoproteins to bind hydrophobic drugs and their functionality as drug carriers have been examined in several studies and it has been also shown that mixing of anticancer drugs with LDL or HDL before administration led to an increase of cytotoxic effects of the drugs in the comparison when the drugs were administered alone. However, a difficult isolation of the lipoproteins in large quantity from a biological organism as well as a variability of the composition and size of these molecules makes practical application of LDL and HDL as drug delivery systems quite complicated. Synthetic LDL and HDL and large unilamellar vesicles (LUV) are potentially suitable candidates to substitute the native lipoproteins for targeted and effective drug delivery. In this work, we have studied process of an association of potent photosensitizer hypericin (Hyp) with synthetic lipid-based nano-particles (sLNP) and large unilamellar vesicles (LUV) containing various amount of cholesterol. Cholesterol is one of the main components of both LDL and HDL particles and its presence in biological membranes is known to be a determining factor for membrane properties. It was found that the behavior of Hyp incorporation into sLNP particles with diameter ca ~ 90 nm is qualitatively very similar to that of Hyp incorporation into LDL (diameter ca. 22 nm) and these particles are able to enter U-87 MG cells by endocytosis. The presence of cholesterol in LUV influences the capacity of these vesicles to incorporate Hyp into their structure.

Characterization of polyethylene glycol-grafted polyethylenimine and superparamagnetic iron oxide nanoparticles (PEG-g-PEI-SPION) as an MRI-visible vector for siRNA delivery in gastric cancer in vitro and in vivo.

PubMed

Chen, Yinting; Lian, Guoda; Liao, Chengde; Wang, Weiwei; Zeng, Linjuan; Qian, Chenchen; Huang, Kaihong; Shuai, Xintao

2013-07-01

Gene therapy is a promising therapeutic method but is severely hampered due to its lack of an ideal delivery system. Therefore, in this study, a nonviral and magnetic resonance imaging (MRI) visible vector, polyethylene glycol-grafted polyethylenimine and superparamagnetic iron oxide nanoparticles (PEG-g-PEI-SPION) was used as a nanocarrier for small interfering RNA (siRNA) delivery in gastric cancer. Biophysical characterization of PEG-g-PEI-SPION was systematically analyzed, including size, zeta potential, siRNA condensation capacity, cell viability, transfection efficiency, cellular uptake, and MRI-visible function in vivo. Besides, CD44 variant isoform 6 (CD44v6), a protein marker for metastatic behavior in gastric cancer, and was chose as the target gene to further analyze the siRNA delivery function of PEG-g-PEI-SPION. Under comprehensive analysis, the appropriate N/P ratio of PEG-g-PEI-SPION/siRNA was 10, and siRNA targeting at human CD44v6 (siCD44v6) transferred by PEG-g-PEI-SPION was effective at downregulating the CD44v6 expression of gastric carcinoma cell line SGC-7901 in vitro. Moreover, knockdown of CD44v6 impaired migrating and invasive abilities of SGC-7901 cells. Furthermore, PEG-g-PEI-SPION was a highly efficient contrast agent for MRI scan in vivo. PEG-g-PEI-SPION was a promising nonviral vector with molecular image tracing capacity for cancer gene therapy. And CD44v6 was a potential target gene for the prevention and detection of metastatic behavior in gastric cancer.

Targeted myocardial delivery of GDF11 gene rejuvenates the aged mouse heart and enhances myocardial regeneration after ischemia-reperfusion injury.

PubMed

Du, Guo-Qing; Shao, Zheng-Bo; Wu, Jie; Yin, Wen-Juan; Li, Shu-Hong; Wu, Jun; Weisel, Richard D; Tian, Jia-Wei; Li, Ren-Ke

2017-01-01

Ischemic cardiac injury is the main contributor to heart failure, and the regenerative capacity of intrinsic stem cells plays an important role in tissue repair after injury. However, stem cells in aged individuals have reduced regenerative potential and aged tissues lack the capacity to renew. Growth differentiation factor 11 (GDF11), from the activin-transforming growth factor β superfamily, has been shown to promote stem cell activity and rejuvenation. We carried out non-invasive targeted delivery of the GDF11 gene to the heart using ultrasound-targeted microbubble destruction (UTMD) and cationic microbubble (CMB) to investigate the ability of GDF11 to rejuvenate the aged heart and improve tissue regeneration after injury. Young (3 months) and old (21 months) mice were used to evaluate the expression of GDF11 mRNA in the myocardium at baseline and after ischemia/reperfusion (I/R) and myocardial infarction. GDF11 expression decreased with age and following myocardial injury. UTMD-mediated delivery of the GDF11 plasmid to the aged heart after I/R injury effectively and selectively increased GDF11 expression in the heart, and improved cardiac function and reduced infarct size. Over-expression of GDF11 decreased senescence markers, p16 and p53, as well as the number of p16 + cells in old mouse hearts. Furthermore, increased proliferation of cardiac stem cell antigen 1 (Sca-1 + ) cells and increased homing of endothelial progenitor cells and angiogenesis in old ischemic hearts occurred after GDF11 over-expression. Repetitive targeted delivery of the GDF11 gene via UTMD can rejuvenate the aged mouse heart and protect it from I/R injury.

Regional Delivery of Chimeric Antigen Receptor-Engineered T Cells Effectively Targets HER2+ Breast Cancer Metastasis to the Brain.

PubMed

Priceman, Saul J; Tilakawardane, Dileshni; Jeang, Brook; Aguilar, Brenda; Murad, John P; Park, Anthony K; Chang, Wen-Chung; Ostberg, Julie R; Neman, Josh; Jandial, Rahul; Portnow, Jana; Forman, Stephen J; Brown, Christine E

2018-01-01

Purpose: Metastasis to the brain from breast cancer remains a significant clinical challenge, and may be targeted with CAR-based immunotherapy. CAR design optimization for solid tumors is crucial due to the absence of truly restricted antigen expression and potential safety concerns with "on-target off-tumor" activity. Here, we have optimized HER2-CAR T cells for the treatment of breast to brain metastases, and determined optimal second-generation CAR design and route of administration for xenograft mouse models of breast metastatic brain tumors, including multifocal and leptomeningeal disease. Experimental Design: HER2-CAR constructs containing either CD28 or 4-1BB intracellular costimulatory signaling domains were compared for functional activity in vitro by measuring cytokine production, T-cell proliferation, and tumor killing capacity. We also evaluated HER2-CAR T cells delivered by intravenous, local intratumoral, or regional intraventricular routes of administration using in vivo human xenograft models of breast cancer that have metastasized to the brain. Results: Here, we have shown that HER2-CARs containing the 4-1BB costimulatory domain confer improved tumor targeting with reduced T-cell exhaustion phenotype and enhanced proliferative capacity compared with HER2-CARs containing the CD28 costimulatory domain. Local intracranial delivery of HER2-CARs showed potent in vivo antitumor activity in orthotopic xenograft models. Importantly, we demonstrated robust antitumor efficacy following regional intraventricular delivery of HER2-CAR T cells for the treatment of multifocal brain metastases and leptomeningeal disease. Conclusions: Our study shows the importance of CAR design in defining an optimized CAR T cell, and highlights intraventricular delivery of HER2-CAR T cells for treating multifocal brain metastases. Clin Cancer Res; 24(1); 95-105. ©2017 AACR . ©2017 American Association for Cancer Research.

