Sample records for accurate sobp delivery

  1. Commissioning a passive-scattering proton therapy nozzle for accurate SOBP delivery.

    PubMed

    Engelsman, M; Lu, H M; Herrup, D; Bussiere, M; Kooy, H M

    2009-06-01

    Proton radiotherapy centers that currently use passively scattered proton beams do field specific calibrations for a non-negligible fraction of treatment fields, which is time and resource consuming. Our improved understanding of the passive scattering mode of the IBA universal nozzle, especially of the current modulation function, allowed us to re-commission our treatment control system for accurate delivery of SOBPs of any range and modulation, and to predict the output for each of these fields. We moved away from individual field calibrations to a state where continued quality assurance of SOBP field delivery is ensured by limited system-wide measurements that only require one hour per week. This manuscript reports on a protocol for generation of desired SOBPs and prediction of dose output.

  2. Commissioning a passive-scattering proton therapy nozzle for accurate SOBP delivery

    PubMed Central

    Engelsman, M.; Lu, H.-M.; Herrup, D.; Bussiere, M.; Kooy, H. M.

    2009-01-01

    Proton radiotherapy centers that currently use passively scattered proton beams do field specific calibrations for a non-negligible fraction of treatment fields, which is time and resource consuming. Our improved understanding of the passive scattering mode of the IBA universal nozzle, especially of the current modulation function, allowed us to re-commission our treatment control system for accurate delivery of SOBPs of any range and modulation, and to predict the output for each of these fields. We moved away from individual field calibrations to a state where continued quality assurance of SOBP field delivery is ensured by limited system-wide measurements that only require one hour per week. This manuscript reports on a protocol for generation of desired SOBPs and prediction of dose output. PMID:19610306

  3. MO-F-CAMPUS-T-03: Verification of Range, SOBP Width, and Output for Passive-Scattering Proton Beams Using a Liquid Scintillator Detector

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

    Henry, T; Robertson, D; Therriault-Proulx, F

    2015-06-15

    Purpose: Liquid scintillators have been shown to provide fast and high-resolution measurements of radiation beams. However, their linear energy transfer-dependent response (quenching) limits their use in proton beams. The purpose of this study was to develop a simple and fast method to verify the range, spread-out Bragg peak (SOBP) width, and output of a passive-scattering proton beam with a liquid scintillator detector, without the need for quenching correction. Methods: The light signal from a 20×20×20 cm3 liquid scintillator tank was collected with a CCD camera. Reproducible landmarks on the SOBP depth-light curve were identified which possessed a linear relationship withmore » the beam range and SOBP width. The depth-light profiles for three beam energies (140, 160 and 180 MeV) with six SOBP widths at each energy were measured with the detector. Beam range and SOBP width calibration factors were obtained by comparing the depth-light curve landmarks with the nominal range and SOBP width for each beam setting. The daily output stability of the liquid scintillator detector was also studied by making eight repeated output measurements in a cobalt-60 beam over the course of two weeks. Results: The mean difference between the measured and nominal beam ranges was 0.6 mm (σ=0.2 mm), with a maximum difference of 0.9 mm. The mean difference between the measured and nominal SOBP widths was 0.1 mm (σ=1.8 mm), with a maximum difference of 4.0 mm. Finally an output variation of 0.14% was observed for 8 measurements performed over 2 weeks. Conclusion: A method has been developed to determine the range and SOBP width of a passive-scattering proton beam in a liquid scintillator without the need for quenching correction. In addition to providing rapid and accurate beam range and SOBP measurements, the detector is capable of measuring the output consistency with a high degree of precision. This project was supported in part by award number CA182450 from the National Cancer

  4. Development of an irradiation method with lateral modulation of SOBP width using a cone-type filter for carbon ion beams.

    PubMed

    Ishizaki, Azusa; Ishii, Keizo; Kanematsu, Nobuyuki; Kanai, Tatsuaki; Yonai, Shunsuke; Kase, Yuki; Takei, Yuka; Komori, Masataka

    2009-06-01

    Passive irradiation methods deliver an extra dose to normal tissues upstream of the target tumor, while in dynamic irradiation methods, interplay effects between dynamic beam delivery and target motion induced by breathing or respiration distort the dose distributions. To solve the problems of those two irradiation methods, the authors have developed a new method that laterally modulates the spread-out Bragg peak (SOBP) width. By reducing scanning in the depth direction, they expect to reduce the interplay effects. They have examined this new irradiation method experimentally. In this system, they used a cone-type filter that consisted of 400 cones in a grid of 20 cones by 20 cones. There were five kinds of cones with different SOBP widths arranged on the frame two dimensionally to realize lateral SOBP modulation. To reduce the number of steps of cones, they used a wheel-type filter to make minipeaks. The scanning intensity was modulated for each SOBP width with a pair of scanning magnets. In this experiment, a stepwise dose distribution and spherical dose distribution of 60 mm in diameter were formed. The nonflatness of the stepwise dose distribution was 5.7% and that of the spherical dose distribution was 3.8%. A 2 mm misalignment of the cone-type filter resulted in a nonflatness of more than 5%. Lateral SOBP modulation with a cone-type filter and a scanned carbon ion beam successfully formed conformal dose distribution with nonflatness of 3.8% for the spherical case. The cone-type filter had to be set to within 1 mm accuracy to maintain nonflatness within 5%. This method will be useful to treat targets moving during breathing and targets in proximity to important organs.

  5. SU-E-T-161: SOBP Beam Analysis Using Light Output of Scintillation Plate Acquired by CCD Camera.

    PubMed

    Cho, S; Lee, S; Shin, J; Min, B; Chung, K; Shin, D; Lim, Y; Park, S

    2012-06-01

    To analyze Bragg-peak beams in SOBP (spread-out Bragg-peak) beam using CCD (charge-coupled device) camera - scintillation screen system. We separated each Bragg-peak beam using light output of high sensitivity scintillation material acquired by CCD camera and compared with Bragg-peak beams calculated by Monte Carlo simulation. In this study, CCD camera - scintillation screen system was constructed with a high sensitivity scintillation plate (Gd2O2S:Tb) and a right-angled prismatic PMMA phantom, and a Marlin F-201B, EEE-1394 CCD camera. SOBP beam irradiated by the double scattering mode of a PROTEUS 235 proton therapy machine in NCC is 8 cm width, 13 g/cm 2 range. The gain, dose rate and current of this beam is 50, 2 Gy/min and 70 nA, respectively. Also, we simulated the light output of scintillation plate for SOBP beam using Geant4 toolkit. We evaluated the light output of high sensitivity scintillation plate according to intergration time (0.1 - 1.0 sec). The images of CCD camera during the shortest intergration time (0.1 sec) were acquired automatically and randomly, respectively. Bragg-peak beams in SOBP beam were analyzed by the acquired images. Then, the SOBP beam used in this study was calculated by Geant4 toolkit and Bragg-peak beams in SOBP beam were obtained by ROOT program. The SOBP beam consists of 13 Bragg-peak beams. The results of experiment were compared with that of simulation. We analyzed Bragg-peak beams in SOBP beam using light output of scintillation plate acquired by CCD camera and compared with that of Geant4 simulation. We are going to study SOBP beam analysis using more effective the image acquisition technique. © 2012 American Association of Physicists in Medicine.

  6. SOBP Is Mutated in Syndromic and Nonsyndromic Intellectual Disability and Is Highly Expressed in the Brain Limbic System

    PubMed Central

    Birk, Efrat; Har-Zahav, Adi; Manzini, Chiara M.; Pasmanik-Chor, Metsada; Kornreich, Liora; Walsh, Christopher A.; Noben-Trauth, Konrad; Albin, Adi; Simon, Amos J.; Colleaux, Laurence; Morad, Yair; Rainshtein, Limor; Tischfield, David J.; Wang, Peter; Magal, Nurit; Maya, Idit; Shoshani, Noa; Rechavi, Gideon; Gothelf, Doron; Maydan, Gal; Shohat, Mordechai; Basel-Vanagaite, Lina

    2010-01-01

    Intellectual disability (ID) affects 1%–3% of the general population. We recently reported on a family with autosomal-recessive mental retardation with anterior maxillary protrusion and strabismus (MRAMS) syndrome. One of the reported patients with ID did not have dysmorphic features but did have temporal lobe epilepsy and psychosis. We report on the identification of a truncating mutation in the SOBP that is responsible for causing both syndromic and nonsyndromic ID in the same family. The protein encoded by the SOBP, sine oculis binding protein ortholog, is a nuclear zinc finger protein. In mice, Sobp (also known as Jxc1) is critical for patterning of the organ of Corti; one of our patients has a subclinical cochlear hearing loss but no gross cochlear abnormalities. In situ RNA expression studies in postnatal mouse brain showed strong expression in the limbic system at the time interval of active synaptogenesis. The limbic system regulates learning, memory, and affective behavior, but limbic circuitry expression of other genes mutated in ID is unusual. By comparing the protein content of the +/jc to jc/jc mice brains with the use of proteomics, we detected 24 proteins with greater than 1.5-fold differences in expression, including two interacting proteins, dynamin and pacsin1. This study shows mutated SOBP involvement in syndromic and nonsyndromic ID with psychosis in humans. PMID:21035105

  7. Spot-scanning beam delivery with laterally- and longitudinally-mixed spot size pencil beams in heavy ion radiotherapy

    NASA Astrophysics Data System (ADS)

    Yan, Yuan-Lin; Liu, Xin-Guo; Dai, Zhong-Ying; Ma, Yuan-Yuan; He, Peng-Bo; Shen, Guo-Sheng; Ji, Teng-Fei; Zhang, Hui; Li, Qiang

    2017-09-01

    The three-dimensional (3D) spot-scanning method is one of the most commonly used irradiation methods in charged particle beam radiotherapy. Generally, spot-scanning beam delivery utilizes the same size pencil beam to irradiate the tumor targets. Here we propose a spot-scanning beam delivery method with laterally- and longitudinally-mixed size pencil beams for heavy ion radiotherapy. This uses pencil beams with a bigger spot size in the lateral direction and wider mini spread-out Bragg peak (mini-SOBP) to irradiate the inner part of a target volume, and pencil beams with a smaller spot size in the lateral direction and narrower mini-SOBP to irradiate the peripheral part of the target volume. Instead of being controlled by the accelerator, the lateral size of the pencil beam was adjusted by inserting Ta scatterers in the beam delivery line. The longitudinal size of the pencil beam (i.e. the width of the mini-SOBP) was adjusted by tilting mini ridge filters along the beam direction. The new spot-scanning beam delivery using carbon ions was investigated theoretically and compared with traditional spot-scanning beam delivery. Our results show that the new spot-scanning beam delivery has smaller lateral penumbra, steeper distal dose fall-off and the dose homogeneity (1-standard deviation/mean) in the target volume is better than 95%. Supported by Key Project of National Natural Science Foundation of China (U1232207), National Key Technology Support Program of the Ministry of Science and Technology of China (2015BAI01B11), National Key Research and Development Program of the Ministry of Science and Technology of China (2016YFC0904602) and National Natural Science Foundation of China (11075191, 11205217, 11475231, 11505249)

  8. Technical Note: Using experimentally determined proton spot scanning timing parameters to accurately model beam delivery time.

    PubMed

    Shen, Jiajian; Tryggestad, Erik; Younkin, James E; Keole, Sameer R; Furutani, Keith M; Kang, Yixiu; Herman, Michael G; Bues, Martin

    2017-10-01

    To accurately model the beam delivery time (BDT) for a synchrotron-based proton spot scanning system using experimentally determined beam parameters. A model to simulate the proton spot delivery sequences was constructed, and BDT was calculated by summing times for layer switch, spot switch, and spot delivery. Test plans were designed to isolate and quantify the relevant beam parameters in the operation cycle of the proton beam therapy delivery system. These parameters included the layer switch time, magnet preparation and verification time, average beam scanning speeds in x- and y-directions, proton spill rate, and maximum charge and maximum extraction time for each spill. The experimentally determined parameters, as well as the nominal values initially provided by the vendor, served as inputs to the model to predict BDTs for 602 clinical proton beam deliveries. The calculated BDTs (T BDT ) were compared with the BDTs recorded in the treatment delivery log files (T Log ): ∆t = T Log -T BDT . The experimentally determined average layer switch time for all 97 energies was 1.91 s (ranging from 1.9 to 2.0 s for beam energies from 71.3 to 228.8 MeV), average magnet preparation and verification time was 1.93 ms, the average scanning speeds were 5.9 m/s in x-direction and 19.3 m/s in y-direction, the proton spill rate was 8.7 MU/s, and the maximum proton charge available for one acceleration is 2.0 ± 0.4 nC. Some of the measured parameters differed from the nominal values provided by the vendor. The calculated BDTs using experimentally determined parameters matched the recorded BDTs of 602 beam deliveries (∆t = -0.49 ± 1.44 s), which were significantly more accurate than BDTs calculated using nominal timing parameters (∆t = -7.48 ± 6.97 s). An accurate model for BDT prediction was achieved by using the experimentally determined proton beam therapy delivery parameters, which may be useful in modeling the interplay effect and patient throughput. The model may

  9. TH-CD-201-10: Highly Efficient Synchronized High-Speed Scintillation Camera System for Measuring Proton Range, SOBP and Dose Distributions in a 2D-Plane

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

    Goddu, S; Sun, B; Grantham, K

    2016-06-15

    Purpose: Proton therapy (PT) delivery is complex and extremely dynamic. Therefore, quality assurance testing is vital, but highly time-consuming. We have developed a High-Speed Scintillation-Camera-System (HS-SCS) for simultaneously measuring multiple beam characteristics. Methods: High-speed camera was placed in a light-tight housing and dual-layer neutron shield. HS-SCS is synchronized with a synchrocyclotron to capture individual proton-beam-pulses (PBPs) at ∼504 frames/sec. The PBPs from synchrocyclotron trigger the HS-SCS to open its shutter for programmed exposure-time. Light emissions within 30×30×5cm3 plastic-scintillator (BC-408) were captured by a CCD-camera as individual images revealing dose-deposition in a 2D-plane with a resolution of 0.7mm for range andmore » SOBP measurements and 1.67mm for profiles. The CCD response as well as signal to noise ratio (SNR) was characterized for varying exposure times, gains for different light intensities using a TV-Optoliner system. Software tools were developed to analyze ∼5000 images to extract different beam parameters. Quenching correction-factors were established by comparing scintillation Bragg-Peaks with water scanned ionization-chamber measurements. Quenching corrected Bragg-peaks were integrated to ascertain proton-beam range (PBR), width of Spared-Out-Bragg-Peak (MOD) and distal.« less

  10. Evaluation of beam delivery and ripple filter design for non-isocentric proton and carbon ion therapy.

    PubMed

    Grevillot, L; Stock, M; Vatnitsky, S

    2015-10-21

    This study aims at selecting and evaluating a ripple filter design compatible with non-isocentric proton and carbon ion scanning beam treatment delivery for a compact nozzle. The use of non-isocentric treatments when the patient is shifted as close as possible towards the nozzle exit allows for a reduction in the air gap and thus an improvement in the quality of scanning proton beam treatment delivery. Reducing the air gap is less important for scanning carbon ions, but ripple filters are still necessary for scanning carbon ion beams to reduce the number of energy steps required to deliver homogeneous SOBP. The proper selection of ripple filters also allows a reduction in the possible transverse and depth-dose inhomogeneities that could appear in non-isocentric conditions in particular. A thorough review of existing ripple filter designs over the past 16 years is performed and a design for non-isocentric treatment delivery is presented. A unique ripple filter quality index (QIRiFi) independent of the particle type and energy and representative of the ratio between energy modulation and induced scattering is proposed. The Bragg peak width evaluated at the 80% dose level (BPW80) is proposed to relate the energy modulation of the delivered Bragg peaks and the energy layer step size allowing the production of homogeneous SOBP. Gate/Geant4 Monte Carlo simulations have been validated for carbon ion and ripple filter simulations based on measurements performed at CNAO and subsequently used for a detailed analysis of the proposed ripple filter design. A combination of two ripple filters in a series has been validated for non-isocentric delivery and did not show significant transverse and depth-dose inhomogeneities. Non-isocentric conditions allow a significant reduction in the spot size at the patient entrance (up to 350% and 200% for protons and carbon ions with range shifter, respectively), and therefore in the lateral penumbra in the patients.

  11. The development of accurate and high quality radiotherapy treatment delivery

    NASA Astrophysics Data System (ADS)

    Griffiths, Susan E.

    Accurate radiotherapy delivery is required for curing cancer. Historical radiotherapy accuracy studies at Leeds (1983-1991) are discussed in context of when radiographers were not involved in practice design. The seminal research was unique in being led by a radiographer practitioner, and in prospectively studying the accuracy of different techniques within one department. The viability of alignment of treatment beams with marks painted on a patient's skin varied daily, and, using film I showed that the alignment of treatment on anatomy varied. I then led 6 sequential studies with collaborating oncologists. Unique outcomes were in identifying the origins of treatment inaccuracies, implementing and evidencing changes in multi-disciplinary practice, thus improving accuracy and reproducibility generally and achieving accuracy for the pelvis to within current norms. Innovations included: discontinuation of painted skin marks and developing whole-body patient positioning using lasers, tattoos, and standardised supports; unification of set-up conditions through planning and treatment; planning normal tissue margins round target tissue to allow for inaccuracies (1985); improved manual shielding methods, changed equipment usage, its quality assurance and design; influenced the development of portal imaging and image analysis. Consequences and current implications. The research, still cited internationally, contributed to clinical management of lymphoma, and critically underpins contemporary practice. It led to my becoming the first radiographer invited into multi-disciplinary collaborative work, to advise in the first multi-centre clinical trials to consider treatment delivery accuracy, contribute to books written from within other disciplines and inform guidelines for good practice so helping to improve practices, with recent publications. I thus led my profession into research activity. Later work included development of a national staffing formula for radiotherapy

  12. Modeling the biophysical effects in a carbon beam delivery line by using Monte Carlo simulations

    NASA Astrophysics Data System (ADS)

    Cho, Ilsung; Yoo, SeungHoon; Cho, Sungho; Kim, Eun Ho; Song, Yongkeun; Shin, Jae-ik; Jung, Won-Gyun

    2016-09-01

    The Relative biological effectiveness (RBE) plays an important role in designing a uniform dose response for ion-beam therapy. In this study, the biological effectiveness of a carbon-ion beam delivery system was investigated using Monte Carlo simulations. A carbon-ion beam delivery line was designed for the Korea Heavy Ion Medical Accelerator (KHIMA) project. The GEANT4 simulation tool kit was used to simulate carbon-ion beam transport into media. An incident energy carbon-ion beam with energy in the range between 220 MeV/u and 290 MeV/u was chosen to generate secondary particles. The microdosimetric-kinetic (MK) model was applied to describe the RBE of 10% survival in human salivary-gland (HSG) cells. The RBE weighted dose was estimated as a function of the penetration depth in the water phantom along the incident beam's direction. A biologically photon-equivalent Spread Out Bragg Peak (SOBP) was designed using the RBE-weighted absorbed dose. Finally, the RBE of mixed beams was predicted as a function of the depth in the water phantom.