In vivo evaluation of a cancer therapy strategy combining HSV1716-mediated oncolysis with gene transfer and targeted radiotherapy.

PubMed

Sorensen, Annette; Mairs, Robert J; Braidwood, Lynne; Joyce, Craig; Conner, Joe; Pimlott, Sally; Brown, Moira; Boyd, Marie

2012-04-01

Oncolytic herpes viruses show promise for cancer treatment. However, it is unlikely that they will fulfill their therapeutic potential when used as monotherapies. An alternative strategy is to use these viruses not only as oncolytic agents but also as a delivery mechanism of therapeutic transgenes to enhance tumor cell killing. The herpes simplex virus 1 deletion mutant HSV1716 is a conditionally replicating oncolytic virus that selectively replicates in and lyses dividing tumor cells. It has a proven safety profile in clinical trials and has demonstrated efficacy as a gene-delivery vehicle. To enhance its therapeutic potential, we have engineered HSV1716 to convey the noradrenaline transporter (NAT) gene (HSV1716/NAT), whose expression endows infected cells with the capacity to accumulate the noradrenaline analog metaiodobenzylguanidine (MIBG). Thus, the NAT gene-infected cells are susceptible to targeted radiotherapy using radiolabeled (131)I-MIBG, a strategy that has already shown promise for combined targeted radiotherapy-gene therapy in cancer cells after plasmid-mediated transfection. We used HSV1716/NAT as a dual cell lysis-gene delivery vehicle for targeting the NAT transgene to human tumor xenografts in vivo. In tumor xenografts that did not express NAT, intratumoral or intravenous injection of HSV1716/NAT induced the capacity for active uptake of (131)I-MIBG. Administration of HSV1716/NAT and (131)I-MIBG resulted in decreased tumor growth and enhanced survival relative to injection of either agent alone. Efficacy was dependent on the scheduling of delivery of the 2 agents. These findings support a role for combination radiotherapy-gene therapy for cancer using HSV1716 expressing the NAT transgene and targeted radionuclide therapy.

Using Quality Improvement Methods and Time-Driven Activity-Based Costing to Improve Value-Based Cancer Care Delivery at a Cancer Genetics Clinic.

PubMed

Tan, Ryan Y C; Met-Domestici, Marie; Zhou, Ke; Guzman, Alexis B; Lim, Soon Thye; Soo, Khee Chee; Feeley, Thomas W; Ngeow, Joanne

2016-03-01

To meet increasing demand for cancer genetic testing and improve value-based cancer care delivery, National Cancer Centre Singapore restructured the Cancer Genetics Service in 2014. Care delivery processes were redesigned. We sought to improve access by increasing the clinic capacity of the Cancer Genetics Service by 100% within 1 year without increasing direct personnel costs. Process mapping and plan-do-study-act (PDSA) cycles were used in a quality improvement project for the Cancer Genetics Service clinic. The impact of interventions was evaluated by tracking the weekly number of patient consultations and access times for appointments between April 2014 and May 2015. The cost impact of implemented process changes was calculated using the time-driven activity-based costing method. Our study completed two PDSA cycles. An important outcome was achieved after the first cycle: The inclusion of a genetic counselor increased clinic capacity by 350%. The number of patients seen per week increased from two in April 2014 (range, zero to four patients) to seven in November 2014 (range, four to 10 patients). Our second PDSA cycle showed that manual preappointment reminder calls reduced the variation in the nonattendance rate and contributed to a further increase in patients seen per week to 10 in May 2015 (range, seven to 13 patients). There was a concomitant decrease in costs of the patient care cycle by 18% after both PDSA cycles. This study shows how quality improvement methods can be combined with time-driven activity-based costing to increase value. In this paper, we demonstrate how we improved access while reducing costs of care delivery. Copyright © 2016 by American Society of Clinical Oncology.

Synthesis and characterization of cloisite-30B clay dispersed poly (acryl amide/sodium alginate)/AgNp hydrogel composites for the study of BSA protein drug delivery and antibacterial activity

NASA Astrophysics Data System (ADS)

Nanjunda Reddy, B. H.; Ranjan Rauta, Pradipta; Venkatalakshimi, V.; Sreenivasa, Swamy

2018-02-01

The aim of this research is to inspect the effect of Cloisite-30B (C30B) modified clay dispersed poly (acrylamide-co-Sodiumalginate)/AgNp hydrogel nanocomposites (PASA/C30B/Ag) for drug delivery and antibacterial activity. A novel hydrogel composite based sodium alginate (SA) and the inorganic modified clay with silver nano particle (C30B/AgNps)polymer hydrogel composites are synthesized via the graft copolymerization of acrylamide (AAm) in an aqueous medium with methylene bisacrylamide (MBA) as a crosslinking agent and ammonium per sulfate(APS) as an initiator. The UV/Visible spectroscopy of obtained composites is successfully studied, which confirms the occurrence of AgNps in the hydrogel composites. And the swelling capacity and bovine serum albumin (BSA) protein as model drug delivery study for these hydrogel nanocomposites have been carried out. The C30B/Ag filled hydrogel composites exhibit superior water absorbency or swelling capacity compared to pure samples and it is establish that the formulations with clay (C30B) dispersed silver nanocomposite hydrogels show improved and somewhat faster rate of drug delivery than other formulations(pure systems) and SEM and TEM reports suggests that the size of AgNps in the composite hydrogels is in the range of 5-10 nm with shrunken surface and the antibacterial characterizations for gram positive and gram negative bacteria are carried out by using Streptococcus faecalis (S. Faecalis) and Escherichia coli (E.coli) as model bacteria and the hydrogel composites of PASA/C30B/Ag shows exceptional antibacterial activity against both the bacteria as compared to pure hydrogel composites samples.

Preparation and in vitro antimicrobial activity of silver-bearing degradable polymeric nanoparticles of polyphosphoester-block-poly(L-lactide).

PubMed

Lim, Young H; Tiemann, Kristin M; Heo, Gyu Seong; Wagers, Patrick O; Rezenom, Yohannes H; Zhang, Shiyi; Zhang, Fuwu; Youngs, Wiley J; Hunstad, David A; Wooley, Karen L

2015-02-24

The development of well-defined polymeric nanoparticles (NPs) as delivery carriers for antimicrobials targeting human infectious diseases requires rational design of the polymer template, an efficient synthetic approach, and fundamental understanding of the developed NPs, e.g., drug loading/release, particle stability, and other characteristics. Herein, we developed and evaluated the in vitro antimicrobial activity of silver-bearing, fully biodegradable and functional polymeric NPs. A series of degradable polymeric nanoparticles (dNPs), composed of phosphoester and L-lactide and designed specifically for silver loading into the hydrophilic shell and/or the hydrophobic core, were prepared as potential delivery carriers for three different types of silver-based antimicrobials-silver acetate or one of two silver carbene complexes (SCCs). Silver-loading capacities of the dNPs were not influenced by the hydrophilic block chain length, loading site (i.e., core or shell), or type of silver compound, but optimization of the silver feed ratio was crucial to maximize the silver loading capacity of dNPs, up to ca. 12% (w/w). The release kinetics of silver-bearing dNPs revealed 50% release at ca. 2.5-5.5 h depending on the type of silver compound. In addition, we undertook a comprehensive evaluation of the rates of hydrolytic or enzymatic degradability and performed structural characterization of the degradation products. Interestingly, packaging of the SCCs in the dNP-based delivery system improved minimum inhibitory concentrations up to 70%, compared with the SCCs alone, as measured in vitro against 10 contemporary epidemic strains of Staphylococcus aureus and eight uropathogenic strains of Escherichia coli. We conclude that these dNP-based delivery systems may be beneficial for direct epithelial treatment and/or prevention of ubiquitous bacterial infections, including those of the skin and urinary tract.

Estimation of capacities on Florida freeways.

DOT National Transportation Integrated Search

2014-09-01

Current capacity estimates within Floridas travel time reliability tools rely on the Highway Capacity Manual (HCM 2010) to : estimate capacity under various conditions. Field measurements show that the capacities of Florida freeways are noticeably...

Exploring the role of peptides in polymer-based gene delivery.

PubMed

Sun, Yanping; Yang, Zhen; Wang, Chunxi; Yang, Tianzhi; Cai, Cuifang; Zhao, Xiaoyun; Yang, Li; Ding, Pingtian

2017-09-15

Polymers are widely studied as non-viral gene vectors because of their strong DNA binding ability, capacity to carry large payload, flexibility of chemical modifications, low immunogenicity, and facile processes for manufacturing. However, high cytotoxicity and low transfection efficiency substantially restrict their application in clinical trials. Incorporating functional peptides is a promising approach to address these issues. Peptides demonstrate various functions in polymer-based gene delivery systems, such as targeting to specific cells, breaching membrane barriers, facilitating DNA condensation and release, and lowering cytotoxicity. In this review, we systematically summarize the role of peptides in polymer-based gene delivery, and elaborate how to rationally design polymer-peptide based gene delivery vectors. Polymers are widely studied as non-viral gene vectors, but suffer from high cytotoxicity and low transfection efficiency. Incorporating short, bioactive peptides into polymer-based gene delivery systems can address this issue. Peptides demonstrate various functions in polymer-based gene delivery systems, such as targeting to specific cells, breaching membrane barriers, facilitating DNA condensation and release, and lowering cytotoxicity. In this review, we highlight the peptides' roles in polymer-based gene delivery, and elaborate how to utilize various functional peptides to enhance the transfection efficiency of polymers. The optimized peptide-polymer vectors should be able to alter their structures and functions according to biological microenvironments and utilize inherent intracellular pathways of cells, and consequently overcome the barriers during gene delivery to enhance transfection efficiency. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Unified heuristics to solve routing problem of reverse logistics in sustainable supply chain

NASA Astrophysics Data System (ADS)

Anbuudayasankar, S. P.; Ganesh, K.; Lenny Koh, S. C.; Mohandas, K.

2010-03-01

A reverse logistics problem, motivated by many real-life applications, is examined where bottles/cans in which products are delivered from a processing depot to customers in one period are available for return to the depot in the following period. The picked-up bottles/cans need to be adjusted in the place of delivery load. This problem is termed as simultaneous delivery and pick-up problem with constrained capacity (SDPC). We develop three unified heuristics based on extended branch and bound heuristic, genetic algorithm and simulated annealing to solve SDPC. These heuristics are also designed to solve standard travelling salesman problem (TSP) and TSP with simultaneous delivery and pick-up (TSDP). We tested the heuristics on standard, derived and randomly generated datasets of TSP, TSDP and SDPC and obtained satisfying results with high convergence in reasonable time.

A therapeutic nanoparticle vaccine against Trypanosoma cruzi in a BALB/c mouse model of Chagas disease

PubMed Central

Barry, Meagan A.; Wang, Qian; Jones, Kathryn M.; Heffernan, Michael J.; Buhaya, Munir H.; Beaumier, Coreen M.; Keegan, Brian P.; Zhan, Bin; Dumonteil, Eric; Bottazzi, Maria Elena; Hotez, Peter J.

2016-01-01

ABSTRACT Chagas disease, caused by Trypanosoma cruzi, results in an acute febrile illness that progresses to chronic chagasic cardiomyopathy in 30% of patients. Current treatments have significant side effects and poor efficacy during the chronic phase; therefore, there is an urgent need for new treatment modalities. A robust TH1-mediated immune response correlates with favorable clinical outcomes. A therapeutic vaccine administered to infected individuals could bolster the immune response, thereby slowing or stopping the progression of chagasic cardiomyopathy. Prior work in mice has identified an efficacious T. cruzi DNA vaccine encoding Tc24. To elicit a similar protective cell-mediated immune response to a Tc24 recombinant protein, we utilized a poly(lactic-co-glycolic acid) nanoparticle delivery system in conjunction with CpG motif-containing oligodeoxynucleotides as an immunomodulatory adjuvant. In a BALB/c mouse model, the vaccine produced a TH1-biased immune response, as demonstrated by a significant increase in antigen-specific IFNγ-producing splenocytes, IgG2a titers, and proliferative capacity of CD8+ T cells. When tested for therapeutic efficacy, significantly reduced systemic parasitemia was seen during peak parasitemia. Additionally, there was a significant reduction in cardiac parasite burden and inflammatory cell infiltrate. This is the first study demonstrating immunogenicity and efficacy of a therapeutic Chagas vaccine using a nanoparticle delivery system. PMID:26890466

How is Primary Health Care conceptualised in nursing in Australia? A review of the literature.

PubMed

Henderson, Julie; Koehne, Kristy; Verrall, Claire; Gebbie, Kristine; Fuller, Jeffrey

2014-07-01

Australia, in common with many other countries, is expanding the role of Primary Health Care (PHC) to manage the growing burden of chronic disease and prevent hospitalisation. Australia's First National Primary Health Care Strategy released in 2010 places general practice at the centre of care delivery, reflecting a constitutional division of labour in which the Commonwealth government's primary means of affecting care delivery in this sector is through rebates for services delivered from the universal healthcare system Medicare. A review of Australian nursing literature was undertaken for 2006-2011. This review explores three issues in relation to these changes: How PHC is conceptualised within Australian nursing literature; who is viewed as providing PHC; and barriers and enablers to the provision of comprehensive PHC. A review of the literature suggests that the terms 'PHC' and 'primary care' are used interchangeably and that PHC is now commonly associated with services provided by practice nurses. Four structural factors are identified for a shift away from comprehensive PHC, namely fiscal barriers, educational preparation for primary care practice, poor role definition and interprofessional relationships. The paper concludes that while moves towards increasing capacity in general practice have enhanced nursing roles, current policy and the nature of private business funding alongside some medical opposition limit opportunities for Australian nurses working in general practice. © 2013 John Wiley & Sons Ltd.

A Comprehensive Framework for International Medical Programs: A 2017 consensus statement from the American College of Academic International Medicine

PubMed Central

Garg, Manish; Peck, Gregory L.; Arquilla, Bonnie; Miller, Andrew C.; Soghoian, Sari E.; Anderson III, Harry L.; Bloem, Christina; Firstenberg, Michael S.; Galwankar, Sagar C.; Guo, Weidun Alan; Izurieta, Ricardo; Krebs, Elizabeth; Hansoti, Bhakti; Nanda, Sudip; Nwachuku, Chinenye O.; Nwomeh, Benedict; Paladino, Lorenzo; Papadimos, Thomas J.; Sharpe, Richard P.; Swaroop, Mamta; Stawicki, Stanislaw P.