  13. Accurate Monte Carlo simulations for nozzle design, commissioning and quality assurance for a proton radiation therapy facility.

    PubMed

    Paganetti, H; Jiang, H; Lee, S Y; Kooy, H M

    2004-07-01

    Monte Carlo dosimetry calculations are essential methods in radiation therapy. To take full advantage of this tool, the beam delivery system has to be simulated in detail and the initial beam parameters have to be known accurately. The modeling of the beam delivery system itself opens various areas where Monte Carlo calculations prove extremely helpful, such as for design and commissioning of a therapy facility as well as for quality assurance verification. The gantry treatment nozzles at the Northeast Proton Therapy Center (NPTC) at Massachusetts General Hospital (MGH) were modeled in detail using the GEANT4.5.2 Monte Carlo code. For this purpose, various novel solutions for simulating irregular shaped objects in the beam path, like contoured scatterers, patient apertures or patient compensators, were found. The four-dimensional, in time and space, simulation of moving parts, such as the modulator wheel, was implemented. Further, the appropriate physics models and cross sections for proton therapy applications were defined. We present comparisons between measured data and simulations. These show that by modeling the treatment nozzle with millimeter accuracy, it is possible to reproduce measured dose distributions with an accuracy in range and modulation width, in the case of a spread-out Bragg peak (SOBP), of better than 1 mm. The excellent agreement demonstrates that the simulations can even be used to generate beam data for commissioning treatment planning systems. The Monte Carlo nozzle model was used to study mechanical optimization in terms of scattered radiation and secondary radiation in the design of the nozzles. We present simulations on the neutron background. Further, the Monte Carlo calculations supported commissioning efforts in understanding the sensitivity of beam characteristics and how these influence the dose delivered. We present the sensitivity of dose distributions in water with respect to various beam parameters and geometrical misalignments

  14. SU-E-T-14: Modeling of 3D Positron Emission Activity Distributions Induced by Proton Irradiation: A Semi-Empirical Method.

    PubMed

    Lopatiuk-Tirpak, O; Su, Z; Hsi, W; Zeidan, O; Meeks, S

    2012-06-01

    to present and validate a method for modeling three-dimensional positron emission (PE) activity distributions induced by proton beam irradiation for PET/CT delivery verification studies in homogeneous media. the method relies on modeling the 3D proton flux distribution by combining the analytical expression for the depth reduction of proton flux with the empirically obtained lateral distribution. The latter is extracted from the corresponding dose distribution under the assumption that the projectile energy is nearly constant in the lateral plane. The same assumption allows calculating the 3D induced activity distributions from proton flux distributions by parameterizing the energy-dependent activation cross-sections in terms of depth via the energy-range relation. Results of this modeling approach were validated against experimental PET/CT data from three phantom deliveries: unmodulated (pristine) beam, spread-out Bragg peak (SOBP) delivery without a range compensator, and SOBP with a range compensator. BANG3-Pro2 polymer gel was used as a phantom material because of its elemental soft-tissue equivalence. the agreement between modeled and measured activity distributions was evaluated using 3D gamma index analysis method, which, despite being traditionally reserved for dose distribution comparisons, is sufficiently general to be applied to other quantities. The evaluation criteria were dictated by limitations of PET imaging and were chosen to correspond to count rate uncertainty (6% value difference) and spatial resolution (4 mm distance to agreement). With these criteria and the threshold of 6%, the fraction of evaluated voxels passing the gamma evaluation was 97.9% for the pristine beam, 98.9% for the SOBP without compensator, and 98.5% for SOBP with compensator. results of gamma evaluation indicate that the activity distributions produced by the model are consistent with experimental data within the uncertainties of PET imaging for clinical proton beams

  15. Accurate Treatment of Collisions and Water-Delivery in Models of Terrestrial Planet Formation

    NASA Astrophysics Data System (ADS)

    Haghighipour, Nader; Maindl, Thomas; Schaefer, Christoph

    2017-10-01

    It is widely accepted that collisions among solid bodies, ignited by their interactions with planetary embryos is the key process in the formation of terrestrial planets and transport of volatiles and chemical compounds to their accretion zones. Unfortunately, due to computational complexities, these collisions are often treated in a rudimentary way. Impacts are considered to be perfectly inelastic and volatiles are considered to be fully transferred from one object to the other. This perfect-merging assumption has profound effects on the mass and composition of final planetary bodies as it grossly overestimates the masses of these objects and the amounts of volatiles and chemical elements transferred to them. It also entirely neglects collisional-loss of volatiles (e.g., water) and draws an unrealistic connection between these properties and the chemical structure of the protoplanetary disk (i.e., the location of their original carriers). We have developed a new and comprehensive methodology to simulate growth of embryos to planetary bodies where we use a combination of SPH and N-body codes to accurately model collisions as well as the transport/transfer of chemical compounds. Our methodology accounts for the loss of volatiles (e.g., ice sublimation) during the orbital evolution of their careers and accurately tracks their transfer from one body to another. Results of our simulations show that traditional N-body modeling of terrestrial planet formation overestimates the amount of the mass and water contents of the final planets by over 60% implying that not only the amount of water they suggest is far from being realistic, small planets such as Mars can also form in these simulations when collisions are treated properly. We will present details of our methodology and discuss its implications for terrestrial planet formation and water delivery to Earth.

  16. Articulating feedstock delivery device

    DOEpatents

    Jordan, Kevin

    2013-11-05

    A fully articulable feedstock delivery device that is designed to operate at pressure and temperature extremes. The device incorporates an articulating ball assembly which allows for more accurate delivery of the feedstock to a target location. The device is suitable for a variety of applications including, but not limited to, delivery of feedstock to a high-pressure reaction chamber or process zone.

  17. Profitable capitation requires accurate costing.

    PubMed

    West, D A; Hicks, L L; Balas, E A; West, T D

    1996-01-01

    In the name of costing accuracy, nurses are asked to track inventory use on per treatment basis when more significant costs, such as general overhead and nursing salaries, are usually allocated to patients or treatments on an average cost basis. Accurate treatment costing and financial viability require analysis of all resources actually consumed in treatment delivery, including nursing services and inventory. More precise costing information enables more profitable decisions as is demonstrated by comparing the ratio-of-cost-to-treatment method (aggregate costing) with alternative activity-based costing methods (ABC). Nurses must participate in this costing process to assure that capitation bids are based upon accurate costs rather than simple averages.

  18. Can Glucose Be Monitored Accurately at the Site of Subcutaneous Insulin Delivery?

    PubMed Central

    Castle, Jessica R.; Jacobs, Peter G.; Cargill, Robert S.

    2014-01-01

    Because insulin promotes glucose uptake into adipocytes, it has been assumed that during measurement of glucose at the site of insulin delivery, the local glucose level would be much lower than systemic glucose. However, recent investigations challenge this notion. What explanations could account for a reduced local effect of insulin in the subcutaneous space? One explanation is that, in humans, the effect of insulin on adipocytes appears to be small. Another is that insulin monomers and dimers (from hexamer disassociation) might be absorbed into the circulation before they can increase glucose uptake locally. In addition, negative cooperativity of insulin action (a lower than expected effect of very high insulin concentrations)may play a contributing role. Other factors to be considered include dilution of interstitial fluid by the insulin vehicle and the possibility that some of the local decline in glucose might be due to the systemic effect of insulin. With regard to future research, redundant sensing units might be able to quantify the effects of proximity, leading to a compensatory algorithm. In summary, when measured at the site of insulin delivery, the decline in subcutaneous glucose level appears to be minimal, though the literature base is not large. Findings thus far support (1) the development of integrated devices that monitor glucose and deliver insulin and (2) the use of such devices to investigate the relationship between subcutaneous delivery of insulin and its local effects on glucose. A reduction in the number of percutaneous devices needed to manage diabetes would be welcome. PMID:24876621

  19. Difference in the relative biological effectiveness and DNA damage repair processes in response to proton beam therapy according to the positions of the spread out Bragg peak.

    PubMed

    Hojo, Hidehiro; Dohmae, Takeshi; Hotta, Kenji; Kohno, Ryosuke; Motegi, Atsushi; Yagishita, Atsushi; Makinoshima, Hideki; Tsuchihara, Katsuya; Akimoto, Tetsuo

    2017-07-03

    Cellular responses to proton beam irradiation are not yet clearly understood, especially differences in the relative biological effectiveness (RBE) of high-energy proton beams depending on the position on the Spread-Out Bragg Peak (SOBP). Towards this end, we investigated the differences in the biological effect of a high-energy proton beam on the target cells placed at different positions on the SOBP, using two human esophageal cancer cell lines with differing radiosensitivities. Two human esophageal cancer cell lines (OE21, KYSE450) with different radiosensitivities were irradiated with a 235-MeV proton beam at 4 different positions on the SOBP (position #1: At entry; position #2: At the proximal end of the SOBP; position #3: Center of the SOBP; position #4: At the distal end of the SOBP), and the cell survivals were assessed by the clonogenic assay. The RBE 10 for each position of the target cell lines on the SOBP was determined based on the results of the cell survival assay conducted after photon beam irradiation. In addition, the number of DNA double-strand breaks was estimated by quantitating the number of phospho-histone H2AX (γH2AX) foci formed in the nuclei by immunofluorescence analysis. In regard to differences in the RBE of a proton beam according to the position on the SOBP, the RBE value tended to increase as the position on the SOBP moved distally. Comparison of the residual number of γH2AX foci at the end 24 h after the irradiation revealed, for both cell lines, a higher number of foci in the cells irradiated at the distal end of the SOPB than in those irradiated at the proximal end or center of the SOBP. The results of this study demonstrate that the RBE of a high-energy proton beam and the cellular responses, including the DNA damage repair processes, to high-energy proton beam irradiation, differ according to the position on the SOBP, irrespective of the radiosensitivity levels of the cell lines.

  20. Prompt gamma-ray emission from biological tissues during proton irradiation: a preliminary study.

    PubMed

    Polf, J C; Peterson, S; Ciangaru, G; Gillin, M; Beddar, S

    2009-02-07

    In this paper, we present the results of a preliminary study of secondary 'prompt' gamma-ray emission produced by proton-nuclear interactions within tissue during proton radiotherapy. Monte Carlo simulations were performed for mono-energetic proton beams, ranging from 2.5 MeV to 250 MeV, irradiating elemental and tissue targets. Calculations of the emission spectra from different biological tissues and their elemental components were made. Also, prompt gamma rays emitted during delivery of a clinical proton spread-out Bragg peak (SOBP) in a homogeneous water phantom and a water phantom containing heterogeneous tissue inserts were calculated to study the correlation between prompt gamma-ray production and proton dose delivery. The results show that the prompt gamma-ray spectra differ significantly for each type of tissue studied. The relative intensity of the characteristic gamma rays emitted from a given tissue was shown to be proportional to the concentration of each element in that tissue. A strong correlation was found between the delivered SOBP dose distribution and the characteristic prompt gamma-ray production. Based on these results, we discuss the potential use of prompt gamma-ray emission as a method to verify the accuracy and efficacy of doses delivered with proton radiotherapy.

  1. Using In-Service and Coaching to Increase Teachers' Accurate Use of Research-Based Strategies

    ERIC Educational Resources Information Center

    Kretlow, Allison G.; Cooke, Nancy L.; Wood, Charles L.

    2012-01-01

    Increasing the accurate use of research-based practices in classrooms is a critical issue. Professional development is one of the most practical ways to provide practicing teachers with training related to research-based practices. This study examined the effects of in-service plus follow-up coaching on first grade teachers' accurate delivery of…

  2. Sci—Thur PM: Planning and Delivery — 03: Automated delivery and quality assurance of a modulated electron radiation therapy plan

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

    Connell, T; Papaconstadopoulos, P; Alexander, A

    2014-08-15

    Modulated electron radiation therapy (MERT) offers the potential to improve healthy tissue sparing through increased dose conformity. Challenges remain, however, in accurate beamlet dose calculation, plan optimization, collimation method and delivery accuracy. In this work, we investigate the accuracy and efficiency of an end-to-end MERT plan and automated-delivery workflow for the electron boost portion of a previously treated whole breast irradiation case. Dose calculations were performed using Monte Carlo methods and beam weights were determined using a research-based treatment planning system capable of inverse optimization. The plan was delivered to radiochromic film placed in a water equivalent phantom for verification,more » using an automated motorized tertiary collimator. The automated delivery, which covered 4 electron energies, 196 subfields and 6183 total MU was completed in 25.8 minutes, including 6.2 minutes of beam-on time with the remainder of the delivery time spent on collimator leaf motion and the automated interfacing with the accelerator in service mode. The delivery time could be reduced by 5.3 minutes with minor electron collimator modifications and the beam-on time could be reduced by and estimated factor of 2–3 through redesign of the scattering foils. Comparison of the planned and delivered film dose gave 3%/3 mm gamma pass rates of 62.1, 99.8, 97.8, 98.3, and 98.7 percent for the 9, 12, 16, 20 MeV, and combined energy deliveries respectively. Good results were also seen in the delivery verification performed with a MapCHECK 2 device. The results showed that accurate and efficient MERT delivery is possible with current technologies.« less

  3. Convection-enhanced delivery to the central nervous system.

    PubMed

    Lonser, Russell R; Sarntinoranont, Malisa; Morrison, Paul F; Oldfield, Edward H

    2015-03-01

    Convection-enhanced delivery (CED) is a bulk flow-driven process. Its properties permit direct, homogeneous, targeted perfusion of CNS regions with putative therapeutics while bypassing the blood-brain barrier. Development of surrogate imaging tracers that are co-infused during drug delivery now permit accurate, noninvasive real-time tracking of convective infusate flow in nervous system tissues. The potential advantages of CED in the CNS over other currently available drug delivery techniques, including systemic delivery, intrathecal and/or intraventricular distribution, and polymer implantation, have led to its application in research studies and clinical trials. The authors review the biophysical principles of convective flow and the technology, properties, and clinical applications of convective delivery in the CNS.

  4. The development and verification of a highly accurate collision prediction model for automated noncoplanar plan delivery

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

    Yu, Victoria Y.; Tran, Angelia; Nguyen, Dan

    2015-11-15

    Purpose: Significant dosimetric benefits had been previously demonstrated in highly noncoplanar treatment plans. In this study, the authors developed and verified an individualized collision model for the purpose of delivering highly noncoplanar radiotherapy and tested the feasibility of total delivery automation with Varian TrueBeam developer mode. Methods: A hand-held 3D scanner was used to capture the surfaces of an anthropomorphic phantom and a human subject, which were positioned with a computer-aided design model of a TrueBeam machine to create a detailed virtual geometrical collision model. The collision model included gantry, collimator, and couch motion degrees of freedom. The accuracy ofmore » the 3D scanner was validated by scanning a rigid cubical phantom with known dimensions. The collision model was then validated by generating 300 linear accelerator orientations corresponding to 300 gantry-to-couch and gantry-to-phantom distances, and comparing the corresponding distance measurements to their corresponding models. The linear accelerator orientations reflected uniformly sampled noncoplanar beam angles to the head, lung, and prostate. The distance discrepancies between measurements on the physical and virtual systems were used to estimate treatment-site-specific safety buffer distances with 0.1%, 0.01%, and 0.001% probability of collision between the gantry and couch or phantom. Plans containing 20 noncoplanar beams to the brain, lung, and prostate optimized via an in-house noncoplanar radiotherapy platform were converted into XML script for automated delivery and the entire delivery was recorded and timed to demonstrate the feasibility of automated delivery. Results: The 3D scanner measured the dimension of the 14 cm cubic phantom within 0.5 mm. The maximal absolute discrepancy between machine and model measurements for gantry-to-couch and gantry-to-phantom was 0.95 and 2.97 cm, respectively. The reduced accuracy of gantry-to-phantom measurements

  5. The development and verification of a highly accurate collision prediction model for automated noncoplanar plan delivery.