2017-01-01

The American College of Academic International Medicine (ACAIM) represents a group of clinicians who seek to promote clinical, educational, and scientific collaboration in the area of Academic International Medicine (AIM) to address health care disparities and improve patient care and outcomes globally. Significant health care delivery and quality gaps persist between high-income countries (HICs) and low-and-middle-income countries (LMICs). International Medical Programs (IMPs) are an important mechanism for addressing these inequalities. IMPs are international partnerships that primarily use education and training-based interventions to build sustainable clinical capacity. Within this overall context, a comprehensive framework for IMPs (CFIMPs) is needed to assist HICs and LMICs navigate the development of IMPs. The aim of this consensus statement is to highlight best practices and engage the global community in ACAIM's mission. Through this work, we highlight key aspects of IMPs including: (1) the structure; (2) core principles for successful and ethical development; (3) information technology; (4) medical education and training; (5) research and scientific investigation; and (6) program durability. The ultimate goal of current initiatives is to create a foundation upon which ACAIM and other organizations can begin to formalize a truly global network of clinical education/training and care delivery sites, with long-term sustainability as the primary pillar of international inter-institutional collaborations. PMID:29291171

Influence of molecular weight upon mannosylated bio-synthetic hybrids for targeted antigen presenting cell gene delivery.

PubMed

Jones, Charles H; Gollakota, Akhila; Chen, Mingfu; Chung, Tai-Chun; Ravikrishnan, Anitha; Zhang, Guojian; Pfeifer, Blaine A

2015-07-01

Given the rise of antibiotic resistant microbes, genetic vaccination is a promising prophylactic strategy that enables rapid design and manufacture. Facilitating this process is the choice of vector, which is often situationally-specific and limited in engineering capacity. Furthermore, these shortcomings are usually tied to an incomplete understanding of the structure-function relationships driving vector-mediated gene delivery. Building upon our initial report of a hybrid bacterial-biomaterial gene delivery vector, a comprehensive structure-function assessment was completed using a class of mannosylated poly(beta-amino esters). Through a top-down screening methodology, an ideal polymer was selected on the basis of gene delivery efficacy and then used for the synthesis of a stratified molecular weight polymer library. By eliminating contributions of polymer chemical background, we were able to complete an in-depth assessment of gene delivery as a function of (1) polymer molecular weight, (2) relative mannose content, (3) polymer-membrane biophysical properties, (4) APC uptake specificity, and (5) serum inhibition. In summary, the flexibility and potential of the hybrid design featured in this work highlights the ability to systematically probe vector-associated properties for the development of translational gene delivery candidates. Copyright © 2015 Elsevier Ltd. All rights reserved.

Relationship between regional population and healthcare delivery in Japan.

PubMed

Niga, Takeo; Mori, Maiko; Kawahara, Kazuo

2016-01-01

In order to address regional inequality in healthcare delivery in Japan, healthcare districts were established in 1985. However, regional healthcare delivery has now become a national issue because of population migration and the aging population. In this study, the state of healthcare delivery at the district level is examined by analyzing population, the number of physicians, and the number of hospital beds. The results indicate a continuing disparity in healthcare delivery among districts. We find that the rate of change in population has a strong positive correlation with that in the number of physicians and a weak positive correlation with that in the number of hospital beds. In addition, principal component analysis is performed on three variables: the rate of change in population, the number of physicians per capita, and the number of hospital beds per capita. This analysis suggests that the two principal components contribute 90.1% of the information. The first principal component is thought to show the effect of the regulations on hospital beds. The second principal component is thought to show the capacity to recruit physicians. This study indicates that an adjustment to the regulations on hospital beds as well as physician allocation by public funds may be key to resolving the impending issue of regionally disproportionate healthcare delivery.

Maternal c-reactive protein and oxidative stress markers as predictors of delivery latency in patients experiencing preterm premature rupture of membranes.

PubMed

Ryu, Hyun Kyung; Moon, Jong Ho; Heo, Hyun Ji; Kim, Jong Woon; Kim, Yoon Ha

2017-02-01

To evaluate the usefulness of maternal serum c-reactive protein (CRP), lipid peroxide, and oxygen radical absorbance capacity (ORAC), to predict the interval between membrane rupture and delivery in patients with preterm premature rupture of membranes (PPROM). The present prospective study included patients with singleton pregnancies experiencing PPROM at earlier than 34 weeks of pregnancy who underwent spontaneous vaginal delivery between August 1, 2010 and July 31, 2013 at Chonnam National University Hospital, Republic of Korea. Patients were categorized based on whether delivery occurred within 3 days of PPROM or after. CRP levels, lipid peroxide (using malondialdehyde levels), ORAC, protein carbonyl, and other potential risk factors were compared between the groups. There were 72 patients included. Maternal serum CRP levels, malondialdehyde levels, and Bishop Score were higher in patients who underwent delivery within 3 days (all P<0.05); ORAC levels were lower among these patients (P=0.002). A receiver operating characteristic curve analysis showed that CRP, malondialdehyde, and ORAC levels were predictive of delivery within 3 days after PPROM. Maternal serum CRP, malondialdehyde, and ORAC levels at admission were useful in predicting the latent period in patients with PPROM. © 2016 International Federation of Gynecology and Obstetrics.

Asymptotically reliable transport of multimedia/graphics over wireless channels

NASA Astrophysics Data System (ADS)

Han, Richard Y.; Messerschmitt, David G.

1996-03-01

We propose a multiple-delivery transport service tailored for graphics and video transported over connections with wireless access. This service operates at the interface between the transport and application layers, balancing the subjective delay and image quality objectives of the application with the low reliability and limited bandwidth of the wireless link. While techniques like forward-error correction, interleaving and retransmission improve reliability over wireless links, they also increase latency substantially when bandwidth is limited. Certain forms of interactive multimedia datatypes can benefit from an initial delivery of a corrupt packet to lower the perceptual latency, as long as reliable delivery occurs eventually. Multiple delivery of successively refined versions of the received packet, terminating when a sufficiently reliable version arrives, exploits the redundancy inherently required to improve reliability without a traffic penalty. Modifications to acknowledgment-repeat-request (ARQ) methods to implement this transport service are proposed, which we term `leaky ARQ'. For the specific case of pixel-coded window-based text/graphics, we describe additional functions needed to more effectively support urgent delivery and asymptotic reliability. X server emulation suggests that users will accept a multi-second delay between a (possibly corrupt) packet and the ultimate reliably-delivered version. The relaxed delay for reliable delivery can be exploited for traffic capacity improvement using scheduling of retransmissions.