    PubMed

    Yu, Victoria Y; Tran, Angelia; Nguyen, Dan; Cao, Minsong; Ruan, Dan; Low, Daniel A; Sheng, Ke

    2015-11-01

    Significant dosimetric benefits had been previously demonstrated in highly noncoplanar treatment plans. In this study, the authors developed and verified an individualized collision model for the purpose of delivering highly noncoplanar radiotherapy and tested the feasibility of total delivery automation with Varian TrueBeam developer mode. A hand-held 3D scanner was used to capture the surfaces of an anthropomorphic phantom and a human subject, which were positioned with a computer-aided design model of a TrueBeam machine to create a detailed virtual geometrical collision model. The collision model included gantry, collimator, and couch motion degrees of freedom. The accuracy of the 3D scanner was validated by scanning a rigid cubical phantom with known dimensions. The collision model was then validated by generating 300 linear accelerator orientations corresponding to 300 gantry-to-couch and gantry-to-phantom distances, and comparing the corresponding distance measurements to their corresponding models. The linear accelerator orientations reflected uniformly sampled noncoplanar beam angles to the head, lung, and prostate. The distance discrepancies between measurements on the physical and virtual systems were used to estimate treatment-site-specific safety buffer distances with 0.1%, 0.01%, and 0.001% probability of collision between the gantry and couch or phantom. Plans containing 20 noncoplanar beams to the brain, lung, and prostate optimized via an in-house noncoplanar radiotherapy platform were converted into XML script for automated delivery and the entire delivery was recorded and timed to demonstrate the feasibility of automated delivery. The 3D scanner measured the dimension of the 14 cm cubic phantom within 0.5 mm. The maximal absolute discrepancy between machine and model measurements for gantry-to-couch and gantry-to-phantom was 0.95 and 2.97 cm, respectively. The reduced accuracy of gantry-to-phantom measurements was attributed to phantom setup

  6. The development and verification of a highly accurate collision prediction model for automated noncoplanar plan delivery

    PubMed Central

    Yu, Victoria Y.; Tran, Angelia; Nguyen, Dan; Cao, Minsong; Ruan, Dan; Low, Daniel A.; Sheng, Ke

    2015-01-01

    Purpose: Significant dosimetric benefits had been previously demonstrated in highly noncoplanar treatment plans. In this study, the authors developed and verified an individualized collision model for the purpose of delivering highly noncoplanar radiotherapy and tested the feasibility of total delivery automation with Varian TrueBeam developer mode. Methods: A hand-held 3D scanner was used to capture the surfaces of an anthropomorphic phantom and a human subject, which were positioned with a computer-aided design model of a TrueBeam machine to create a detailed virtual geometrical collision model. The collision model included gantry, collimator, and couch motion degrees of freedom. The accuracy of the 3D scanner was validated by scanning a rigid cubical phantom with known dimensions. The collision model was then validated by generating 300 linear accelerator orientations corresponding to 300 gantry-to-couch and gantry-to-phantom distances, and comparing the corresponding distance measurements to their corresponding models. The linear accelerator orientations reflected uniformly sampled noncoplanar beam angles to the head, lung, and prostate. The distance discrepancies between measurements on the physical and virtual systems were used to estimate treatment-site-specific safety buffer distances with 0.1%, 0.01%, and 0.001% probability of collision between the gantry and couch or phantom. Plans containing 20 noncoplanar beams to the brain, lung, and prostate optimized via an in-house noncoplanar radiotherapy platform were converted into XML script for automated delivery and the entire delivery was recorded and timed to demonstrate the feasibility of automated delivery. Results: The 3D scanner measured the dimension of the 14 cm cubic phantom within 0.5 mm. The maximal absolute discrepancy between machine and model measurements for gantry-to-couch and gantry-to-phantom was 0.95 and 2.97 cm, respectively. The reduced accuracy of gantry-to-phantom measurements was

  7. Characteristics of optically stimulated luminescence dosimeters in the spread-out Bragg peak region of clinical proton beams.

    PubMed

    Kerns, James R; Kry, Stephen F; Sahoo, Narayan

    2012-04-01

    clinical proton beams. To achieve accurate dosimetric readings, corrections to the dosimeter response were applied. Corrections tended to be minimal or broadly consistent. The nanoDot OSLD was found to be an acceptable dosimeter for measurement in the SOBP region for a range of clinical proton beams.

  8. SU-FF-T-668: A Simple Algorithm for Range Modulation Wheel Design in Proton Therapy

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

    Nie, X; Nazaryan, Vahagn; Gueye, Paul

    2009-06-01

    Purpose: To develop a simple algorithm in designing the range modulation wheel to generate a very smooth Spread-Out Bragg peak (SOBP) for proton therapy.Method and Materials: A simple algorithm has been developed to generate the weight factors in corresponding pristine Bragg peaks which composed a smooth SOBP in proton therapy. We used a modified analytical Bragg peak function based on Monte Carol simulation tool-kits of Geant4 as pristine Bragg peaks input in our algorithm. A simple METLAB(R) Quad Program was introduced to optimize the cost function in our algorithm. Results: We found out that the existed analytical function of Braggmore » peak can't directly use as pristine Bragg peak dose-depth profile input file in optimization of the weight factors since this model didn't take into account of the scattering factors introducing from the range shifts in modifying the proton beam energies. We have done Geant4 simulations for proton energy of 63.4 MeV with a 1.08 cm SOBP for variation of pristine Bragg peaks which composed this SOBP and modified the existed analytical Bragg peak functions for their peak heights, ranges of R{sub 0}, and Gaussian energies {sigma}{sub E}. We found out that 19 pristine Bragg peaks are enough to achieve a flatness of 1.5% of SOBP which is the best flatness in the publications. Conclusion: This work develops a simple algorithm to generate the weight factors which is used to design a range modulation wheel to generate a smooth SOBP in protonradiation therapy. We have found out that a medium number of pristine Bragg peaks are enough to generate a SOBP with flatness less than 2%. It is potential to generate data base to store in the treatment plan to produce a clinic acceptable SOBP by using our simple algorithm.« less

  9. Depth Dose Measurement using a Scintillating Fiber Optic Dosimeter for Proton Therapy Beam of the Passive-Scattering Mode Having Range Modulator Wheel

    NASA Astrophysics Data System (ADS)

    Hwang, Ui-Jung; Shin, Dongho; Lee, Se Byeong; Lim, Young Kyung; Jeong, Jong Hwi; Kim, Hak Soo; Kim, Ki Hwan

    2018-05-01

    To apply a scintillating fiber dosimetry system to measure the range of a proton therapy beam, a new method was proposed to correct for the quenching effect on measuring an spread out Bragg peak (SOBP) proton beam whose range is modulated by a range modulator wheel. The scintillating fiber dosimetry system was composed of a plastic scintillating fiber (BCF-12), optical fiber (SH 2001), photo multiplier tube (H7546), and data acquisition system (PXI6221 and SCC68). The proton beam was generated by a cyclotron (Proteus-235) in the National Cancer Center in Korea. It operated in the double-scattering mode and the spread out of the Bragg peak was achieved by a spinning range modulation wheel. Bragg peak beams and SOBP beams of various ranges were measured, corrected, and compared to the ion chamber data. For the Bragg peak beam, quenching equation was used to correct the quenching effect. On the proposed process of correcting SOBP beams, the measured data using a scintillating fiber were separated by the Bragg peaks that the SOBP beam contained, and then recomposed again to reconstruct an SOBP after correcting for each Bragg peak. The measured depth-dose curve for the single Bragg peak beam was well corrected by using a simple quenching equation. Correction for SOBP beam was conducted with a newly proposed method. The corrected SOBP signal was in accordance with the results measured with an ion chamber. We propose a new method to correct for the SOBP beam from the quenching effect in a scintillating fiber dosimetry system. This method can be applied to other scintillator dosimetry for radiation beams in which the quenching effect is shown in the scintillator.

  10. Quality assurance of proton beams using a multilayer ionization chamber system

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

    Dhanesar, Sandeep; Sahoo, Narayan; Kerr, Matthew

    2013-09-15

    Purpose: The measurement of percentage depth-dose (PDD) distributions for the quality assurance of clinical proton beams is most commonly performed with a computerized water tank dosimetry system with ionization chamber, commonly referred to as water tank. Although the accuracy and reproducibility of this method is well established, it can be time-consuming if a large number of measurements are required. In this work the authors evaluate the linearity, reproducibility, sensitivity to field size, accuracy, and time-savings of another system: the Zebra, a multilayer ionization chamber system.Methods: The Zebra, consisting of 180 parallel-plate ionization chambers with 2 mm resolution, was used tomore » measure depth-dose distributions. The measurements were performed for scattered and scanned proton pencil beams of multiple energies delivered by the Hitachi PROBEAT synchrotron-based delivery system. For scattered beams, the Zebra-measured depth-dose distributions were compared with those measured with the water tank. The principal descriptors extracted for comparisons were: range, the depth of the distal 90% dose; spread-out Bragg peak (SOBP) length, the region between the proximal 95% and distal 90% dose; and distal-dose fall off (DDF), the region between the distal 80% and 20% dose. For scanned beams, the Zebra-measured ranges were compared with those acquired using a Bragg peak chamber during commissioning.Results: The Zebra demonstrated better than 1% reproducibility and monitor unit linearity. The response of the Zebra was found to be sensitive to radiation field sizes greater than 12.5 × 12.5 cm; hence, the measurements used to determine accuracy were performed using a field size of 10 × 10 cm. For the scattered proton beams, PDD distributions showed 1.5% agreement within the SOBP, and 3.8% outside. Range values agreed within −0.1 ± 0.4 mm, with a maximum deviation of 1.2 mm. SOBP length values agreed within 0 ± 2 mm, with a maximum deviation of 6 mm

  11. Drug delivery optimization through Bayesian networks.

    PubMed Central

    Bellazzi, R.

    1992-01-01

    This paper describes how Bayesian Networks can be used in combination with compartmental models to plan Recombinant Human Erythropoietin (r-HuEPO) delivery in the treatment of anemia of chronic uremic patients. Past measurements of hematocrit or hemoglobin concentration in a patient during the therapy can be exploited to adjust the parameters of a compartmental model of the erythropoiesis. This adaptive process allows more accurate patient-specific predictions, and hence a more rational dosage planning. We describe a drug delivery optimization protocol, based on our approach. Some results obtained on real data are presented. PMID:1482938

  12. Delivery system for molten salt oxidation of solid waste

    DOEpatents

    Brummond, William A.; Squire, Dwight V.; Robinson, Jeffrey A.; House, Palmer A.

    2002-01-01

    The present invention is a delivery system for safety injecting solid waste particles, including mixed wastes, into a molten salt bath for destruction by the process of molten salt oxidation. The delivery system includes a feeder system and an injector that allow the solid waste stream to be accurately metered, evenly dispersed in the oxidant gas, and maintained at a temperature below incineration temperature while entering the molten salt reactor.

  13. Accurate Treatment of Collision and Water-Delivery in Models of Terrestrial Planet Formation

    NASA Astrophysics Data System (ADS)

    Haghighipour, N.; Maindl, T. I.; Schaefer, C. M.; Wandel, O.

    2017-08-01

    We have developed a comprehensive approach in simulating collisions and growth of embryos to terrestrial planets where we use a combination of SPH and N-body codes to model collisions and the transfer of water and chemical compounds accurately.

  14. LumenRECON Guidewire: Pilot Study of a Novel, Nonimaging Technology for Accurate Vessel Sizing and Delivery of Therapy in Femoropopliteal Disease.

    PubMed

    Nair, Pradeep K; Carr, Jeffrey G; Bigelow, Brian; Bhatt, Deepak L; Berwick, Zachary C; Adams, George

    2018-01-01

    Proper vessel sizing during endovascular interventions is crucial to avoid adverse procedural and clinical outcomes. LumenRECON (LR) is a novel, nonimaging, 0.035-inch wire-based technology that uses the physics-based principle of Ohm's law to provide a simple, real-time luminal size while also providing a platform for therapy delivery. This study evaluated the accuracy, reliability, and safety of the LR system in patients presenting for a femoropopliteal artery intervention. This multicenter, prospective pilot study of 24 patients presenting for peripheral intervention compared LR measurements of femoropopliteal artery size to angiographic visual estimation, duplex ultrasound, quantitative angiography, and intravascular ultrasound. The primary effectiveness and safety end point was comparison against core laboratory adjudicated intravascular ultrasound values and major adverse events, respectively. Additional preclinical studies were also performed in vitro and in vivo in swine to determine the accuracy of the LR guidewire system. No intra- or postprocedure device-related adverse events occurred. A balloon or stent was successfully delivered in 12 patients (50%) over the LR wire. Differences in repeatability between successive LR measurements was 2.5±0.40% ( R 2 =0.96) with no significant bias. Differences in measurements of LR to other modalities were 0.5±1.7%, 5.0±1.8%, -1.5±2.0%, and 6.8±3.4% for intravascular ultrasound core laboratory, quantitative angiography, angiographic, and duplex ultrasound, respectively. This study demonstrates that through a physics-based principle, LR provides a real-time, safe, reproducible, and accurate vessel size of the femoropopliteal artery during intervention and can additionally serve as a conduit for therapy delivery over its wire-based platform. © 2018 American Heart Association, Inc.

  15. 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.

  16. SU-E-T-789: Validation of 3DVH Accuracy On Quantifying Delivery Errors Based On Clinical Relevant DVH Metrics

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

    Ma, T; Kumaraswamy, L

    Purpose: Detection of treatment delivery errors is important in radiation therapy. However, accurate quantification of delivery errors is also of great importance. This study aims to evaluate the 3DVH software’s ability to accurately quantify delivery errors. Methods: Three VMAT plans (prostate, H&N and brain) were randomly chosen for this study. First, we evaluated whether delivery errors could be detected by gamma evaluation. Conventional per-beam IMRT QA was performed with the ArcCHECK diode detector for the original plans and for the following modified plans: (1) induced dose difference error up to ±4.0% and (2) control point (CP) deletion (3 to 10more » CPs were deleted) (3) gantry angle shift error (3 degree uniformly shift). 2D and 3D gamma evaluation were performed for all plans through SNC Patient and 3DVH, respectively. Subsequently, we investigated the accuracy of 3DVH analysis for all cases. This part evaluated, using the Eclipse TPS plans as standard, whether 3DVH accurately can model the changes in clinically relevant metrics caused by the delivery errors. Results: 2D evaluation seemed to be more sensitive to delivery errors. The average differences between ECLIPSE predicted and 3DVH results for each pair of specific DVH constraints were within 2% for all three types of error-induced treatment plans, illustrating the fact that 3DVH is fairly accurate in quantifying the delivery errors. Another interesting observation was that even though the gamma pass rates for the error plans are high, the DVHs showed significant differences between original plan and error-induced plans in both Eclipse and 3DVH analysis. Conclusion: The 3DVH software is shown to accurately quantify the error in delivered dose based on clinically relevant DVH metrics, where a conventional gamma based pre-treatment QA might not necessarily detect.« less

  17. Is measurement of cervical length an accurate predictive tool in women with a history of preterm delivery who present with threatened preterm labor?

    PubMed

    Melamed, N; Hiersch, L; Meizner, I; Bardin, R; Wiznitzer, A; Yogev, Y

    2014-12-01

    To determine whether sonographically measured cervical length is an effective predictive tool in women with threatened preterm labor and a history of past spontaneous preterm delivery. This was a retrospective cohort study of all women with singleton pregnancies who presented with preterm labor at less than 34 + 0 weeks' gestation and underwent sonographic measurement of cervical length in a tertiary medical center between 2007 and 2012. The accuracy of cervical length in predicting preterm delivery was compared between women with and those without a history of spontaneous preterm delivery. Women with risk factors for preterm delivery other than a history of preterm delivery were excluded from both groups. Overall, 1023 women who presented with preterm labor met the study criteria, of whom 136 (13.3%) had a history of preterm delivery (past-PTD group) and 887 (86.7%) had no risk factors for preterm delivery (low-risk group). The rate of preterm delivery was significantly higher for women with a history of preterm delivery (36.8% vs 22.5%; P < 0.001). Cervical length was significantly correlated with the examination-to-delivery interval in low-risk women (r = 0.32, P < 0.001) but not in women who had had a previous preterm delivery (r = 0.07, P = 0.4). On multivariable analysis, cervical length was independently associated with the risk of preterm delivery for women in the low-risk group but not for women with a history of previous preterm delivery. For women with previous preterm delivery who presented with threatened preterm labor, cervical length failed to distinguish between those who did and those who did not deliver prematurely (area under the receiver-operating characteristics curve range, 0.475-0.506). When using standardized thresholds, the sensitivity and specificity of cervical length for the prediction of preterm delivery were significantly lower in women with previous preterm delivery than in women with no risk factors for

  18. Synthetic Tumor Networks for Screening Drug Delivery Systems

    PubMed Central

    Prabhakarpandian, Balabhaskar; Shen, Ming-Che; Nichols, Joseph B.; Garson, Charles J.; Mills, Ivy R.; Matar, Majed M.; Fewell, Jason G.; Pant, Kapil

    2015-01-01

    Tumor drug delivery is a complex phenomenon affected by several elements in addition to drug or delivery vehicle’s physico-chemical properties. A key factor is tumor microvasculature with complex effects including convective transport, high interstitial pressure and enhanced vascular permeability due to the presence of “leaky vessels”. Current in vitro models of the tumor microenvironment for evaluating drug delivery are oversimplified and, as a result, show poor correlation with in vivo performance. In this study, we report on the development of a novel microfluidic platform that models the tumor microenvironment more accurately, with physiologically and morphologically realistic microvasculature including endothelial cell lined leaky capillary vessels along with 3D solid tumors. Endothelial cells and 3D spheroids of cervical tumor cells were co-cultured in the networks. Drug vehicle screening was demonstrated using GFP gene delivery by different formulations of nanopolymers. The synthetic tumor network was successful in predicting in vivo delivery efficiencies of the drug vehicles. The developed assay will have critical applications both in basic research, where it can be used to develop next generation delivery vehicles, and in drug discovery where it can be used to study drug transport and delivery efficacy in realistic tumor microenvironment, thereby enabling drug compound and/or delivery vehicle screening. PMID:25599856

  19. A modified microdosimetric kinetic model for relative biological effectiveness calculation

    NASA Astrophysics Data System (ADS)

    Chen, Yizheng; Li, Junli; Li, Chunyan; Qiu, Rui; Wu, Zhen

    2018-01-01

    constant β value, while a minimal value of β is calculated with the MMKM at this position. Besides, the discrepancy of the averaged cell survival fraction in the SOBP calculated with the two models is more than 15% at the high dose level. The MMKM may provide a reference for the accurate calculation of the RBE value in heavy ion therapy.

  20. Characteristics of optically stimulated luminescence dosimeters in the spread-out Bragg peak region of clinical proton beams

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

    Kerns, James R.; Kry, Stephen F.; Sahoo, Narayan

    characteristics were studied in the SOBP region of clinical proton beams. To achieve accurate dosimetric readings, corrections to the dosimeter response were applied. Corrections tended to be minimal or broadly consistent. The nanoDot OSLD was found to be an acceptable dosimeter for measurement in the SOBP region for a range of clinical proton beams.« less

  1. Assessment of umbilical artery flow and fetal heart rate to predict delivery time in bitches.

    PubMed

    Giannico, Amália Turner; Garcia, Daniela Aparecida Ayres; Gil, Elaine Mayumi Ueno; Sousa, Marlos Gonçalves; Froes, Tilde Rodrigues

    2016-10-15

    The aim of this study was to quantitatively investigate the oscillation of the fetal heart rate (HR) in advance of normal delivery and whether this index could be used to indicate impending delivery. In addition, fetal HR oscillation and umbilical artery resistive index (RI) were correlated to determine if the combination of these parameters provided a more accurate prediction of the time of delivery. Sonographic evaluation was performed in 11 pregnant bitches to evaluate the fetal HR and umbilical artery RI at the following antepartum times: 120 to 96 hours, 72 to 48 hours, 24 to 12 hours, and 12 to 1 hours. Statistical analysis indicated a correlation between the oscillation of fetal HR and the umbilical artery RI. As delivery approached a considerable reduction in the umbilical artery RI was documented and greater oscillations between maximum and minimum HRs occurred. We conclude that the quantitative analysis of fetal HR oscillations may be used to predict the time of delivery in bitches. The combination of fetal HR and umbilical artery RI together may provide more accurate predictions of time of delivery. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Incorporating partial shining effects in proton pencil-beam dose calculation

    NASA Astrophysics Data System (ADS)

    Li, Yupeng; Zhang, Xiaodong; Fwu Lii, Ming; Sahoo, Narayan; Zhu, Ron X.; Gillin, Michael; Mohan, Radhe

    2008-02-01

    A range modulator wheel (RMW) is an essential component in passively scattered proton therapy. We have observed that a proton beam spot may shine on multiple steps of the RMW. Proton dose calculation algorithms normally do not consider the partial shining effect, and thus overestimate the dose at the proximal shoulder of spread-out Bragg peak (SOBP) compared with the measurement. If the SOBP is adjusted to better fit the plateau region, the entrance dose is likely to be underestimated. In this work, we developed an algorithm that can be used to model this effect and to allow for dose calculations that better fit the measured SOBP. First, a set of apparent modulator weights was calculated without considering partial shining. Next, protons spilled from the accelerator reaching the modulator wheel were simplified as a circular spot of uniform intensity. A weight-splitting process was then performed to generate a set of effective modulator weights with the partial shining effect incorporated. The SOBPs of eight options, which are used to label different combinations of proton-beam energy and scattering devices, were calculated with the generated effective weights. Our algorithm fitted the measured SOBP at the proximal and entrance regions much better than the ones without considering partial shining effect for all SOBPs of the eight options. In a prostate patient, we found that dose calculation without considering partial shining effect underestimated the femoral head and skin dose.

  3. Considerations in insulin delivery device selection.

    PubMed

    Valentine, Virginia; Kruger, Davida F

    2010-06-01

    Recent guidelines from the American Diabetes Association and the European Association for the Study of Diabetes promote the use of insulin sooner rather than later in patients with type 2 diabetes to achieve goal range glucose control (< 7%) but remain silent on a recommendation for delivery system. Even though there is widespread consensus among experts and payers that people with type 2 diabetes should use insulin earlier to achieve tight control, it still remains an elusive goal. Benefits of pen-type delivery devices include accurate dosing, faster and easier setting of dose and injection times, and increased patient acceptance and adherence. Before healthcare professionals can recommend a delivery device, it is critical they understand not only the medication in the device but also the various features and benefits to the different devices available and how those impact the patient. We will present considerations to assist in making appropriate device selection, to optimize patient success.

  4. Accuracy and consistency of drop delivery in infusion pumps.

    PubMed

    Yau, K I; Miyasaka, K

    1990-04-01

    Advances in intensive care medicine has made us more depend on infusion pumps to deliver accurate amounts of fluids to sick newborns, children and adults. When infusing rapid-acting critical drugs to patients, it is important not only to deliver accurate fluid-volume amounts over a specified time, but also to deliver the fluid at a constant rate with minimal fluctuation. The accuracy of drop delivery in four infusion pumps (IVAC 530, IVAC 560, IMED 922 and IMED 960) at different infusion rates were examined in a laboratory setting by using a photoelectric sensor and a computer. When it was not in its cassette-filling period, the IMED 960 was the most accurate at delivering fluid-drops, with a coefficient of variance (CV) of less than 10% at each flow rate. Yet, like other piston-cylinder cassette pumps, its cassette filling time and stabilizing period after cassette filling were longer at lower flow rates. Both the IVAC 530 and the IMED 922 delivered fluids irregularly with large coefficients of variance (CVs). IVAC 560 had the best results for consistency of drop-delivery over a 4-hour period.

  5. Time-resolved optically stimulated luminescence of Al2O3:C for ion beam therapy dosimetry

    NASA Astrophysics Data System (ADS)

    Yukihara, Eduardo G.; Doull, Brandon A.; Ahmed, Md; Brons, Stephan; Tessonnier, Thomas; Jäkel, Oliver; Greilich, Steffen

    2015-09-01

    The objective of this study was to characterize the time-resolved (TR) optically stimulated luminescence (OSL) from Al2O3:C detectors and investigate methodologies to improve the accuracy of these detectors in ion beam therapy dosimetry, addressing the reduction in relative response to high linear energy transfer (LET) particles common to solid-state detectors. Al2O3:C OSL detectors (OSLDs) were exposed to proton, 4He, 12C and 16O beams in 22 particle/energy combinations and read using a custom-built TR-OSL reader. The OSL response {{r}\\text{OSL}} , relative to 60Co gamma dose to water, and the ratio between the UV and blue OSL emission bands of Al2O3:C (UV/blue ratio) were determined as a function of the LET. Monte-Carlo simulations with the multi-purpose interaction and transport code FLUKA were used to estimate the absorbed doses and particle energy spectra in the different irradiation conditions. The OSL responses {{r}\\text{OSL}} varied from 0.980 (0.73 keV μm-1) to 0.288 (120.8 keV μm-1). The OSL UV/blue ratio varied by a factor of two in the investigated LET range, but the variation for 12C beams was only 11%. OSLDs were also irradiated at different depths of carbon ion spread-out Bragg peaks (SOBPs), where it was shown that doses could be obtained with an accuracy of  ±2.0% at the entrance channel and within the SOBP using correction factors calculated based on the OSL responses obtained in this study. The UV/blue ratio did not allow accurate estimation of the dose-averaged LET for 12C SOBPs, although the values obtained can be explained with the data obtained in this study and the additional information provided by the Monte-Carlo simulations. The results demonstrate that accurate OSLD dosimetry can be performed in ion beam therapy using appropriate corrections for the OSL response.

  6. An analytical reconstruction model of the spread-out Bragg peak using laser-accelerated proton beams.

    PubMed

    Tao, Li; Zhu, Kun; Zhu, Jungao; Xu, Xiaohan; Lin, Chen; Ma, Wenjun; Lu, Haiyang; Zhao, Yanying; Lu, Yuanrong; Chen, Jia-Er; Yan, Xueqing

    2017-07-07

    With the development of laser technology, laser-driven proton acceleration provides a new method for proton tumor therapy. However, it has not been applied in practice because of the wide and decreasing energy spectrum of laser-accelerated proton beams. In this paper, we propose an analytical model to reconstruct the spread-out Bragg peak (SOBP) using laser-accelerated proton beams. Firstly, we present a modified weighting formula for protons of different energies. Secondly, a theoretical model for the reconstruction of SOBPs with laser-accelerated proton beams has been built. It can quickly calculate the number of laser shots needed for each energy interval of the laser-accelerated protons. Finally, we show the 2D reconstruction results of SOBPs for laser-accelerated proton beams and the ideal situation. The final results show that our analytical model can give an SOBP reconstruction scheme that can be used for actual tumor therapy.

  7. Therapeutic applications of hydrogels in oral drug delivery

    PubMed Central

    Sharpe, Lindsey A; Daily, Adam M; Horava, Sarena D; Peppas, Nicholas A

    2015-01-01

    Introduction Oral delivery of therapeutics, particularly protein-based pharmaceutics, is of great interest for safe and controlled drug delivery for patients. Hydrogels offer excellent potential as oral therapeutic systems due to inherent biocompatibility, diversity of both natural and synthetic material options and tunable properties. In particular, stimuli-responsive hydrogels exploit physiological changes along the intestinal tract to achieve site-specific, controlled release of protein, peptide and chemotherapeutic molecules for both local and systemic treatment applications. Areas covered This review provides a wide perspective on the therapeutic use of hydrogels in oral delivery systems. General features and advantages of hydrogels are addressed, with more considerable focus on stimuli-responsive systems that respond to pH or enzymatic changes in the gastrointestinal environment to achieve controlled drug release. Specific examples of therapeutics are given. Last, in vitro and in vivo methods to evaluate hydrogel performance are discussed. Expert opinion Hydrogels are excellent candidates for oral drug delivery, due to the number of adaptable parameters that enable controlled delivery of diverse therapeutic molecules. However, further work is required to more accurately simulate physiological conditions and enhance performance, which is important to achieve improved bioavailability and increase commercial interest. PMID:24848309

  8. Delivery of Cancer Therapeutics Using Nanotechnology

    PubMed Central

    Lim, Eun-Kyung; Jang, Eunji; Lee, Kwangyeol; Haam, Seungjoo; Huh, Yong-Min

    2013-01-01

    Nanoparticles have been investigated as drug carriers, because they provide a great opportunity due to their advantageous features: (i) various formulations using organic/inorganic materials, (ii) easy modification of targeting molecules, drugs or other molecules on them, (iii) effective delivery to target sites, resulting in high therapeutic efficacy and (iv) controlling drug release by external/internal stimuli. Because of these features, therapeutic efficacy can be improved and unwanted side effects can be reduced. Theranostic nanoparticles have been developed by incorporating imaging agents in drug carriers as all-in-one system, which makes it possible to diagnose and treat cancer by monitoring drug delivery behavior simultaneously. Recently, stimuli-responsive, activatable nanomaterials are being applied that are capable of producing chemical or physical changes by external stimuli. By using these nanoparticles, multiple tasks can be carried out simultaneously, e.g., early and accurate diagnosis, efficient cataloguing of patient groups of personalized therapy and real-time monitoring of disease progress. In this paper, we describe various types of nanoparticles for drug delivery systems, as well as theranostic systems. PMID:24300452

  9. Convection-enhanced Delivery of Therapeutics for Malignant Gliomas.

    PubMed

    Saito, Ryuta; Tominaga, Teiji

    2017-01-15

    Convection-enhanced delivery (CED) circumvents the blood-brain barrier by delivering agents directly into the tumor and surrounding parenchyma. CED can achieve large volumes of distribution by continuous positive-pressure infusion. Although promising as an effective drug delivery method in concept, the administration of therapeutic agents via CED is not without challenges. Limitations of distribution remain a problem in large brains, such as those of humans. Accurate and consistent delivery of an agent is another challenge associated with CED. Similar to the difficulties caused by immunosuppressive environments associated with gliomas, there are several mechanisms that make effective local drug distribution difficult in malignant gliomas. In this review, methods for local drug application targeting gliomas are discussed with special emphasis on CED. Although early clinical trials have failed to demonstrate the efficacy of CED against gliomas, CED potentially can be a platform for translating the molecular understanding of glioblastomas achieved in the laboratory into effective clinical treatments. Several clinical studies using CED of chemotherapeutic agents are ongoing. Successful delivery of effective agents should prove the efficacy of CED in the near future.

  10. Convection-enhanced Delivery of Therapeutics for Malignant Gliomas

    PubMed Central

    SAITO, Ryuta; TOMINAGA, Teiji

    2017-01-01

    Convection-enhanced delivery (CED) circumvents the blood–brain barrier by delivering agents directly into the tumor and surrounding parenchyma. CED can achieve large volumes of distribution by continuous positive-pressure infusion. Although promising as an effective drug delivery method in concept, the administration of therapeutic agents via CED is not without challenges. Limitations of distribution remain a problem in large brains, such as those of humans. Accurate and consistent delivery of an agent is another challenge associated with CED. Similar to the difficulties caused by immunosuppressive environments associated with gliomas, there are several mechanisms that make effective local drug distribution difficult in malignant gliomas. In this review, methods for local drug application targeting gliomas are discussed with special emphasis on CED. Although early clinical trials have failed to demonstrate the efficacy of CED against gliomas, CED potentially can be a platform for translating the molecular understanding of glioblastomas achieved in the laboratory into effective clinical treatments. Several clinical studies using CED of chemotherapeutic agents are ongoing. Successful delivery of effective agents should prove the efficacy of CED in the near future. PMID:27980285

  11. Microencapsulation: A promising technique for controlled drug delivery.

    PubMed

    Singh, M N; Hemant, K S Y; Ram, M; Shivakumar, H G

    2010-07-01

    MICROPARTICLES OFFER VARIOUS SIGNIFICANT ADVANTAGES AS DRUG DELIVERY SYSTEMS, INCLUDING: (i) an effective protection of the encapsulated active agent against (e.g. enzymatic) degradation, (ii) the possibility to accurately control the release rate of the incorporated drug over periods of hours to months, (iii) an easy administration (compared to alternative parenteral controlled release dosage forms, such as macro-sized implants), and (iv) Desired, pre-programmed drug release profiles can be provided which match the therapeutic needs of the patient. This article gives an overview on the general aspects and recent advances in drug-loaded microparticles to improve the efficiency of various medical treatments. An appropriately designed controlled release drug delivery system can be a foot ahead towards solving problems concerning to the targeting of drug to a specific organ or tissue, and controlling the rate of drug delivery to the target site. The development of oral controlled release systems has been a challenge to formulation scientist due to their inability to restrain and localize the system at targeted areas of gastrointestinal tract. Microparticulate drug delivery systems are an interesting and promising option when developing an oral controlled release system. The objective of this paper is to take a closer look at microparticles as drug delivery devices for increasing efficiency of drug delivery, improving the release profile and drug targeting. In order to appreciate the application possibilities of microcapsules in drug delivery, some fundamental aspects are briefly reviewed.

  12. Microencapsulation: A promising technique for controlled drug delivery

    PubMed Central

    Singh, M.N.; Hemant, K.S.Y.; Ram, M.; Shivakumar, H.G.

    2010-01-01

    Microparticles offer various significant advantages as drug delivery systems, including: (i) an effective protection of the encapsulated active agent against (e.g. enzymatic) degradation, (ii) the possibility to accurately control the release rate of the incorporated drug over periods of hours to months, (iii) an easy administration (compared to alternative parenteral controlled release dosage forms, such as macro-sized implants), and (iv) Desired, pre-programmed drug release profiles can be provided which match the therapeutic needs of the patient. This article gives an overview on the general aspects and recent advances in drug-loaded microparticles to improve the efficiency of various medical treatments. An appropriately designed controlled release drug delivery system can be a foot ahead towards solving problems concerning to the targeting of drug to a specific organ or tissue, and controlling the rate of drug delivery to the target site. The development of oral controlled release systems has been a challenge to formulation scientist due to their inability to restrain and localize the system at targeted areas of gastrointestinal tract. Microparticulate drug delivery systems are an interesting and promising option when developing an oral controlled release system. The objective of this paper is to take a closer look at microparticles as drug delivery devices for increasing efficiency of drug delivery, improving the release profile and drug targeting. In order to appreciate the application possibilities of microcapsules in drug delivery, some fundamental aspects are briefly reviewed. PMID:21589795

  13. Commissioning dose computation models for spot scanning proton beams in water for a commercially available treatment planning system

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

    Zhu, X. R.; Poenisch, F.; Lii, M.

    2013-04-15

    Purpose: To present our method and experience in commissioning dose models in water for spot scanning proton therapy in a commercial treatment planning system (TPS). Methods: The input data required by the TPS included in-air transverse profiles and integral depth doses (IDDs). All input data were obtained from Monte Carlo (MC) simulations that had been validated by measurements. MC-generated IDDs were converted to units of Gy mm{sup 2}/MU using the measured IDDs at a depth of 2 cm employing the largest commercially available parallel-plate ionization chamber. The sensitive area of the chamber was insufficient to fully encompass the entire lateralmore » dose deposited at depth by a pencil beam (spot). To correct for the detector size, correction factors as a function of proton energy were defined and determined using MC. The fluence of individual spots was initially modeled as a single Gaussian (SG) function and later as a double Gaussian (DG) function. The DG fluence model was introduced to account for the spot fluence due to contributions of large angle scattering from the devices within the scanning nozzle, especially from the spot profile monitor. To validate the DG fluence model, we compared calculations and measurements, including doses at the center of spread out Bragg peaks (SOBPs) as a function of nominal field size, range, and SOBP width, lateral dose profiles, and depth doses for different widths of SOBP. Dose models were validated extensively with patient treatment field-specific measurements. Results: We demonstrated that the DG fluence model is necessary for predicting the field size dependence of dose distributions. With this model, the calculated doses at the center of SOBPs as a function of nominal field size, range, and SOBP width, lateral dose profiles and depth doses for rectangular target volumes agreed well with respective measured values. With the DG fluence model for our scanning proton beam line, we successfully treated more than 500

  14. Commissioning dose computation models for spot scanning proton beams in water for a commercially available treatment planning system

    PubMed Central

    Zhu, X. R.; Poenisch, F.; Lii, M.; Sawakuchi, G. O.; Titt, U.; Bues, M.; Song, X.; Zhang, X.; Li, Y.; Ciangaru, G.; Li, H.; Taylor, M. B.; Suzuki, K.; Mohan, R.; Gillin, M. T.; Sahoo, N.

    2013-01-01

    Purpose: To present our method and experience in commissioning dose models in water for spot scanning proton therapy in a commercial treatment planning system (TPS). Methods: The input data required by the TPS included in-air transverse profiles and integral depth doses (IDDs). All input data were obtained from Monte Carlo (MC) simulations that had been validated by measurements. MC-generated IDDs were converted to units of Gy mm2/MU using the measured IDDs at a depth of 2 cm employing the largest commercially available parallel-plate ionization chamber. The sensitive area of the chamber was insufficient to fully encompass the entire lateral dose deposited at depth by a pencil beam (spot). To correct for the detector size, correction factors as a function of proton energy were defined and determined using MC. The fluence of individual spots was initially modeled as a single Gaussian (SG) function and later as a double Gaussian (DG) function. The DG fluence model was introduced to account for the spot fluence due to contributions of large angle scattering from the devices within the scanning nozzle, especially from the spot profile monitor. To validate the DG fluence model, we compared calculations and measurements, including doses at the center of spread out Bragg peaks (SOBPs) as a function of nominal field size, range, and SOBP width, lateral dose profiles, and depth doses for different widths of SOBP. Dose models were validated extensively with patient treatment field-specific measurements. Results: We demonstrated that the DG fluence model is necessary for predicting the field size dependence of dose distributions. With this model, the calculated doses at the center of SOBPs as a function of nominal field size, range, and SOBP width, lateral dose profiles and depth doses for rectangular target volumes agreed well with respective measured values. With the DG fluence model for our scanning proton beam line, we successfully treated more than 500 patients from

  15. Commissioning dose computation models for spot scanning proton beams in water for a commercially available treatment planning system.