A simulation-optimization model for water-resources management, Santa Barbara, California

USGS Publications Warehouse

Nishikawa, Tracy

1998-01-01

In times of drought, the local water supplies of the city of Santa Barbara, California, are insufficient to satisfy water demand. In response, the city has built a seawater desalination plant and gained access to imported water in 1997. Of primary concern to the city is delivering water from the various sources at a minimum cost while satisfying water demand and controlling seawater intrusion that might result from the overpumping of ground water. A simulation-optimization model has been developed for the optimal management of Santa Barbara?s water resources. The objective is to minimize the cost of water supply while satisfying various physical and institutional constraints such as meeting water demand, maintaining minimum hydraulic heads at selected sites, and not exceeding water-delivery or pumping capacities. The model is formulated as a linear programming problem with monthly management periods and a total planning horizon of 5 years. The decision variables are water deliveries from surface water (Gibraltar Reservoir, Cachuma Reservoir, Cachuma Reservoir cumulative annual carryover, Mission Tunnel, State Water Project, and desalinated seawater) and ground water (13 production wells). The state variables are hydraulic heads. Basic assumptions for all simulations are that (1) the cost of water varies with source but is fixed over time, and (2) only existing or planned city wells are considered; that is, the construction of new wells is not allowed. The drought of 1947?51 is Santa Barbara?s worst drought on record, and simulated surface-water supplies for this period were used as a basis for testing optimal management of current water resources under drought conditions. Assumptions that were made for this base case include a head constraint equal to sea level at the coastal nodes; Cachuma Reservoir carryover of 3,000 acre-feet per year, with a maximum carryover of 8,277 acre-feet; a maximum annual demand of 15,000 acre-feet; and average monthly capacities for the Cachuma and the Gibraltar Reservoirs. The base-case results indicate that water demands can be met, with little water required from the most expensive water source (desalinated seawater), at a total cost of $5.56 million over the 5-year planning horizon. The simulation model has drains, which operate as nonlinear functions of heads and could affect the model solutions. However, numerical tests show that the drains have little effect on the optimal solution. Sensitivity analyses on the base case yield the following results: If allowable Cachuma Reservoir carryover is decreased by about 50 percent, then costs increase by about 14 percent; if the peak demand is decreased by 7 percent, then costs will decrease by about 14 percent; if the head constraints are loosened to -30 feet, then the costs decrease by about 18 percent; if the heads are constrained such that a zero hydraulic gradient condition occurs at the ocean boundary, then the optimization problem does not have a solution; if the capacity of the desalination plant is constrained to zero acre-feet, then the cost increases by about 2 percent; and if the carryover of State Water Project water is implemented, then the cost decreases by about 0.5 percent. Four additional monthly diversion distribution scenarios for the reservoirs were tested: average monthly Cachuma Reservoir deliveries with the actual (scenario 1) and proposed (scenario 2) monthly distributions of Gibraltar Reservoir water, and variable monthly Cachuma Reservoir deliveries with the actual (scenario 3) and proposed (scenario 4) monthly distributions of Gibraltar Reservoir water. Scenario 1 resulted in a total cost of about $7.55 million, scenario 2 resulted in a total cost of about $5.07 million, and scenarios 3 and 4 resulted in a total cost of about $4.53 million. Sensitivities of the scenarios 1 and 2 to desalination-plant capacity and State Water Project water carryover were tested. The scenario 1 sensitivity analysis indicated that incorpo

Challenges for the surgical capacity building of township hospitals among the Central China: a retrospective study.

PubMed

Li, Zhong; Yang, Jian; Wu, Yue; Pan, Zijin; He, Xiaoqun; Li, Boyang; Zhang, Liang

2018-05-02

China's rapid transition in healthcare service system has posed considerable challenges for the primary care system. Little is known regarding the capacity of township hospitals (THs) to deliver surgical care in rural China with over 600 million lives. We aimed to ascertain its current performance, barriers, and summary lessons for its re-building in central China. This study was conducted in four counties from two provinces in central China. The New Rural Cooperative Medical System (NRCMS) claim data from two counties in Hubei province was analyzed to describe the current situation of surgical care provision. Based on previous studies, self-administered questionnaire was established to collect key indicators from 60 THs from 2011 to 2015, and social and economic statuses of the sampling townships were collected from the local statistical yearbook. Semi-structured interviews were conducted among seven key administrators in the THs that did not provide appendectomy care in 2015. Determinants of appendectomy care provision were examined using a negative binominal regression model. First, with the rapid increase in inpatient services provided by the THs, their proportion of surgical service provision has been nibbled by out-of-county facilities. Second, although DY achieved a stable performance, the total amount of appendectomy provided by the 60 THs decreased to 589 in 2015 from 1389 in 2011. Moreover, their proportion reduced to 26.77% in 2015 from 41.84% in 2012. Third, an increasing number of THs did not provide appendectomy in 2015, with the shortage of anesthesiologists and equipment as the most mentioned reasons (46.43%). Estimation results from the negative binomial model indicated that the annual average per capita disposable income and tightly integrated delivery networks (IDNs) negatively affected the amount of appendectomy provided by THs. By contrast, the probability of appendectomy provision by THs was increased by performance-related payment (PRP). Out-of-pocket (OOP) cost gap of appendectomy services between the two different levels of facilities, payment method, and the size of THs presented no observable improvement to the likelihood of appendectomy care in THs. The county-level health system did not effectively respond to the continuously increasing surgical care need. The surgical capacity of THs declined with the surgical patterns' simplistic and quantity reduction. Deficits and critical challenges for surgical capacity building in central China were identified, including shortage of human resources and medical equipment and increasing income. Moreover, tight IDNs do not temporarily achieve capacity building. Therefore, the reimbursement rate should be further ranged, and physicians should be incentivized appropriately. The administrators, policy makers, and medical staff of THs should be aware of these findings owing to the potential benefits for the capacity building of the rural healthcare system.

Links among Social Status, Service Delivery Mode, and Service Delivery Preference in LD, Low-Achieving, and Normally Achieving Elementary-Aged Children.

ERIC Educational Resources Information Center

Le Mare, Lucy; de la Ronde, Marie

2000-01-01

Relations among social status, current service delivery, and service delivery preferences were examined in 42 students with learning disabilities (LD), 40 low-achieving, and 42 average/high-achieving students in grades 2-4 and 6-7. Most students preferred pullout service to in-class service. Only among LD students were self- and peer-rated social…

Localized delivery of growth factors for periodontal tissue regeneration: role, strategies, and perspectives.

PubMed

Chen, Fa-Ming; Shelton, Richard M; Jin, Yan; Chapple, Iain L C

2009-05-01

Difficulties associated with achieving predictable periodontal regeneration, means that novel techniques need to be developed in order to regenerate the extensive soft and hard tissue destruction that results from periodontitis. Localized delivery of growth factors to the periodontium is an emerging and versatile therapeutic approach, with the potential to become a powerful tool in future regenerative periodontal therapy. Optimized delivery regimes and well-defined release kinetics appear to be logical prerequisites for safe and efficacious clinical application of growth factors and to avoid unwanted side effects and toxicity. While adequate concentrations of growth factor(s) need to be appropriately localized, delivery vehicles are also expected to possess properties such as protein protection, precision in controlled release, biocompatibility and biodegradability, self-regulated therapeutic activity, potential for multiple delivery, and good cell/tissue penetration. Here, current knowledge, recent advances, and future possibilities of growth factor delivery strategies are outlined for periodontal regeneration. First, the role of those growth factors that have been implicated in the periodontal healing/regeneration process, general requirements for their delivery, and the different material types available are described. A detailed discussion follows of current strategies for the selection of devices for localized growth factor delivery, with particular emphasis placed upon their advantages and disadvantages and future prospects for ongoing studies in reconstructing the tooth supporting apparatus.

Engineering β-sheet peptide assemblies for biomedical applications.

PubMed

Yu, Zhiqiang; Cai, Zheng; Chen, Qiling; Liu, Menghua; Ye, Ling; Ren, Jiaoyan; Liao, Wenzhen; Liu, Shuwen

2016-03-01

Hydrogels have been widely studied in various biomedical applications, such as tissue engineering, cell culture, immunotherapy and vaccines, and drug delivery. Peptide-based nanofibers represent a promising new strategy for current drug delivery approaches and cell carriers for tissue engineering. This review focuses on the recent advances in the use of self-assembling engineered β-sheet peptide assemblies for biomedical applications. The applications of peptide nanofibers in biomedical fields, such as drug delivery, tissue engineering, immunotherapy, and vaccines, are highlighted. The current challenges and future perspectives for self-assembling peptide nanofibers in biomedical applications are discussed.

Nanocomposite thin films for triggerable drug delivery.

PubMed

Vannozzi, Lorenzo; Iacovacci, Veronica; Menciassi, Arianna; Ricotti, Leonardo

2018-05-01

Traditional drug release systems normally rely on a passive delivery of therapeutic compounds, which can be partially programmed, prior to injection or implantation, through variations in the material composition. With this strategy, the drug release kinetics cannot be remotely modified and thus adapted to changing therapeutic needs. To overcome this issue, drug delivery systems able to respond to external stimuli are highly desirable, as they allow a high level of temporal and spatial control over drug release kinetics, in an operator-dependent fashion. Areas covered: On-demand drug delivery systems actually represent a frontier in this field and are attracting an increasing interest at both research and industrial level. Stimuli-responsive thin films, enabled by nanofillers, hold a tremendous potential in the field of triggerable drug delivery systems. The inclusion of responsive elements in homogeneous or heterogeneous thin film-shaped polymeric matrices strengthens and/or adds intriguing properties to conventional (bare) materials in film shape. Expert opinion: This Expert Opinion review aims to discuss the approaches currently pursued to achieve an effective on-demand drug delivery, through nanocomposite thin films. Different triggering mechanisms allowing a fine control on drug delivery are described, together with current challenges and possible future applications in therapy and surgery.

Virological diagnosis of Ebolavirus infection.

PubMed

Smith, D W; Rawlinson, W D; Kok, J; Dwyer, D E; Catton, M

2015-08-01

Ebolaviruses, and the other viral causes of haemorrhagic fevers (VHF) have always posed special problems for diagnostic laboratories. These arise from the rarity of human infections, minimal documented experience with test delivery and interpretation, the paucity of established commercial or in-house assays, the lack of clinical material for test development and validation, the high level containment required for handling live virus, the ongoing evolution of the viruses, and the high personal and public health requirements for accurate diagnosis. This article addresses the current situation and the ongoing challenges associated with delivering timely, high quality and safe testing within Australia for people exposed as part of the current major outbreak of Ebolavirus disease (EVD) in Western Africa. The members of the Public Health Laboratory Network have developed deliverable and reliable nucleic acid detection tests, and also have the laboratory capacity to handle the live viruses if necessary. However delivering and maintaining these services necessitates high levels of experience in developing and applying tests for exotic and emerging infections, strong national and international links and collaborations, ongoing monitoring and reassessment of test design and performance, innovative approaches to generation of positive control material, and a regular quality assurance program.

Manufacturing recombinant proteins in kg-ton quantities using animal cells in bioreactors.

PubMed

De Jesus, Maria; Wurm, Florian M

2011-06-01

Mammalian cells in bioreactors as production host are the focus of this review. We wish to briefly describe today's technical status and to highlight emerging trends in the manufacture of recombinant therapeutic proteins, focusing on Chinese hamster ovary (CHO) cells. CHO cells are the manufacturing host system of choice for more than 70% of protein pharmaceuticals on the market [21]. The current global capacity to grow mammalian cells in bioreactors stands at about 0.5 million liters, whereby the largest vessels can have a working volume of about 20,000l. We are focusing in this article on the upstream part of protein manufacturing. Over the past 25 years, volumetric yields for recombinant cell lines have increased about 20-fold mainly as the result of improvements in media and bioprocess design. Future yield increases are expected to come from improved gene delivery methods, from improved, possibly genetically modified host systems, and from further improved bioprocesses in bioreactors. Other emerging trends in protein manufacturing that are discussed include the use of disposal bioreactors and transient gene expression. We specifically highlight here current research in our own laboratories. Copyright © 2011 Elsevier B.V. All rights reserved.

Biodegradable nanoparticles as theranostics of ovarian cancer: an overview.

PubMed

Chaurasiya, Swati; Mishra, Vijay

2018-04-01

Above 10 million people are suffering from cancers every year. As per American Cancer Society, more than 22 440 new cases and 14 080 deaths were reported from ovarian cancer yearly worldwide. This review explores the current status, challenges and future perspectives of tumour-targeted theranostic nanoparticles (NPs). Most of the ovarian malignancy cases are uncovered after the disease is in a difficult state due to poor screening techniques and non-specific symptoms. In this manner, forceful and fruitful treatment is required that will indicate insignificant lethal impacts to solid tissue. In the current research, stealth biodegradable NPs are produced as vehicles for imaging and treatment of ovarian cancer as the controlled and targeted delivery of chemotherapeutic as well as imaging agents. To enhance the dependability of the colloidal suspension as well as to increase their circulation lifetime, NPs are introduced by incorporating the functional poly(ethylene glycol) on their surface, which also provides a site to conjugation of focusing on agents to ovarian tissue. Biodegradable theranostic NPs can be fabricated and surface engineered without any alteration in drug-loading capacity, safety and efficacy. These NPs have shown promising results in imaging as well as treatment of ovarian cancer. © 2018 Royal Pharmaceutical Society.

Current warming will reduce yields unless maize breeding and seed systems adapt immediately

NASA Astrophysics Data System (ADS)

Challinor, A. J.; Koehler, A.-K.; Ramirez-Villegas, J.; Whitfield, S.; Das, B.

2016-10-01

The development of crop varieties that are better suited to new climatic conditions is vital for future food production. Increases in mean temperature accelerate crop development, resulting in shorter crop durations and reduced time to accumulate biomass and yield. The process of breeding, delivery and adoption (BDA) of new maize varieties can take up to 30 years. Here, we assess for the first time the implications of warming during the BDA process by using five bias-corrected global climate models and four representative concentration pathways with realistic scenarios of maize BDA times in Africa. The results show that the projected difference in temperature between the start and end of the maize BDA cycle results in shorter crop durations that are outside current variability. Both adaptation and mitigation can reduce duration loss. In particular, climate projections have the potential to provide target elevated temperatures for breeding. Whilst options for reducing BDA time are highly context dependent, common threads include improved recording and sharing of data across regions for the whole BDA cycle, streamlining of regulation, and capacity building. Finally, we show that the results have implications for maize across the tropics, where similar shortening of duration is projected.

Virological diagnosis of Ebolavirus infection

PubMed Central

Smith, D. W.; Rawlinson, W. D.; Kok, J.; Dwyer, D. E.; Catton, M.

2015-01-01

Summary Ebolaviruses, and the other viral causes of haemorrhagic fevers (VHF) have always posed special problems for diagnostic laboratories. These arise from the rarity of human infections, minimal documented experience with test delivery and interpretation, the paucity of established commercial or in-house assays, the lack of clinical material for test development and validation, the high level containment required for handling live virus, the ongoing evolution of the viruses, and the high personal and public health requirements for accurate diagnosis. This article addresses the current situation and the ongoing challenges associated with delivering timely, high quality and safe testing within Australia for people exposed as part of the current major outbreak of Ebolavirus disease (EVD) in Western Africa. The members of the Public Health Laboratory Network have developed deliverable and reliable nucleic acid detection tests, and also have the laboratory capacity to handle the live viruses if necessary. However delivering and maintaining these services necessitates high levels of experience in developing and applying tests for exotic and emerging infections, strong national and international links and collaborations, ongoing monitoring and reassessment of test design and performance, innovative approaches to generation of positive control material, and a regular quality assurance program. PMID:26126050

Capacity building for critical care training delivery: Development and evaluation of the Network for Improving Critical care Skills Training (NICST) programme in Sri Lanka.