    PubMed

    Zhu, X R; Poenisch, F; Lii, M; Sawakuchi, G O; Titt, U; Bues, M; Song, X; Zhang, X; Li, Y; Ciangaru, G; Li, H; Taylor, M B; Suzuki, K; Mohan, R; Gillin, M T; Sahoo, N

    2013-04-01

    To present our method and experience in commissioning dose models in water for spot scanning proton therapy in a commercial treatment planning system (TPS). The input data required by the TPS included in-air transverse profiles and integral depth doses (IDDs). All input data were obtained from Monte Carlo (MC) simulations that had been validated by measurements. MC-generated IDDs were converted to units of Gy mm(2)/MU using the measured IDDs at a depth of 2 cm employing the largest commercially available parallel-plate ionization chamber. The sensitive area of the chamber was insufficient to fully encompass the entire lateral dose deposited at depth by a pencil beam (spot). To correct for the detector size, correction factors as a function of proton energy were defined and determined using MC. The fluence of individual spots was initially modeled as a single Gaussian (SG) function and later as a double Gaussian (DG) function. The DG fluence model was introduced to account for the spot fluence due to contributions of large angle scattering from the devices within the scanning nozzle, especially from the spot profile monitor. To validate the DG fluence model, we compared calculations and measurements, including doses at the center of spread out Bragg peaks (SOBPs) as a function of nominal field size, range, and SOBP width, lateral dose profiles, and depth doses for different widths of SOBP. Dose models were validated extensively with patient treatment field-specific measurements. We demonstrated that the DG fluence model is necessary for predicting the field size dependence of dose distributions. With this model, the calculated doses at the center of SOBPs as a function of nominal field size, range, and SOBP width, lateral dose profiles and depth doses for rectangular target volumes agreed well with respective measured values. With the DG fluence model for our scanning proton beam line, we successfully treated more than 500 patients from March 2010 through June 2012

  16. SU-E-T-649: Quality Assurances for Proton Therapy Delivery Equipment

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

    Arjomandy, B; Kase, Y; Flanz, J

    2015-06-15

    Purpose: The number of proton therapy centers has increased dramatically over the past decade. Currently, there is no comprehensive set of guidelines that addresses quality assurance (QA) procedures for the different technologies used for proton therapy. The AAPM has charged task group 224 (TG-224) to provide recommendations for QA required for accurate and safe dose delivery, using existing and next generation proton therapy delivery equipment. Methods: A database comprised of QA procedures and tolerance limits was generated from many existing proton therapy centers in and outside of the US. These consist of proton therapy centers that possessed double scattering, uniformmore » scanning, and pencil beams delivery systems. The diversity in beam delivery systems as well as the existing devices to perform QA checks for different beam parameters is the main subject of TG-224. Based on current practice at the clinically active proton centers participating in this task group, consensus QA recommendations were developed. The methodologies and requirements of the parameters that must be verified for consistency of the performance of the proton beam delivery systems are discussed. Results: TG-224 provides procedures and QA checks for mechanical, imaging, safety and dosimetry requirements for different proton equipment. These procedures are categorized based on their importance and their required frequencies in order to deliver a safe and consistent dose. The task group provides daily, weekly, monthly, and annual QA check procedures with their tolerance limits. Conclusions: The procedures outlined in this protocol provide sufficient information to qualified medical physicists to perform QA checks for any proton delivery system. Execution of these procedures should provide confidence that proton therapy equipment is functioning as commissioned for patient treatment and delivers dose safely and accurately within the established tolerance limits. The report will be published

  17. A convenient and accurate parallel Input/Output USB device for E-Prime.

    PubMed

    Canto, Rosario; Bufalari, Ilaria; D'Ausilio, Alessandro

    2011-03-01

    Psychological and neurophysiological experiments require the accurate control of timing and synchrony for Input/Output signals. For instance, a typical Event-Related Potential (ERP) study requires an extremely accurate synchronization of stimulus delivery with recordings. This is typically done via computer software such as E-Prime, and fast communications are typically assured by the Parallel Port (PP). However, the PP is an old and disappearing technology that, for example, is no longer available on portable computers. Here we propose a convenient USB device enabling parallel I/O capabilities. We tested this device against the PP on both a desktop and a laptop machine in different stress tests. Our data demonstrate the accuracy of our system, which suggests that it may be a good substitute for the PP with E-Prime.

  18. Revolutionary Impact of Nanodrug Delivery on Neuroscience

    PubMed Central

    Khanbabaie, Reza; Jahanshahi, Mohsen

    2012-01-01

    Brain research is the most expanding interdisciplinary research that is using the state of the art techniques to overcome limitations in order to conduct more accurate and effective experiments. Drug delivery to the target site in the central nervous system (CNS) is one of the most difficult steps in neuroscience researches and therapies. Taking advantage of the nanoscale structure of neural cells (both neurons and glia); nanodrug delivery (second generation of biotechnological products) has a potential revolutionary impact into the basic understanding, visualization and therapeutic applications of neuroscience. Current review article firstly provides an overview of preparation and characterization, purification and separation, loading and delivering of nanodrugs. Different types of nanoparticle bioproducts and a number of methods for their fabrication and delivery systems including (carbon) nanotubes are explained. In the second part, neuroscience and nervous system drugs are deeply investigated. Different mechanisms in which nanoparticles enhance the uptake and clearance of molecules form cerebrospinal fluid (CSF) are discussed. The focus is on nanodrugs that are being used or have potential to improve neural researches, diagnosis and therapy of neurodegenerative disorders. PMID:23730260

  19. Relative biological effectiveness (RBE) and distal edge effects of proton radiation on early damage in vivo.

    PubMed

    Sørensen, Brita Singers; Bassler, Niels; Nielsen, Steffen; Horsman, Michael R; Grzanka, Leszek; Spejlborg, Harald; Swakoń, Jan; Olko, Paweł; Overgaard, Jens

    2017-11-01

    The aim of the present study was to examine the RBE for early damage in an in vivo mouse model, and the effect of the increased linear energy transfer (LET) towards the distal edge of the spread-out Bragg peak (SOBP). The lower part of the right hind limb of CDF1 mice was irradiated with single fractions of either 6 MV photons, 240 kV photons or scanning beam protons and graded doses were applied. For the proton irradiation, the leg was either placed in the middle of a 30-mm SOBP, or to assess the effect in different positions, irradiated in 4 mm intervals from the middle of the SOBP to behind the distal dose fall-off. Irradiations were performed with the same dose plan at all positions, corresponding to a dose of 31.25 Gy in the middle of the SOBP. Endpoint of the study was early skin damage of the foot, assessed by a mouse foot skin scoring system. The MDD 50 values with 95% confidence intervals were 36.1 (34.2-38.1) Gy for protons in the middle of the SOBP for score 3.5. For 6 MV photons, it was 35.9 (34.5-37.5) Gy and 32.6 (30.7-34.7) Gy for 240 kV photons for score 3.5. The corresponding RBE was 1.00 (0.94-1.05), relative to 6 MV photons and 0.9 (0.85-0.97) relative to 240 kV photons. In the mice group positioned at the SOBP distal dose fall-off, 25% of the mice developed early skin damage compared with 0-8% in other groups. LET d,z = 1 was 8.4 keV/μm at the distal dose fall-off and the physical dose delivered was 7% lower than in the central SOBP position, where LET d,z =1 was 3.3 keV/μm. Although there is a need to expand the current study to be able to calculate an exact enhancement ratio, an enhanced biological effect in vivo for early skin damage in the distal edge was demonstrated.

  20. 4D dose calculation and delivery with interplay effects between respiratory motion and uniform scanning proton beam

    NASA Astrophysics Data System (ADS)

    Zhao, Qingya

    2011-12-01

    Proton radiotherapy has advantages to deliver accurate high conformal radiation dose to the tumor while sparing the surrounding healthy tissue and critical structures. However, the treatment effectiveness is degraded greatly due to patient free breathing during treatment delivery. Motion compensation for proton radiotherapy is especially challenging as proton beam is more sensitive to the density change along the beam path. Tumor respiratory motion during treatment delivery will affect the proton dose distribution and the selection of optimized parameters for treatment planning, which has not been fully addressed yet in the existing approaches for proton dose calculation. The purpose of this dissertation is to develop an approach for more accurate dose delivery to a moving tumor in proton radiotherapy, i.e., 4D proton dose calculation and delivery, for the uniform scanning proton beam. A three-step approach has been carried out to achieve this goal. First, a solution for the proton output factor calculation which will convert the prescribed dose to machine deliverable monitor unit for proton dose delivery has been proposed and implemented. The novel sector integration method is accurate and time saving, which considers the various beam scanning patterns and treatment field parameters, such as aperture shape, aperture size, measuring position, beam range, and beam modulation. Second, tumor respiratory motion behavior has been statistically characterized and the results have been applied to advanced image guided radiation treatment. Different statistical analysis and correlation discovery approaches have been investigated. The internal / external motion correlation patterns have been simulated, analyzed, and applied in a new hybrid gated treatment to improve the target coverage. Third, a dose calculation method has been developed for 4D proton treatment planning which integrates the interplay effects of tumor respiratory motion patterns and proton beam delivery

  1. Exploration of the Performance of a Hybrid Closed Loop Insulin Delivery Algorithm That Includes Insulin Delivery Limits Designed to Protect Against Hypoglycemia.

    PubMed

    de Bock, Martin; Dart, Julie; Roy, Anirban; Davey, Raymond; Soon, Wayne; Berthold, Carolyn; Retterath, Adam; Grosman, Benyamin; Kurtz, Natalie; Davis, Elizabeth; Jones, Timothy

    2017-01-01

    Hypoglycemia remains a risk for closed loop insulin delivery particularly following exercise or if the glucose sensor is inaccurate. The aim of this study was to test whether an algorithm that includes a limit to insulin delivery is effective at protecting against hypoglycemia under those circumstances. An observational study on 8 participants with type 1 diabetes was conducted, where a hybrid closed loop system (HCL) (Medtronic™ 670G) was challenged with hypoglycemic stimuli: exercise and an overreading glucose sensor. There was no overnight or exercise-induced hypoglycemia during HCL insulin delivery. All daytime hypoglycemia was attributable to postmeal bolused insulin in those participants with a more aggressive carbohydrate factor. HCL systems rely on accurate carbohydrate ratios and carbohydrate counting to avoid hypoglycemia. The algorithm that was tested against moderate exercise and an overreading glucose sensor performed well in terms of hypoglycemia avoidance. Algorithm refinement continues in preparation for long-term outpatient trials.

  2. Dosimetric evaluation of a commercial proton spot scanning Monte-Carlo dose algorithm: comparisons against measurements and simulations

    NASA Astrophysics Data System (ADS)

    Saini, Jatinder; Maes, Dominic; Egan, Alexander; Bowen, Stephen R.; St. James, Sara; Janson, Martin; Wong, Tony; Bloch, Charles

    2017-10-01

    RaySearch Americas Inc. (NY) has introduced a commercial Monte Carlo dose algorithm (RS-MC) for routine clinical use in proton spot scanning. In this report, we provide a validation of this algorithm against phantom measurements and simulations in the GATE software package. We also compared the performance of the RayStation analytical algorithm (RS-PBA) against the RS-MC algorithm. A beam model (G-MC) for a spot scanning gantry at our proton center was implemented in the GATE software package. The model was validated against measurements in a water phantom and was used for benchmarking the RS-MC. Validation of the RS-MC was performed in a water phantom by measuring depth doses and profiles for three spread-out Bragg peak (SOBP) beams with normal incidence, an SOBP with oblique incidence, and an SOBP with a range shifter and large air gap. The RS-MC was also validated against measurements and simulations in heterogeneous phantoms created by placing lung or bone slabs in a water phantom. Lateral dose profiles near the distal end of the beam were measured with a microDiamond detector and compared to the G-MC simulations, RS-MC and RS-PBA. Finally, the RS-MC and RS-PBA were validated against measured dose distributions in an Alderson-Rando (AR) phantom. Measurements were made using Gafchromic film in the AR phantom and compared to doses using the RS-PBA and RS-MC algorithms. For SOBP depth doses in a water phantom, all three algorithms matched the measurements to within  ±3% at all points and a range within 1 mm. The RS-PBA algorithm showed up to a 10% difference in dose at the entrance for the beam with a range shifter and  >30 cm air gap, while the RS-MC and G-MC were always within 3% of the measurement. For an oblique beam incident at 45°, the RS-PBA algorithm showed up to 6% local dose differences and broadening of distal fall-off by 5 mm. Both the RS-MC and G-MC accurately predicted the depth dose to within  ±3% and distal fall-off to within 2

  3. Dosimetric evaluation of a commercial proton spot scanning Monte-Carlo dose algorithm: comparisons against measurements and simulations.

    PubMed

    Saini, Jatinder; Maes, Dominic; Egan, Alexander; Bowen, Stephen R; St James, Sara; Janson, Martin; Wong, Tony; Bloch, Charles

    2017-09-12

    RaySearch Americas Inc. (NY) has introduced a commercial Monte Carlo dose algorithm (RS-MC) for routine clinical use in proton spot scanning. In this report, we provide a validation of this algorithm against phantom measurements and simulations in the GATE software package. We also compared the performance of the RayStation analytical algorithm (RS-PBA) against the RS-MC algorithm. A beam model (G-MC) for a spot scanning gantry at our proton center was implemented in the GATE software package. The model was validated against measurements in a water phantom and was used for benchmarking the RS-MC. Validation of the RS-MC was performed in a water phantom by measuring depth doses and profiles for three spread-out Bragg peak (SOBP) beams with normal incidence, an SOBP with oblique incidence, and an SOBP with a range shifter and large air gap. The RS-MC was also validated against measurements and simulations in heterogeneous phantoms created by placing lung or bone slabs in a water phantom. Lateral dose profiles near the distal end of the beam were measured with a microDiamond detector and compared to the G-MC simulations, RS-MC and RS-PBA. Finally, the RS-MC and RS-PBA were validated against measured dose distributions in an Alderson-Rando (AR) phantom. Measurements were made using Gafchromic film in the AR phantom and compared to doses using the RS-PBA and RS-MC algorithms. For SOBP depth doses in a water phantom, all three algorithms matched the measurements to within  ±3% at all points and a range within 1 mm. The RS-PBA algorithm showed up to a 10% difference in dose at the entrance for the beam with a range shifter and  >30 cm air gap, while the RS-MC and G-MC were always within 3% of the measurement. For an oblique beam incident at 45°, the RS-PBA algorithm showed up to 6% local dose differences and broadening of distal fall-off by 5 mm. Both the RS-MC and G-MC accurately predicted the depth dose to within  ±3% and distal fall-off to within 2

  4. Characterization of a multilayer ionization chamber prototype for fast verification of relative depth ionization curves and spread-out-Bragg-peaks in light ion beam therapy.

    PubMed

    Mirandola, Alfredo; Magro, Giuseppe; Lavagno, Marco; Mairani, Andrea; Molinelli, Silvia; Russo, Stefania; Mastella, Edoardo; Vai, Alessandro; Maestri, Davide; La Rosa, Vanessa; Ciocca, Mario

    2018-05-01

    to 0.7% (1.9%) for the 50% (20%) beam flux level. The short-term stability of the gain calibration was very satisfying for both particle types: the channel mean relative standard deviation was within ±1% for all the acquisitions performed at different times. The ICs obtained with the MLIC QUBE at improved resolution satisfactorily matched both the MC simulations and the reference curves acquired with Peakfinder. Deviations from the reference values in terms of BP position, peak width and distal fall-off were submillimetric for both particle types in the whole investigated energy range. For modulated SOBPs, a submillimetric deviation was found when comparing both experimental MLIC QUBE data against the reference values and MC calculations. The relative dose deviations for the experimental MLIC QUBE acquisitions, with respect to Peakfinder data, ranged from ~1% to ~3.5%. Maximum value of 14.1 μSv/h was measured in contact with QUBE entrance window soon after a long irradiation with carbon ions. MLIC QUBE appears to be a promising detector for accurately measuring pristine ICs and SOBPs. A simple procedure to improve the intrinsic spatial resolution of the detector is proposed. Being the detector very accurate, precise, fast responding, and easy to handle, it is therefore well suited for daily checks in PT. © 2018 American Association of Physicists in Medicine.

  5. An Accurate Full-flexion Anterolateral Portal for Needle Placement in the Knee Joint With Dry Osteoarthritis.

    PubMed

    Hussein, Mohamed

    2017-07-01

    Accurate delivery of an injection into the intra-articular space of the knee is achieved in only two thirds of knees when using the standard anterolateral portal. The use of a modified full-flexion anterolateral portal provides a highly accurate, less painful, and more effective method for reproducible intra-articular injection without the need for ultrasonographic or fluoroscopic guidance in patients with dry osteoarthritis of the knee. The accuracy of needle placement was assessed in a prospective series of 140 consecutive injections in patients with symptomatic degenerative knee arthritis without clinical knee effusion. Procedural pain was determined using the Numerical Rating Scale. The accuracy rates of needle placement were confirmed with fluoroscopic imaging to document the dispersion pattern of injected contrast material. Using the standard anterolateral portal, 52 of 70 injections were confirmed to have been placed in the intra-articular space on the first attempt (accuracy rate, 74.2%). Using the modified full-flexion anterolateral portal, 68 of 70 injections were placed in the intra-articular space on the first attempt (accuracy rate, 97.1%; P = 0.000). This study revealed that using the modified full-flexion anterolateral portal for injections into the knee joint resulted in more accurate and less painful injections than those performed by the same orthopaedic surgeon using the standard anterolateral portal. In addition, the technique offered therapeutic delivery into the joint without the need for fluoroscopic confirmation. Therapeutic Level II.