PubMed

Stephens, Tim; De Silva, A Pubudu; Beane, Abi; Welch, John; Sigera, Chathurani; De Alwis, Sunil; Athapattu, Priyantha; Dharmagunawardene, Dilantha; Peiris, Lalitha; Siriwardana, Somalatha; Abeynayaka, Ashoka; Jayasinghe, Kosala Saroj Amarasena; Mahipala, Palitha G; Dondorp, Arjen; Haniffa, Rashan

2017-04-01

To deliver and evaluate a short critical care nurse training course whilst simultaneously building local training capacity. A multi-modal short course for critical care nursing skills was delivered in seven training blocks, from 06/2013-11/2014. Each training block included a Train the Trainer programme. The project was evaluated using Kirkpatrick's Hierarchy of Learning. There was a graded hand over of responsibility for course delivery from overseas to local faculty between 2013 and 2014. Sri Lanka. Participant learning assessed through pre/post course Multi-Choice Questionnaires. A total of 584 nurses and 29 faculty were trained. Participant feedback was consistently positive and each course demonstrated a significant increase (p≤0.0001) in MCQ scores. There was no significant difference MCQ scores (p=0.186) between overseas faculty led and local faculty led courses. In a relatively short period, training with good educational outcomes was delivered to nearly 25% of the critical care nursing population in Sri Lanka whilst simultaneously building a local faculty of trainers. Through use of a structured Train the Trainer programme, course outcomes were maintained following the handover of training responsibility to Sri Lankan faculty. The focus on local capacity building increases the possibility of long term course sustainability. Copyright © 2016 Elsevier Ltd. All rights reserved.

Building leadership capacity through peer career coaching: a case study.

PubMed

Sabo, Kathy; Duff, Margaret; Purdy, Brendan

2008-01-01

Today's demanding healthcare environment requires resiliency, creativity and innovation in delivery of patient care and service. Hospitals must create a workplace where staff are supported to develop professionally as knowledge workers. In 2003, University Health Network (UHN) partnered with donnerwheeler, career planning and development consultants, to provide a program for its 2,700 registered nurses. One component of this project, a peer coaching program called Coach Mastery, is profiled in this case study, which describes how it was implemented and the successes, challenges and outcomes in building internal leadership capacity and supporting staff development through career planning and development.

78 FR 67211 - Notice of Request for the Extension of a Currently Approved Information Collection

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-08

... Certifications and Assurances, that they will comply with pre-award and post-delivery audit requirements for..., Post-Delivery Audit Requirements Under Buy America DATES: Comments must be submitted before January 7... through Friday, except federal holidays. FOR FURTHER INFORMATION CONTACT: Pre-Award, Post-Delivery Audit...

pH-Responsive carriers for oral drug delivery: challenges and opportunities of current platforms.

PubMed

Liu, Lin; Yao, WenDong; Rao, YueFeng; Lu, XiaoYang; Gao, JianQing

2017-11-01

Oral administration is a desirable alternative of parenteral administration due to the convenience and increased compliance to patients, especially for chronic diseases that require frequent administration. The oral drug delivery is a dynamic research field despite the numerous challenges limiting their effective delivery, such as enzyme degradation, hydrolysis and low permeability of intestinal epithelium in the gastrointestinal (GI) tract. pH-Responsive carriers offer excellent potential as oral therapeutic systems due to enhancing the stability of drug delivery in stomach and achieving controlled release in intestines. This review provides a wide perspective on current status of pH-responsive oral drug delivery systems prepared mainly with organic polymers or inorganic materials, including the strategies used to overcome GI barriers, the challenges in their development and future prospects, with focus on technology trends to improve the bioavailability of orally delivered drugs, the mechanisms of drug release from pH-responsive oral formulations, and their application for drug delivery, such as protein and peptide therapeutics, vaccination, inflammatory bowel disease (IBD) and bacterial infections.

Biomaterials for the Treatment of Alzheimer's Disease.

PubMed

Hadavi, Darya; Poot, André A

2016-01-01

Alzheimer's disease (AD) as a progressive and fatal neurodegenerative disease represents a huge unmet need for treatment. The low efficacy of current treatment methods is not only due to low drug potency but also due to the presence of various obstacles in the delivery routes. One of the main barriers is the blood-brain barrier. The increasing prevalence of AD and the low efficacy of current therapies have increased the amount of research on unraveling of disease pathways and development of treatment strategies. One of the interesting areas for the latter subject is biomaterials and their applications. This interest originates from the fact that biomaterials are very useful for the delivery of therapeutic agents, such as drugs, proteins, and/or cells, in order to treat diseases and regenerate tissues. Recently, manufacturing of nano-sized delivery systems has increased the efficacy and delivery potential of biomaterials. In this article, we review the latest developments with regard to the use of biomaterials for the treatment of AD, including nanoparticles and liposomes for delivery of therapeutic compounds and scaffolds for cell delivery strategies.

Transdermal patches: history, development and pharmacology.

PubMed

Pastore, Michael N; Kalia, Yogeshvar N; Horstmann, Michael; Roberts, Michael S

2015-05-01

Transdermal patches are now widely used as cosmetic, topical and transdermal delivery systems. These patches represent a key outcome from the growth in skin science, technology and expertise developed through trial and error, clinical observation and evidence-based studies that date back to the first existing human records. This review begins with the earliest topical therapies and traces topical delivery to the present-day transdermal patches, describing along the way the initial trials, devices and drug delivery systems that underpin current transdermal patches and their actives. This is followed by consideration of the evolution in the various patch designs and their limitations as well as requirements for actives to be used for transdermal delivery. The properties of and issues associated with the use of currently marketed products, such as variability, safety and regulatory aspects, are then described. The review concludes by examining future prospects for transdermal patches and drug delivery systems, such as the combination of active delivery systems with patches, minimally invasive microneedle patches and cutaneous solutions, including metered-dose systems. © 2015 The British Pharmacological Society.

Sodium dependent multivitamin transporter (SMVT): a potential target for drug delivery.

PubMed

Vadlapudi, Aswani Dutt; Vadlapatla, Ramya Krishna; Mitra, Ashim K

2012-06-01

Sodium dependent multivitamin transporter (SMVT; product of the SLC5A6 gene) is an important transmembrane protein responsible for translocation of vitamins and other essential cofactors such as biotin, pantothenic acid and lipoic acid. Hydropathy plot (Kyte-Dolittle algorithm) revealed that human SMVT protein consists of 635 amino acids and 12 transmembrane domains with both amino and carboxyl termini oriented towards the cytoplasm. SMVT is expressed in various tissues such as placenta, intestine, brain, liver, lung, kidney, cornea, retina and heart. This transporter displays broad substrate specificity and excellent capacity for utilization in drug delivery. Drug absorption is often limited by the presence of physiological (epithelial tight junctions), biochemical (efflux transporters and enzymatic degradation) and chemical (size, lipophilicity, molecular weight, charge etc.) barriers. These barriers may cause many potential therapeutics to be dropped from the preliminary screening portfolio and subsequent entry into the market. Transporter targeted delivery has become a powerful approach to deliver drugs to target tissues because of the ability of the transporter to translocate the drug to intracellular organelles at a higher rate. This review highlights studies employing SMVT transporter as a target for drug delivery to improve bioavailability and investigate the feasibility of developing SMVT targeted drug delivery systems.

Core-shell designs of photoluminescent nanodiamonds with porous silica coatings for bioimaging and drug delivery II: application.

PubMed

Prabhakar, Neeraj; Näreoja, Tuomas; von Haartman, Eva; Karaman, Didem Şen; Jiang, Hua; Koho, Sami; Dolenko, Tatiana A; Hänninen, Pekka E; Vlasov, Denis I; Ralchenko, Victor G; Hosomi, Satoru; Vlasov, Igor I; Sahlgren, Cecilia; Rosenholm, Jessica M

2013-05-07

Recent advances within materials science and its interdisciplinary applications in biomedicine have emphasized the potential of using a single multifunctional composite material for concurrent drug delivery and biomedical imaging. Here we present a novel composite material consisting of a photoluminescent nanodiamond (ND) core with a porous silica (SiO2) shell. This novel multifunctional probe serves as an alternative nanomaterial to address the existing problems with delivery and subsequent tracing of the particles. Whereas the unique optical properties of ND allows for long-term live cell imaging and tracking of cellular processes, mesoporous silica nanoparticles (MSNs) have proven to be efficient drug carriers. The advantages of both ND and MSNs were hereby integrated in the new composite material, ND@MSN. The optical properties provided by the ND core rendered the nanocomposite suitable for microscopy imaging in fluorescence and reflectance mode, as well as super-resolution microscopy as a STED label; whereas the porous silica coating provided efficient intracellular delivery capacity, especially in surface-functionalized form. This study serves as a demonstration how this novel nanomaterial can be exploited for both bioimaging and drug delivery for future theranostic applications.

Umbrella project for Bangladesh: strengthening NGO capacity and linkages to improve reproductive health service and information. RAS/98/P55.

PubMed

1999-06-01

In Bangladesh, the UN Population Fund is working to strengthen nongovernmental organization (NGO) capacity and linkages to improve reproductive health services and information. Specifically, the aim is to strengthen the technical and human resource capacity of participating NGOs and the functional linkages between national NGOs and relevant government agencies to help harmonize and standardize the delivery of reproductive health information and services. This umbrella project collaborates with RHI-participating NGOs in a policy paper on adolescent reproductive health, and will maintain contact with the regional dimension project to collaborate its activities. Programs implemented by partner NGOs are being reviewed and monitored, and linkages among national NGOs and government agencies are being developed. The main activities of the project are enumerated.

Storage capacity: how big should it be

DOE Office of Scientific and Technical Information (OSTI.GOV)

Malina, M.A.

1980-01-28

A mathematical model was developed for determining the economically optimal storage capacity of a given material or product at a manufacturing plant. The optimum was defined as a trade-off between the inventory-holding costs and the cost of customer-service failures caused by insufficient stocks for a peak-demand period. The order-arrival, production, storage, and shipment process was simulated by Monte Carlo techniques to calculate the probability of order delays for various lengths of time as a function of storage capacity. Example calculations for the storage of a bulk liquid chemical in tanks showed that the conclusions arrived at, via this model, aremore » comparatively insensitive to errors made in estimating the capital cost of storage or the risk of losing an order because of a late delivery.« less

Learning from the Youth Opportunity Experience: Building Delivery Capacity in Distressed Communities

ERIC Educational Resources Information Center

Harris, Linda

2006-01-01

In May 2000, the United States Department of Labor awarded sizable Youth Opportunity (YO) Grants to 36 high-poverty urban, rural, and Native American communities. These communities were among the most economically distressed communities in the nation, all characterized by high drop out rates, high youth unemployment rates, greater incidence of…

Active Implementation Frameworks for Successful Service Delivery: Catawba County Child Wellbeing Project

ERIC Educational Resources Information Center

Metz, Allison; Bartley, Leah; Ball, Heather; Wilson, Dawn; Naoom, Sandra; Redmond, Phil

2015-01-01

Traditional approaches to disseminating research based programs and innovations for children and families, which rely on practitioners and policy makers to make sense of research on their own, have been found insufficient. There is growing interest in strategies that "make it happen" by actively building the capacity of service providers…

Education for Sustainable Development: Enhancing Climate Change Adaptation Expertise in Developing Countries

ERIC Educational Resources Information Center

Fahey, Shireen; Verstraten, Luke; Berry, Ashton J.

2016-01-01

This article presents the results of an innovative education capacity assessment and delivery project to promote sustainable development in large ocean states in the Western Indian Ocean (WIO) region. Science education can help prepare the present and coming generations for stability in an uncertain future. Limited financial, geographical and…

STANDALONE &LDQUO;GREEN&RDQUO; COMMUNITY-CENTER BUILDINGS: HYDROGEN GENERATION/STORAGE/DELIVERY SYSTEM FOR WHEN PRIMARY ENERGY STORAGE IS AT CAPACITY

EPA Science Inventory

Overall, the implementation of a computer-controlled hydrogen generation system and subsequent conversion of small engine equipment for hydrogen use has been surprisingly straightforward from an engineering and technology standpoint. More testing is required to get a better gr...

75 FR 19990 - Lake Casitas Resource Management Plan, Ventura County, CA

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-16

... RMP would: (1) Ensure safe storage and timely delivery of high-quality water to users while enhancing..., California. The dam, which stores water for irrigation, municipal and industrial use within the Casitas Municipal Water District (CMWD), was completed in November 1958. Lake Casitas has a storage capacity of 254...

Linking Flexible Delivery and Community Development: The Wugularr Story. Occasional Paper

ERIC Educational Resources Information Center

Anderson, Stuart

2009-01-01

Building the research capacity of the vocational education and training (VET) sector is a key concern for the National Centre for Vocational Education Research (NCVER). To assist with this objective, NCVER supports an academic scholarship program, whereby VET practitioners are sponsored to undertake university study at honours', master's or…

Resource Management and Risk Mitigation in Online Storage Grids

ERIC Educational Resources Information Center

Du, Ye

2010-01-01

This dissertation examines the economic value of online storage resources that could be traded and shared as potential commodities and the consequential investments and deployment of such resources. The value proposition of emergent business models such as Akamai and Amazon S3 in online storage grids is capacity provision and content delivery at…

Assessment of system reliability for a stochastic-flow distribution network with the spoilage property

NASA Astrophysics Data System (ADS)

Lin, Yi-Kuei; Huang, Cheng-Fu; Yeh, Cheng-Ta

2016-04-01

In supply chain management, satisfying customer demand is the most concerned for the manager. However, the goods may rot or be spoilt during delivery owing to natural disasters, inclement weather, traffic accidents, collisions, and so on, such that the intact goods may not meet market demand. This paper concentrates on a stochastic-flow distribution network (SFDN), in which a node denotes a supplier, a transfer station, or a market, while a route denotes a carrier providing the delivery service for a pair of nodes. The available capacity of the carrier is stochastic because the capacity may be partially reserved by other customers. The addressed problem is to evaluate the system reliability, the probability that the SFDN can satisfy the market demand with the spoilage rate under the budget constraint from multiple suppliers to the customer. An algorithm is developed in terms of minimal paths to evaluate the system reliability along with a numerical example to illustrate the solution procedure. A practical case of fruit distribution is presented accordingly to emphasise the management implication of the system reliability.