  6. The macrophage as a Trojan horse for antisense oligonucleotide delivery.

    PubMed

    Novak, James S; Jaiswal, Jyoti K; Partridge, Terence A

    2018-06-04

    The gateway to the promised land of gene therapy has been obstructed by the problem of accurate and efficient delivery of therapeutic agents to their target sites. This is true both of constructs designed to directly express proteins of interest, and of constructs or agents aimed at modifying the expression of endogenous genes. It is recognized as a major impediment to the effective application of genetic therapies currently or incipiently in clinical trial. Our recent study has examined the mechanism underlying delivery of therapeutic antisense oligonucleotides (ASO) for treating the devastating muscle disease Duchenne muscular dystrophy [1]. Working to understand the mode of ASO delivery in DMD, we discovered that inflammatory cells act as a depot that locally stores the intravenously administered ASO. This local depot of ASO then becomes available to the muscle fibres by way of satellite cells that deliver their cargo by fusion with damaged fibres during muscle repair. This finding points to a potentially novel strategy for systemic ASO delivery, involving the use of the inflammatory cell as a Trojan horse. Such an approach would have the benefit not only of enhancing tissue-specific delivery of ASO, but also of reducing the impact of their rapid clearance from the circulation. Here, we discuss the issues surrounding ASO-mediated exon skipping efficacy for DMD, and outline research aimed at improving targeted ASO delivery.

  7. Quality Control of High-Dose-Rate Brachytherapy: Treatment Delivery Analysis Using Statistical Process Control

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

    Able, Charles M., E-mail: cable@wfubmc.edu; Bright, Megan; Frizzell, Bart

    Purpose: Statistical process control (SPC) is a quality control method used to ensure that a process is well controlled and operates with little variation. This study determined whether SPC was a viable technique for evaluating the proper operation of a high-dose-rate (HDR) brachytherapy treatment delivery system. Methods and Materials: A surrogate prostate patient was developed using Vyse ordnance gelatin. A total of 10 metal oxide semiconductor field-effect transistors (MOSFETs) were placed from prostate base to apex. Computed tomography guidance was used to accurately position the first detector in each train at the base. The plan consisted of 12 needles withmore » 129 dwell positions delivering a prescribed peripheral dose of 200 cGy. Sixteen accurate treatment trials were delivered as planned. Subsequently, a number of treatments were delivered with errors introduced, including wrong patient, wrong source calibration, wrong connection sequence, single needle displaced inferiorly 5 mm, and entire implant displaced 2 mm and 4 mm inferiorly. Two process behavior charts (PBC), an individual and a moving range chart, were developed for each dosimeter location. Results: There were 4 false positives resulting from 160 measurements from 16 accurately delivered treatments. For the inaccurately delivered treatments, the PBC indicated that measurements made at the periphery and apex (regions of high-dose gradient) were much more sensitive to treatment delivery errors. All errors introduced were correctly identified by either the individual or the moving range PBC in the apex region. Measurements at the urethra and base were less sensitive to errors. Conclusions: SPC is a viable method for assessing the quality of HDR treatment delivery. Further development is necessary to determine the most effective dose sampling, to ensure reproducible evaluation of treatment delivery accuracy.« less

  8. Luminescence imaging of water during uniform-field irradiation by spot scanning proton beams

    NASA Astrophysics Data System (ADS)

    Komori, Masataka; Sekihara, Eri; Yabe, Takuya; Horita, Ryo; Toshito, Toshiyuki; Yamamoto, Seiichi

    2018-06-01

    Luminescence was found during pencil-beam proton irradiation to water phantom and range could be estimated from the luminescence images. However, it is not yet clear whether the luminescence imaging is applied to the uniform fields made of spot-scanning proton-beam irradiations. For this purpose, imaging was conducted for the uniform fields having spread out Bragg peak (SOBP) made by spot scanning proton beams. We designed six types of the uniform fields with different ranges, SOBP widths and irradiation fields. One of the designed fields was irradiated to water phantom and a cooled charge coupled device camera was used to measure the luminescence image during irradiations. We estimated the ranges, field widths, and luminescence intensities from the luminescence images and compared those with the dose distribution calculated by a treatment planning system. For all types of uniform fields, we could obtain clear images of the luminescence showing the SOBPs. The ranges and field widths evaluated from the luminescence were consistent with those of the dose distribution calculated by a treatment planning system within the differences of  ‑4 mm and  ‑11 mm, respectively. Luminescence intensities were almost proportional to the SOBP widths perpendicular to the beam direction. The luminescence imaging could be applied to uniform fields made of spot scanning proton beam irradiations. Ranges and widths of the uniform fields with SOBP could be estimated from the images. The luminescence imaging is promising for the range and field width estimations in proton therapy.

  9. Therapeutic gene editing: delivery and regulatory perspectives.

    PubMed

    Shim, Gayong; Kim, Dongyoon; Park, Gyu Thae; Jin, Hyerim; Suh, Soo-Kyung; Oh, Yu-Kyoung

    2017-06-01

    Gene-editing technology is an emerging therapeutic modality for manipulating the eukaryotic genome by using target-sequence-specific engineered nucleases. Because of the exceptional advantages that gene-editing technology offers in facilitating the accurate correction of sequences in a genome, gene editing-based therapy is being aggressively developed as a next-generation therapeutic approach to treat a wide range of diseases. However, strategies for precise engineering and delivery of gene-editing nucleases, including zinc finger nucleases, transcription activator-like effector nuclease, and CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats-associated nuclease Cas9), present major obstacles to the development of gene-editing therapies, as with other gene-targeting therapeutics. Currently, viral and non-viral vectors are being studied for the delivery of these nucleases into cells in the form of DNA, mRNA, or proteins. Clinical trials are already ongoing, and in vivo studies are actively investigating the applicability of CRISPR/Cas9 techniques. However, the concept of correcting the genome poses major concerns from a regulatory perspective, especially in terms of safety. This review addresses current research trends and delivery strategies for gene editing-based therapeutics in non-clinical and clinical settings and considers the associated regulatory issues.

  10. Therapeutic gene editing: delivery and regulatory perspectives

    PubMed Central

    Shim, Gayong; Kim, Dongyoon; Park, Gyu Thae; Jin, Hyerim; Suh, Soo-Kyung; Oh, Yu-Kyoung

    2017-01-01

    Gene-editing technology is an emerging therapeutic modality for manipulating the eukaryotic genome by using target-sequence-specific engineered nucleases. Because of the exceptional advantages that gene-editing technology offers in facilitating the accurate correction of sequences in a genome, gene editing-based therapy is being aggressively developed as a next-generation therapeutic approach to treat a wide range of diseases. However, strategies for precise engineering and delivery of gene-editing nucleases, including zinc finger nucleases, transcription activator-like effector nuclease, and CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats-associated nuclease Cas9), present major obstacles to the development of gene-editing therapies, as with other gene-targeting therapeutics. Currently, viral and non-viral vectors are being studied for the delivery of these nucleases into cells in the form of DNA, mRNA, or proteins. Clinical trials are already ongoing, and in vivo studies are actively investigating the applicability of CRISPR/Cas9 techniques. However, the concept of correcting the genome poses major concerns from a regulatory perspective, especially in terms of safety. This review addresses current research trends and delivery strategies for gene editing-based therapeutics in non-clinical and clinical settings and considers the associated regulatory issues. PMID:28392568

  11. Predictors of shoulder dystocia at the time of operative vaginal delivery.

    PubMed

    Palatnik, Anna; Grobman, William A; Hellendag, Madeline G; Janetos, Timothy M; Gossett, Dana R; Miller, Emily S

    2016-11-01

    It remains uncertain whether clinical factors known prior to delivery can predict which women are more likely to experience shoulder dystocia in the setting of operative vaginal delivery. We sought to identify whether shoulder dystocia can be accurately predicted among women undergoing an operative vaginal delivery. This was a case-control study of women undergoing a low or outlet operative vaginal delivery from 2005 through 2014 in a single tertiary care center. Cases were defined as women who experienced a shoulder dystocia at the time of operative vaginal delivery. Controls consisted of women without a shoulder dystocia at the time of operative vaginal delivery. Variables previously identified to be associated with shoulder dystocia that could be known prior to delivery were abstracted from the medical records. Bivariable analyses and multivariable logistic regression were used to identify factors independently associated with shoulder dystocia. A receiver operating characteristic curve was created to evaluate the predictive value of the model for shoulder dystocia. Of the 4080 women who met inclusion criteria, shoulder dystocia occurred in 162 (4.0%) women. In bivariable analysis, maternal age, parity, body mass index, diabetes, chorioamnionitis, arrest disorder as an indication for an operative vaginal delivery, vacuum use, and estimated fetal weight >4 kg were significantly associated with shoulder dystocia. In multivariable analysis, parity, diabetes, chorioamnionitis, arrest disorder as an indication for operative vaginal delivery, vacuum use, and estimated fetal weight >4 kg remained independently associated with shoulder dystocia. The area under the curve for the generated receiver operating characteristic curve was 0.73 (95% confidence interval, 0.69-0.77), demonstrating only a modest ability to predict shoulder dystocia before performing an operative vaginal delivery. While risk factors for shoulder dystocia at the time of operative vaginal delivery

  12. Peptide and protein delivery using new drug delivery systems.

    PubMed

    Jain, Ashish; Jain, Aviral; Gulbake, Arvind; Shilpi, Satish; Hurkat, Pooja; Jain, Sanjay K

    2013-01-01

    Pharmaceutical and biotechnological research sorts protein drug delivery systems by importance based on their various therapeutic applications. The effective and potent action of the proteins/peptides makes them the drugs of choice for the treatment of numerous diseases. Major research issues in protein delivery include the stabilization of proteins in delivery devices and the design of appropriate target-specific protein carriers. Many efforts have been made for effective delivery of proteins/peptidal drugs through various routes of administrations for successful therapeutic effects. Nanoparticles made of biodegradable polymers such as poly lactic acid, polycaprolactone, poly(lactic-co-glycolic acid), the poly(fumaric-co-sebacic) anhydride chitosan, and modified chitosan, as well as solid lipids, have shown great potential in the delivery of proteins/peptidal drugs. Moreover, scientists also have used liposomes, PEGylated liposomes, niosomes, and aquasomes, among others, for peptidal drug delivery. They also have developed hydrogels and transdermal drug delivery systems for peptidal drug delivery. A receptor-mediated delivery system is another attractive strategy to overcome the limitation in drug absorption that enables the transcytosis of the protein across the epithelial barrier. Modification such as PEGnology is applied to various proteins and peptides of the desired protein and peptides also increases the circulating life, solubility and stability, pharmacokinetic properties, and antigenicity of protein. This review focuses on various approaches for effective protein/peptidal drug delivery, with special emphasis on insulin delivery.

  13. Targeting homeostasis in drug delivery using bioresponsive hydrogel microforms.

    PubMed

    Wilson, A Nolan; Guiseppi-Elie, Anthony

    2014-01-30

    A drug delivery platform comprising a biocompatible, bioresponsive hydrogel and possessing a covalently tethered peptide-drug conjugate was engineered to achieve stasis, via a closed control loop, of the external biochemical activity of the actuating protease. The delivery platform contains a peptide-drug conjugate covalently tethered to the hydrogel matrix, which in the presence of the appropriate protease, was cleaved and the drug released into the bathing environment. This platform was developed and investigated in silico using a finite element modeling (FEM) approach. Firstly, the primary governing phenomena guiding drug release profiles were investigated, and it was confirmed that under transport-limited conditions, the diffusion of the enzyme within the hydrogel and the coupled enzyme kinetics accurately model the system and are in agreement with published results. Secondly, the FEM model was used to investigate the release of a competitive protease inhibitor, MAG283, via cleavage of Acetyl-Pro-Leu-Gly|Leu-MAG-283 by MMP9 in order to achieve targeted homeostasis of MMP-9 activity, such as in the pathophysiology of chronic wounds, via closed-loop feedback control. The key engineering parameters for the delivery device are the radii of the hydrogel microspheres and the concentration of the peptide-inhibitor conjugate. Homeostatic drug delivery, where the focus turns away from the drug release rate and turns toward achieving targeted control of biochemical activity within a biochemical pathway, is an emerging approach in drug delivery methodologies for which the potential has not yet been fully realized. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. The Scientific and Societal Need for Accurate Global Remote Sensing of Marine Suspended Sediments

    NASA Technical Reports Server (NTRS)

    Acker, James G.

    2006-01-01

    Population pressure, commercial development, and climate change are expected to cause continuing alteration of the vital oceanic coastal zone environment. These pressures will influence both the geology and biology of the littoral, nearshore, and continental shelf regions. A pressing need for global observation of coastal change processes is an accurate remotely-sensed data product for marine suspended sediments. The concentration, delivery, transport, and deposition of sediments is strongly relevant to coastal primary production, inland and coastal hydrology, coastal erosion, and loss of fragile wetland and island habitats. Sediment transport and deposition is also related to anthropogenic activities including agriculture, fisheries, aquaculture, harbor and port commerce, and military operations. Because accurate estimation of marine suspended sediment concentrations requires advanced ocean optical analysis, a focused collaborative program of algorithm development and assessment is recommended, following the successful experience of data refinement for remotely-sensed global ocean chlorophyll concentrations.

  15. Application of Fused Deposition Modelling (FDM) Method of 3D Printing in Drug Delivery.

    PubMed

    Long, Jingjunjiao; Gholizadeh, Hamideh; Lu, Jun; Bunt, Craig; Seyfoddin, Ali

    2017-01-01

    Three-dimensional (3D) printing is an emerging manufacturing technology for biomedical and pharmaceutical applications. Fused deposition modelling (FDM) is a low cost extrusion-based 3D printing technique that can deposit materials layer-by-layer to create solid geometries. This review article aims to provide an overview of FDM based 3D printing application in developing new drug delivery systems. The principle methodology, suitable polymers and important parameters in FDM technology and its applications in fabrication of personalised tablets and drug delivery devices are discussed in this review. FDM based 3D printing is a novel and versatile manufacturing technique for creating customised drug delivery devices that contain accurate dose of medicine( s) and provide controlled drug released profiles. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Interventional MRI-guided catheter placement and real time drug delivery to the central nervous system.

    PubMed

    Han, Seunggu J; Bankiewicz, Krystof; Butowski, Nicholas A; Larson, Paul S; Aghi, Manish K

    2016-06-01

    Local delivery of therapeutic agents into the brain has many advantages; however, the inability to predict, visualize and confirm the infusion into the intended target has been a major hurdle in its clinical development. Here, we describe the current workflow and application of the interventional MRI (iMRI) system for catheter placement and real time visualization of infusion. We have applied real time convection-enhanced delivery (CED) of therapeutic agents with iMRI across a number of different clinical trials settings in neuro-oncology and movement disorders. Ongoing developments and accumulating experience with the technique and technology of drug formulations, CED platforms, and iMRI systems will continue to make local therapeutic delivery into the brain more accurate, efficient, effective and safer.

  17. Delivery room triage of large for gestational age infants of diabetic mothers.

    PubMed

    Cordero, Leandro; Rath, Krista; Zheng, Katherine; Landon, Mark B; Nankervis, Craig A

    2014-01-01

    To review our 4-year experience (2008-2011) with delivery room triage of large for gestational age infants of diabetic mothers. Retrospective cohort investigation of 311 large for gestational age infants of diabetic mothers (White's Class A1 (77), A2 (87), B (77), and C-R (70)). Of 311 women, 31% delivered at 34-36 weeks gestational age and 69% at term. While 70% were delivered by cesarean, 30% were vaginal deliveries. A total of 160 asymptomatic infants were triaged from the delivery room to the well baby nursery. Of these, 55 (34%) developed hypoglycemia. In 43 cases, the hypoglycemia was corrected by early feedings; in the remaining 12, intravenous dextrose treatment was required. A total of 151 infants were triaged from the delivery room to the neonatal intensive care unit. Admission diagnoses included respiratory distress (51%), prevention of hypoglycemia (27%), prematurity (21%), and asphyxia (1%). Hypoglycemia affected 66 (44%) of all neonatal intensive care unit infants. Safe triage of asymptomatic large for gestational age infants of diabetic mothers from the delivery room to well baby nursery can be accomplished in the majority of cases. Those infants in need of specialized care can be accurately identified and effectively treated in the neonatal intensive care unit setting.

  18. Transdermal drug delivery

    PubMed Central

    Prausnitz, Mark R.; Langer, Robert

    2009-01-01

    Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, non-cavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin’s barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase impact on medicine. PMID:18997767

  19. Expanding Alternative Delivery Systems.

    ERIC Educational Resources Information Center

    Baltzer, Jan A.

    Alternative educational delivery systems that might be useful to community colleges are considered. The following categories of delivery systems are covered: broadcast delivery systems; copy delivery systems, print delivery systems, computer delivery systems, telephone delivery systems, and satellites. Among the applications for broadcast…

  20. SU-F-J-193: Efficient Dose Extinction Method for Water Equivalent Path Length (WEPL) of Real Tissue Samples for Validation of CT HU to Stopping Power Conversion

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

    Zhang, R; Baer, E; Jee, K

    Purpose: For proton therapy, an accurate model of CT HU to relative stopping power (RSP) conversion is essential. In current practice, validation of these models relies solely on measurements of tissue substitutes with standard compositions. Validation based on real tissue samples would be much more direct and can address variations between patients. This study intends to develop an efficient and accurate system based on the concept of dose extinction to measure WEPL and retrieve RSP in biological tissue in large number of types. Methods: A broad AP proton beam delivering a spread out Bragg peak (SOBP) is used to irradiatemore » the samples with a Matrixx detector positioned immediately below. A water tank was placed on top of the samples, with the water level controllable in sub-millimeter by a remotely controlled dosing pump. While gradually lowering the water level with beam on, the transmission dose was recorded at 1 frame/sec. The WEPL were determined as the difference between the known beam range of the delivered SOBP (80%) and the water level corresponding to 80% of measured dose profiles in time. A Gammex 467 phantom was used to test the system and various types of biological tissue was measured. Results: RSP for all Gammex inserts, expect the one made with lung-450 material (<2% error), were determined within ±0.5% error. Depends on the WEPL of investigated phantom, a measurement takes around 10 min, which can be accelerated by a faster pump. Conclusion: Based on the concept of dose extinction, a system was explored to measure WEPL efficiently and accurately for a large number of samples. This allows the validation of CT HU to stopping power conversions based on large number of samples and real tissues. It also allows the assessment of beam uncertainties due to variations over patients, which issue has never been sufficiently studied before.« less

  1. Positron Emission Tomography Image-Guided Drug Delivery: Current Status and Future Perspectives

    PubMed Central

    2015-01-01

    Positron emission tomography (PET) is an important modality in the field of molecular imaging, which is gradually impacting patient care by providing safe, fast, and reliable techniques that help to alter the course of patient care by revealing invasive, de facto procedures to be unnecessary or rendering them obsolete. Also, PET provides a key connection between the molecular mechanisms involved in the pathophysiology of disease and the according targeted therapies. Recently, PET imaging is also gaining ground in the field of drug delivery. Current drug delivery research is focused on developing novel drug delivery systems with emphasis on precise targeting, accurate dose delivery, and minimal toxicity in order to achieve maximum therapeutic efficacy. At the intersection between PET imaging and controlled drug delivery, interest has grown in combining both these paradigms into clinically effective formulations. PET image-guided drug delivery has great potential to revolutionize patient care by in vivo assessment of drug biodistribution and accumulation at the target site and real-time monitoring of the therapeutic outcome. The expected end point of this approach is to provide fundamental support for the optimization of innovative diagnostic and therapeutic strategies that could contribute to emerging concepts in the field of “personalized medicine”. This review focuses on the recent developments in PET image-guided drug delivery and discusses intriguing opportunities for future development. The preclinical data reported to date are quite promising, and it is evident that such strategies in cancer management hold promise for clinically translatable advances that can positively impact the overall diagnostic and therapeutic processes and result in enhanced quality of life for cancer patients. PMID:24865108

  2. Accuracy of Blood Loss Measurement during Cesarean Delivery.

    PubMed

    Doctorvaladan, Sahar V; Jelks, Andrea T; Hsieh, Eric W; Thurer, Robert L; Zakowski, Mark I; Lagrew, David C

    2017-04-01

    Objective  This study aims to compare the accuracy of visual, quantitative gravimetric, and colorimetric methods used to determine blood loss during cesarean delivery procedures employing a hemoglobin extraction assay as the reference standard. Study Design  In 50 patients having cesarean deliveries blood loss determined by assays of hemoglobin content on surgical sponges and in suction canisters was compared with obstetricians' visual estimates, a quantitative gravimetric method, and the blood loss determined by a novel colorimetric system. Agreement between the reference assay and other measures was evaluated by the Bland-Altman method. Results  Compared with the blood loss measured by the reference assay (470 ± 296 mL), the colorimetric system (572 ± 334 mL) was more accurate than either visual estimation (928 ± 261 mL) or gravimetric measurement (822 ± 489 mL). The correlation between the assay method and the colorimetric system was more predictive (standardized coefficient = 0.951, adjusted R 2  = 0.902) than either visual estimation (standardized coefficient = 0.700, adjusted R 2  = 00.479) or the gravimetric determination (standardized coefficient = 0.564, adjusted R 2  = 0.304). Conclusion  During cesarean delivery, measuring blood loss using colorimetric image analysis is superior to visual estimation and a gravimetric method. Implementation of colorimetric analysis may enhance the ability of management protocols to improve clinical outcomes.

  3. Accuracy of Blood Loss Measurement during Cesarean Delivery

    PubMed Central

    Doctorvaladan, Sahar V.; Jelks, Andrea T.; Hsieh, Eric W.; Thurer, Robert L.; Zakowski, Mark I.; Lagrew, David C.

    2017-01-01

    Objective This study aims to compare the accuracy of visual, quantitative gravimetric, and colorimetric methods used to determine blood loss during cesarean delivery procedures employing a hemoglobin extraction assay as the reference standard. Study Design In 50 patients having cesarean deliveries blood loss determined by assays of hemoglobin content on surgical sponges and in suction canisters was compared with obstetricians' visual estimates, a quantitative gravimetric method, and the blood loss determined by a novel colorimetric system. Agreement between the reference assay and other measures was evaluated by the Bland–Altman method. Results Compared with the blood loss measured by the reference assay (470 ± 296 mL), the colorimetric system (572 ± 334 mL) was more accurate than either visual estimation (928 ± 261 mL) or gravimetric measurement (822 ± 489 mL). The correlation between the assay method and the colorimetric system was more predictive (standardized coefficient = 0.951, adjusted R2 = 0.902) than either visual estimation (standardized coefficient = 0.700, adjusted R2 = 00.479) or the gravimetric determination (standardized coefficient = 0.564, adjusted R2 = 0.304). Conclusion During cesarean delivery, measuring blood loss using colorimetric image analysis is superior to visual estimation and a gravimetric method. Implementation of colorimetric analysis may enhance the ability of management protocols to improve clinical outcomes. PMID:28497007

  4. Dual delivery of hydrophilic and hydrophobic drugs from chitosan/diatomaceous earth composite membranes.

    PubMed

    López-Cebral, Rita; Peng, Guangjia; Reys, Lara L; Silva, Simone S; Oliveira, Joaquim M; Chen, Jie; Silva, Tiago H; Reis, Rui L

    2018-02-02

    Oral administration of drugs presents important limitations, which are frequently not granted the importance that they really have. For instance, hepatic metabolism means an important drug loss, while some patients have their ability to swell highly compromised (i.e. unconsciousness, cancer…). Sublingual placement of an accurate Pharmaceutical Dosage Form is an attractive alternative. This work explores the use of the β-chitosan membranes, from marine industry residues, composed with marine sediments for dual sublingual drug delivery. As proof of concept, the membranes were loaded with a hydrophilic (gentamicin) and a hydrophobic (dexamethasone) drug. The physico-chemical and morphological characterization indicated the successful incorporated of diatomaceous earth within the chitosan membranes. Drug delivery studies showed the potential of all formulations for the immediate release of hydrophilic drugs, while diatomaceous earth improved the loading and release of the hydrophobic drug. These results highlight the interest of the herein developed membranes for dual drug delivery.

  5. Facilitating process changes in meal delivery and radiological testing to improve inpatient insulin timing using six sigma method.

    PubMed

    Yamamoto, J Jay; Malatestinic, Bill; Lehman, Angela; Juneja, Rattan

    2010-01-01

    The objective of this project was to improve the timing of inpatient insulin administration related to meal delivery and the scheduling of radiology tests by Lean Six Sigma method. A multidisciplinary hospital team and a Six Sigma team from a pharmaceutical manufacturer collaborated to evaluate food delivery and radiology scheduling processes related to the timing of insulin administration. Key factors leading to problems within each system were addressed to improve the efficiency of each process while improving the timeliness of glucose testing and insulin administration. Standardizing the food delivery schedule and utilizing scorecards to track on-time meal deliveries to the floor enabled nursing to more accurately administer insulin in coordination with the delivery of meals. Increasing communication and restricting the scheduling of inpatient procedures during mealtimes reduced disruptions to insulin administration. Data at 6 months postimplementation demonstrated that the institution met goals for most primary outcome metrics including increasing on-time meal delivery and the proportion of patients taking insulin scheduled for radiology tests during appropriate times. By implementing the recommendations identified via Lean Six Sigma, this collaborative effort improved the timing of inpatient insulin administration related to meal delivery and radiology testing.

  6. Noninvasive Uterine Electromyography For Prediction of Preterm Delivery*

    PubMed Central

    UCOVNIK, Miha L; MANER, William L.; CHAMBLISS, Linda R.; BLUMRICK, Richard; BALDUCCI, James; NOVAK-ANTOLIC, Ziva; GARFIELD, Robert E.

    2011-01-01

    Objective Power spectrum (PS) of uterine electromyography (EMG) can identify true labor. EMG propagation velocity (PV) to diagnose labor has not been reported. The objective was to compare uterine EMG against current methods to predict preterm delivery. Study design EMG was recorded in 116 patients (preterm labor, n=20; preterm non-labor, n=68; term labor, n=22; term non-labor, n=6). Student’s t-test was used to compare EMG values for labor vs. non-labor (P<0.05 significant). Predictive values of EMG, Bishop-score, contractions on tocogram, and transvaginal cervical length were calculated using receiver-operator-characteristics analysis. Results PV was higher in preterm and term labor compared with non-labor (P<0.001). Combined PV and PS peak frequency predicted preterm delivery within 7 days with area-under-the-curve (AUC) = 0.96. Bishop score, contractions, and cervical length had AUC of 0.72, 0.67, and 0.54. Conclusions Uterine EMG PV and PS peak frequency more accurately identify true preterm labor than clinical methods. PMID:21145033

  7. SU-E-T-481: Dosimetric Effects of Tissue Heterogeneity in Proton Therapy: Monte Carlo Simulation and Experimental Study Using Animal Tissue Phantoms.

    PubMed

    Liu, Y; Zheng, Y

    2012-06-01

    Accurate determination of proton dosimetric effect for tissue heterogeneity is critical in proton therapy. Proton beams have finite range and consequently tissue heterogeneity plays a more critical role in proton therapy. The purpose of this study is to investigate the tissue heterogeneity effect in proton dosimetry based on anatomical-based Monte Carlo simulation using animal tissues. Animal tissues including a pig head and beef bulk were used in this study. Both pig head and beef were scanned using a GE CT scanner with 1.25 mm slice thickness. A treatment plan was created, using the CMS XiO treatment planning system (TPS) with a single proton spread-out-Bragg-peak beam (SOBP). Radiochromic films were placed at the distal falloff region. Image guidance was used to align the phantom before proton beams were delivered according to the treatment plan. The same two CT sets were converted to Monte Carlo simulation model. The Monte Carlo simulated dose calculations with/without tissue omposition were compared to TPS calculations and measurements. Based on the preliminary comparison, at the center of SOBP plane, the Monte Carlo simulation dose without tissue composition agreed generally well with TPS calculation. In the distal falloff region, the dose difference was large, and about 2 mm isodose line shift was observed with the consideration of tissue composition. The detailed comparison of dose distributions between Monte Carlo simulation, TPS calculations and measurements is underway. Accurate proton dose calculations are challenging in proton treatment planning for heterogeneous tissues. Tissue heterogeneity and tissue composition may lead to isodose line shifts up to a few millimeters in the distal falloff region. By simulating detailed particle transport and energy deposition, Monte Carlo simulations provide a verification method in proton dose calculation where inhomogeneous tissues are present. © 2012 American Association of Physicists in Medicine.

  8. Photo-synthesis of protein-based nanoparticles and the application in drug delivery

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

    Xie, Jinbing; Wang, Hongyang; Cao, Yi

    Recently, protein-based nanoparticles as drug delivery systems have attracted great interests due to the excellent behavior of high biocompatibility and biodegradability, and low toxicity. However, the synthesis techniques are generally costly, chemical reagents introduced, and especially present difficulties in producing homogeneous monodispersed nanoparticles. Here, we introduce a novel physical method to synthesize protein nanoparticles which can be accomplished under physiological condition only through ultraviolet (UV) illumination. By accurately adjusting the intensity and illumination time of UV light, disulfide bonds in proteins can be selectively reduced and the subsequent self-assembly process can be well controlled. Importantly, the co-assembly can also bemore » dominated when the proteins mixed with either anti-cancer drugs, siRNA, or active targeting molecules. Both in vitro and in vivo experiments indicate that our synthesized protein–drug nanoparticles (drug-loading content and encapsulation efficiency being ca. 8.2% and 70%, respectively) not only possess the capability of traditional drug delivery systems (DDS), but also have a greater drug delivery efficiency to the tumor sites and a better inhibition of tumor growth (only 35% of volume comparing to the natural growing state), indicating it being a novel drug delivery system in tumor therapy.« less

  9. SU-E-T-515: Investigating the Linear Energy Transfer Dependency of Different PRESAGE Formulations in a Proton Beam

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

    Carroll, M; Alqathami, M; Blencowe, A

    Purpose Previous studies have reported an under-response of PRESAGE in a proton beam as a Result of the extremely high LET in the distal end of the spread out Bragg peak (SOBP). This work is a preliminary investigation to quantify the effect of the formulation, specifically the concentration of halocarbon radical initiator relative to leuco dye, on radical recombination resulting in LET dependence. Methods The traditional PRESAGE formulation developed by Heuris Pharma was altered to constitute radical initiator concentrations of 5, 15, and 30% (low, medium, and high) by weight with all other components balanced to maintain proportionality. Chloroform wasmore » specifically examined in this study and all dosimeters were made in-house. Cylindrical PRESAGE dosimeters (3.5cm diameter and 6cm length) were made for each formulation and irradiated by a 200-MeV proton beam to 500 cGy across a 2cm SOBP. Dosimeters were read out using the DMOS optical-CT scanner. The dose distributions were analyzed and dose profiles were used to compare the relative dose response to find the stability across the high-LET region of the SOBP. LET dependence was measured by the variation to ion chamber measurements for the final 25% of the SOBP (∼0.5cm) prior to the distal-90 of each profile. Results Relative to ion chamber data, all PRESAGE dosimeters showed an under-response at the distal end of the SOBP. The medium concentration formulation matched most closely with an average 8.3% under-response closely followed by the low concentration at 12.2% and then the high concentration at 22.8%. In all three cases, the highest points of discrepancy were in the distal most regions. Conclusion The radical initiator concentration in PRESAGE can be tailored to reduce the LET dependence in a proton beam. This warrants further study to quantify comprehensively the effect of concentration of different halocarbon radical initiators on LET dependency. Grant number 5RO1CA100835.« less

  10. SU-E-T-671: Range-Modulation Effects of Carbon Ion Beams in Lung Tissue

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

    Witt, M; Weber, U; Simeonov, Y

    Purpose: When particles traversing inhomogeneous materials like lung they show a characteristic range modulation which cannot be observed in homogeneous materials. It is possible to describe the range modulation by a convolution of an unperturbed Bragg-Curve and a normal distribution. The sigma of the normal distribution is a parameter for the strength of the modulation effect. A new material parameter (modulation power, P-mod) is introduced which is independent of the material thickness. It is defined as the square of sigma divided by the mean water equivalent thickness of the target (µ). Methods: The modulation power of lung tissue was determinedmore » by actual Bragg-peak measurements after traversing an ex-vivo porcine lung and by Monte-Carlo simulations with micro-CT data of human lung tissue. The determined modulation powers were used to show the effect of range modulation effects in a simplified treatment situation. A four centimeter spread-out Bragg-peak after traversing eight centimeter of lung tissue was simulated in FLUKA. The SOBP with and without consideration of range modulation effects were compared. Results: As well in the measurements as in the MC simulations range modulation effects of lung tissue were observed. The determined modulation powers showed a great range from 0.05 mm, in the micro-CT data, to 0.7 mm in the lung measurements. The SOBP comparison showed that range modulation effects Result in over- and underdosages at the distal and proximal edge of the SOBP. In the investigated case, the last 0.5 cm of the SOBP showed an underdosage of up to 50% at the distal edge, while 0.5 cm distal to the SOBP an overdosage of up to 50% was observed. Conclusion: Range modulation effects occur in inhomogeneous materials like lung. These modulation effects may Result in clinically relevant over- and underdosages but are currently not considered in commercially available treatment planning systems.« less

  11. Structural and thermodynamic insights into β-1,2-glucooligosaccharide capture by a solute-binding protein in Listeria innocua.

    PubMed

    Abe, Koichi; Sunagawa, Naoki; Terada, Tohru; Takahashi, Yuta; Arakawa, Takatoshi; Igarashi, Kiyohiko; Samejima, Masahiro; Nakai, Hiroyuki; Taguchi, Hayao; Nakajima, Masahiro; Fushinobu, Shinya

    2018-06-08

    β-1,2-Glucans are bacterial carbohydrates that exist in cyclic or linear forms and play an important role in infections and symbioses involving Gram-negative bacteria. Although several β-1,2-glucan-associated enzymes have been characterized, little is known about how β-1,2-glucan and its shorter oligosaccharides (Sop n s) are captured and imported into the bacterial cell. Here, we report the biochemical and structural characteristics of the Sop n -binding protein (SO-BP, Lin1841) associated with the ATP-binding cassette (ABC) transporter from the Gram-positive bacterium Listeria innocua Calorimetric analysis revealed that SO-BP specifically binds to Sop n s with a degree of polymerization of 3 or more, with K d values in the micromolar range. The crystal structures of SO-BP in an unliganded open form and in closed complexes with tri-, tetra-, and pentaoligosaccharides (Sop 3-5 ) were determined to a maximum resolution of 1.6 Å. The binding site displayed shape complementarity to Sop n , which adopted a zigzag conformation. We noted that water-mediated hydrogen bonds and stacking interactions play a pivotal role in the recognition of Sop 3-5 by SO-BP, consistent with its binding thermodynamics. Computational free-energy calculations and a mutational analysis confirmed that interactions with the third glucose moiety of Sop n s are significantly responsible for ligand binding. A reduction in unfavorable changes in binding entropy that were in proportion to the lengths of the Sop n s was explained by conformational entropy changes. Phylogenetic and sequence analyses indicated that SO-BP ABC transporter homologs, glycoside hydrolases, and other related proteins are co-localized in the genomes of several bacteria. This study may improve our understanding of bacterial β-1,2-glucan metabolism and promote the discovery of unidentified β-1,2-glucan-associated proteins. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Ocular delivery of macromolecules

    PubMed Central

    Kim, Yoo-Chun; Chiang, Bryce; Wu, Xianggen; Prausnitz, Mark R.

    2014-01-01

    Biopharmaceuticals are making increasing impact on medicine, including treatment of indications in the eye. Macromolecular drugs are typically given by physician-administered invasive delivery methods, because non--invasive ocular delivery methods, such as eye drops, and systemic delivery, have low bioavailability and/or poor ocular targeting. There is a need to improve delivery of biopharmaceuticals to enable less-invasive delivery routes, less-frequent dosing through controlled-release drug delivery and improved drug targeting within the eye to increase efficacy and reduce side effects. This review discusses the barriers to drug delivery via various ophthalmic routes of administration in the context of macromolecule delivery and discusses efforts to develop controlled-release systems for delivery of biopharmaceuticals to the eye. The growing number of macromolecular therapies in the eye needs improved drug delivery methods that increase drug efficacy, safety and patient compliance. PMID:24998941

  13. Accurate recognition and effective treatment of ventricular fibrillation by automated external defibrillators in adolescents.

    PubMed

    Atkins, D L; Hartley, L L; York, D K

    1998-03-01

    To evaluate the accuracy and efficacy of automated external defibrillators (AEDs) in patients <16 years old. AEDs are standard therapy in out-of-hospital resuscitation of adults and have led to higher success rates. Their use in children and adolescents has never been evaluated, despite recommendations from the American Heart Association that they be used in children >8 years of age. This was a retrospective cohort study of children <16 years old who underwent out-of-hospital cardiac resuscitation and on whom an AED was used during the resuscitation. The setting was rural and urban prehospital emergency medical systems. Patients were identified by review of a database of cardiac arrests maintained by a large surveillance program of these services. AEDs were used to assess cardiac rhythm in 18 patients with a mean age of 12.1 +/- 3.7 years. The cardiac rhythms were analyzed 67 times and included ventricular fibrillation (25), asystole/pulseless electrical activity (32), sinus bradycardia (6), and sinus tachycardia (4). The AEDs recognized all nonshockable rhythms accurately and advised no shock. Ventricular fibrillation was recognized accurately in 22 (88%) of 25 episodes and advised or administered a shock 22 times. Sensitivity and specificity for accurate rhythm analysis were 88% and 100%, respectively. One patient with a nonshockable rhythm survived, whereas 3 of 9 patients with ventricular fibrillation survived. These data furnish evidence that AEDs provide accurate rhythm detection and shock delivery to children and young adolescents. AED use is potentially as effective for children as it is for adults.

  14. Predicting clinical image delivery time by monitoring PACS queue behavior.

    PubMed

    King, Nelson E; Documet, Jorge; Liu, Brent

    2006-01-01

    The expectation of rapid image retrieval from PACS users contributes to increased information technology (IT) infrastructure investments to increase performance as well as continuing demands upon PACS administrators to respond to "slow" system performance. The ability to provide predicted delivery times to a PACS user may curb user expectations for "fastest" response especially during peak hours. This, in turn, could result in a PACS infrastructure tailored to more realistic performance demands. A PACS with a stand-alone architecture under peak load typically holds study requests in a queue until the DICOM C-Move command can take place. We investigate the contents of a stand-alone architecture PACS RetrieveSend queue and identified parameters and behaviors that enable a more accurate prediction of delivery time. A prediction algorithm for studies delayed in a stand-alone PACS queue can be extendible to other potential bottlenecks such as long-term storage archives. Implications of a queue monitor in other PACS architectures are also discussed.

  15. Radiation dose delivery verification in the treatment of carcinoma-cervix

    NASA Astrophysics Data System (ADS)

    Shrotriya, D.; Kumar, S.; Srivastava, R. N. L.

    2015-06-01

    The accurate dose delivery to the clinical target volume in radiotherapy can be affected by various pelvic tissues heterogeneities. An in-house heterogeneous woman pelvic phantom was designed and used to verify the consistency and computational capability of treatment planning system of radiation dose delivery in the treatment of cancer cervix. Oncentra 3D-TPS with collapsed cone convolution (CCC) dose calculation algorithm was used to generate AP/PA and box field technique plan. the radiation dose was delivered by Primus Linac (Siemens make) employing high energy 15 MV photon beam by isocenter technique. A PTW make, 0.125cc ionization chamber was used for direct measurements at various reference points in cervix, bladder and rectum. The study revealed that maximum variation between computed and measured dose at cervix reference point was 1% in both the techniques and 3% and 4% variation in AP/PA field and 5% and 4.5% in box technique at bladder and rectum points respectively.

  16. Ridge filter design and optimization for the broad-beam three-dimensional irradiation system for heavy-ion radiotherapy.

    PubMed

    Schaffner, B; Kanai, T; Futami, Y; Shimbo, M; Urakabe, E

    2000-04-01

    The broad-beam three-dimensional irradiation system under development at National Institute of Radiological Sciences (NIRS) requires a small ridge filter to spread the initially monoenergetic heavy-ion beam to a small spread-out Bragg peak (SOBP). A large SOBP covering the target volume is then achieved by a superposition of differently weighted and displaced small SOBPs. Two approaches were studied for the definition of a suitable ridge filter and experimental verifications were performed. Both approaches show a good agreement between the calculated and measured dose and lead to a good homogeneity of the biological dose in the target. However, the ridge filter design that produces a Gaussian-shaped spectrum of the particle ranges was found to be more robust to small errors and uncertainties in the beam application. Furthermore, an optimization procedure for two fields was applied to compensate for the missing dose from the fragmentation tail for the case of a simple-geometry target. The optimized biological dose distributions show that a very good homogeneity is achievable in the target.

  17. Ferritin nanocages: A biological platform for drug delivery, imaging and theranostics in cancer.

    PubMed

    Truffi, Marta; Fiandra, Luisa; Sorrentino, Luca; Monieri, Matteo; Corsi, Fabio; Mazzucchelli, Serena

    2016-05-01

    Nowadays cancer represents a prominent challenge in clinics. Main achievements in cancer management would be the development of highly accurate and specific diagnostic tools for early detection of cancer onset, and the generation of smart drug delivery systems for targeted chemotherapy release in cancer cells. In this context, protein-based nanocages hold a tremendous potential as devices for theranostics purposes. In particular, ferritin has emerged as an excellent and promising protein-based nanocage thanks to its unique architecture, surface properties and high biocompatibility. By exploiting natural recognition of the Transferrin Receptor 1, which is overexpressed on tumor cells, ferritin nanocages may ensure a proper drug delivery and release. Moreover, researchers have applied surface functionalities on ferritin cages for further providing active tumor targeting. Encapsulation strategies of non metal-containing drugs within ferritin cages have been explored and successfully performed with encouraging results. Various preclinical studies have demonstrated that nanoformulation within ferritin nanocages significantly improved targeted therapy and accurate imaging of cancer cells. Aims of this review are to describe structure and functions of ferritin nanocages, and to provide an overview about the nanotechnological approaches implemented for applying them to cancer diagnosis and treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Buccal drug delivery.

    PubMed

    Smart, John D

    2005-05-01

    Buccal formulations have been developed to allow prolonged localised therapy and enhanced systemic delivery. The buccal mucosa, however, while avoiding first-pass effects, is a formidable barrier to drug absorption, especially for biopharmaceutical products (proteins and oligonucleotides) arising from the recent advances in genomics and proteomics. The buccal route is typically used for extended drug delivery, so formulations that can be attached to the buccal mucosa are favoured. The bioadhesive polymers used in buccal drug delivery to retain a formulation are typically hydrophilic macro-molecules containing numerous hydrogen bonding groups. Newer second-generation bioadhesives have been developed and these include modified or new polymers that allow enhanced adhesion and/or drug delivery, in addition to site-specific ligands such as lectins. Over the last 20 years a wide range of formulations has been developed for buccal drug delivery (tablet, patch, liquids and semisolids) but comparatively few have found their way onto the market. Currently, this route is restricted to the delivery of a limited number of small lipophilic molecules that readily cross the buccal mucosa. However, this route could become a significant means for the delivery of a range of active agents in the coming years, if the barriers to buccal drug delivery are overcome. In particular, patient acceptability and the successful systemic delivery of large molecules (proteins, oligonucleotides and polysaccharides) via this route remains both a significant opportunity and challenge, and new/improved technologies may be required to address these.

  19. Progress in the Field of Constructing Near-Infrared Light-Responsive Drug Delivery Platforms.

    PubMed

    Zhou, Fang; Wang, Hanjie; Chang, Jin

    2016-03-01

    Stimuli-responsive materials have taken replace of traditional drug carriers due to their ability to achieve controlled release of their encapsulated contents. A variety of sensitive materials, such as polymers that respond to pH, light, and magnetic fields, are widely used to construct drug carriers, and achieved good results. Specifically, near-infrared light (NIR) responsive materials are of particular interest in drug delivery, as NIR can penetrate body tissue and is minimally absorbed by the body's water and hemoglobin and is less harmful to healthy cells than UV or visible light. Thus, the near-infrared excitation drug delivery systems (NIRDDSs) have some essential advantages just like being efficient to kill tumor cells, accurate to achieve the tumor sites and less damage to human body. Also, in the process of building the carriers, we may achieve a combination of controlled release chemotherapy, photothermal therapy (PTT) or photodynamic therapy (PDT). In addition, besides utilizing as drug delivery platforms, some carriers can achieve multifunctional tumor diagnosis and treatment, such as magnetic resonance imaging, optical imaging, drug carriers and PTT. In this review, based on the mechanism of NIR, we highlight diverse near-infrared light-responsive drug delivery platforms and recent advances in the development of NIRDDSs for cancer therapy primarily.

  20. Designing a range modulator wheel to spread-out the Bragg peak for a passive proton therapy facility

    NASA Astrophysics Data System (ADS)

    Jia, S. Bijan; Romano, F.; Cirrone, Giuseppe A. P.; Cuttone, G.; Hadizadeh, M. H.; Mowlavi, A. A.; Raffaele, L.

    2016-01-01

    In proton beam therapy, a Spread-Out Bragg peak (SOBP) is used to establish a uniform dose distribution in the target volume. In order to create a SOBP, several Bragg peaks of different ranges, corresponding to different entrance energies, with certain intensities (weights) should be combined each other. In a passive beam scattering system, the beam is usually extracted from a cyclotron at a constant energy throughout a treatment. Therefore, a SOBP is produced by a range modulator wheel, which is basically a rotating wheel with steps of variable thicknesses, or by using the ridge filters. In this study, we used the Geant4 toolkit to simulate a typical passive scattering beam line. In particular, the CATANA transport beam line of INFN Laboratori Nazionali del Sud (LNS) in Catania has been reproduced in this work. Some initial properties of the entrance beam have been checked by benchmarking simulations with experimental data. A class dedicated to the simulation of the wheel modulators has been implemented. It has been designed in order to be easily modified for simulating any desired modulator wheel and, hence, any suitable beam modulation. By using some auxiliary range-shifters, a set of pristine Bragg peaks was obtained from the simulations. A mathematical algorithm was developed, using the simulated pristine dose profiles as its input, to calculate the weight of each pristine peak, reproduce the SOBP, and finally generate a flat dose distribution. Therefore, once the designed modulator has been realized, it has been tested at CATANA facility, comparing the experimental data with the simulation results.

  1. Variations in the Processing of DNA Double-Strand Breaks Along 60-MeV Therapeutic Proton Beams

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

    Chaudhary, Pankaj; Marshall, Thomas I.; Currell, Frederick J.

    Purpose: To investigate the variations in induction and repair of DNA damage along the proton path, after a previous report on the increasing biological effectiveness along clinically modulated 60-MeV proton beams. Methods and Materials: Human skin fibroblast (AG01522) cells were irradiated along a monoenergetic and a modulated spread-out Bragg peak (SOBP) proton beam used for treating ocular melanoma at the Douglas Cyclotron, Clatterbridge Centre for Oncology, Wirral, Liverpool, United Kingdom. The DNA damage response was studied using the 53BP1 foci formation assay. The linear energy transfer (LET) dependence was studied by irradiating the cells at depths corresponding to entrance, proximal, middle, andmore » distal positions of SOBP and the entrance and peak position for the pristine beam. Results: A significant amount of persistent foci was observed at the distal end of the SOBP, suggesting complex residual DNA double-strand break damage induction corresponding to the highest LET values achievable by modulated proton beams. Unlike the directly irradiated, medium-sharing bystander cells did not show any significant increase in residual foci. Conclusions: The DNA damage response along the proton beam path was similar to the response of X rays, confirming the low-LET quality of the proton exposure. However, at the distal end of SOBP our data indicate an increased complexity of DNA lesions and slower repair kinetics. A lack of significant induction of 53BP1 foci in the bystander cells suggests a minor role of cell signaling for DNA damage under these conditions.« less

  2. Rapid Assembly of Customized TALENs into Multiple Delivery Systems

    PubMed Central

    Zhang, Zhengxing; Zhang, Siliang; Huang, Xin; Orwig, Kyle E.; Sheng, Yi

    2013-01-01

    Transcriptional activator-like effector nucleases (TALENs) have become a powerful tool for genome editing. Here we present an efficient TALEN assembly approach in which TALENs are assembled by direct Golden Gate ligation into Gateway® Entry vectors from a repeat variable di-residue (RVD) plasmid array. We constructed TALEN pairs targeted to mouse Ddx3 subfamily genes, and demonstrated that our modified TALEN assembly approach efficiently generates accurate TALEN moieties that effectively introduce mutations into target genes. We generated “user friendly” TALEN Entry vectors containing TALEN expression cassettes with fluorescent reporter genes that can be efficiently transferred via Gateway (LR) recombination into different delivery systems. We demonstrated that the TALEN Entry vectors can be easily transferred to an adenoviral delivery system to expand application to cells that are difficult to transfect. Since TALENs work in pairs, we also generated a TALEN Entry vector set that combines a TALEN pair into one PiggyBac transposon-based destination vector. The approach described here can also be modified for construction of TALE transcriptional activators, repressors or other functional domains. PMID:24244669

  3. Timing of delivery after external cephalic version and the risk for cesarean delivery.

    PubMed

    Kabiri, Doron; Elram, Tamar; Aboo-Dia, Mushira; Elami-Suzin, Matan; Elchalal, Uriel; Ezra, Yossef

    2011-08-01

    To estimate the association between time of delivery after external cephalic version at term and the risk for cesarean delivery. This retrospective cohort study included all successful external cephalic versions performed in a tertiary center between January 1997 and January 2010. Stepwise logistic regression was used to calculate the odds ratio (OR) for cesarean delivery. We included 483 external cephalic versions in this study, representing 53.1% of all external cephalic version attempts. The incidence of cesarean delivery for 139 women (29%) who gave birth less than 96 hours from external cephalic version was 16.5%; for 344 women (71%) who gave birth greater than 96 hours from external cephalic version, the incidence of cesarean delivery was 7.8% (P = .004). The adjusted OR for cesarean delivery was 2.541 (95% confidence interval 1.36-4.72). When stratified by parity, the risk for cesarean delivery when delivery occurred less than 96 hours after external cephalic version was 2.97 and 2.28 for nulliparous and multiparous women, respectively. Delivery at less than 96 hours after successful external cephalic version was associated with an increased risk for cesarean delivery. III.

  4. Resource Consumption of a Diffusion Model for Prevention Programs: The PROSPER Delivery System

    PubMed Central

    Crowley, Daniel M.; Jones, Damon E.; Greenberg, Mark T.; Feinberg, Mark E.; Spoth, Richard L.

    2012-01-01

    Purpose To prepare public systems to implement evidence-based prevention programs for adolescents, it is necessary to have accurate estimates of programs’ resource consumption. When evidence-based programs are implemented through a specialized prevention delivery system, additional costs may be incurred during cultivation of the delivery infrastructure. Currently, there is limited research on the resource consumption of such delivery systems and programs. In this article, we describe the resource consumption of implementing the PROSPER (PROmoting School–Community–University Partnerships to Enhance Resilience) delivery system for a period of 5 years in one state, and how the financial and economic costs of its implementation affect local communities as well as the Cooperative Extension and University systems. Methods We used a six-step framework for conducting cost analysis, using a Cost–Procedure–Process–Outcome Analysis model (Yates, Analyzing costs, procedures, processes, and outcomes in human services: An introduction, 1996; Yates, 2009). This method entails defining the delivery System; bounding cost parameters; identifying, quantifying, and valuing systemic resource Consumption, and conducting sensitivity analysis of the cost estimates. Results Our analyses estimated both the financial and economic costs of the PROSPER delivery system. Evaluation of PROSPER illustrated how costs vary over time depending on the primacy of certain activities (e.g., team development, facilitator training, program implementation). Additionally, this work describes how the PROSPER model cultivates a complex resource infrastructure and provides preliminary evidence of systemic efficiencies. Conclusions This work highlights the need to study the costs of diffusion across time and broadens definitions of what is essential for successful implementation. In particular, cost analyses offer innovative methodologies for analyzing the resource needs of prevention systems. PMID

  5. Monte Carlo calculations in support of the commissioning of the Northeast Proton Therapy Center.

    PubMed

    Flanz, J; Paganetti, H

    2003-12-01

    Monte Carlo studies were conducted related to the design of the Northeast Proton Therapy Center (NPTC). These studies were also helpful for commissioning the beam delivery performance of the facility. The calculations included preventing proton leakage from the beam delivery nozzle, anomalies in the dose distributions and studies, which could influence future beam delivery techniques. Using simulations it was possible to reduce the proton leakage by over an order of magnitude, while minimizing the weight of the assembly. Interestingly, the thickness of the brass shielding has no influence on the secondary neutron radiation since the number of generated neutrons is almost independent of the amount of brass if the primary beam is completely stopped. Monte Carlo simulations are able to study the effect of small beam misalignments with respect to apertures in the nozzle. Such tolerances are very difficult to define experimentally. Studying the effects of nuclear interactions we showed that, if the dose distributions would be optimized theoretically using the primary proton dose alone, there would be about a 5 % dose increase at the proximal end of a SOBP. In radiobiology studies we found that the RBE at beam entrance increases due to the build-up of the secondary particle fluence.

  6. Reformulation of a clinical-dose system for carbon-ion radiotherapy treatment planning at the National Institute of Radiological Sciences, Japan

    NASA Astrophysics Data System (ADS)

    Inaniwa, Taku; Kanematsu, Nobuyuki; Matsufuji, Naruhiro; Kanai, Tatsuaki; Shirai, Toshiyuki; Noda, Koji; Tsuji, Hiroshi; Kamada, Tadashi; Tsujii, Hirohiko

    2015-04-01

    At the National Institute of Radiological Sciences (NIRS), more than 8,000 patients have been treated for various tumors with carbon-ion (C-ion) radiotherapy in the past 20 years based on a radiobiologically defined clinical-dose system. Through clinical experience, including extensive dose escalation studies, optimum dose-fractionation protocols have been established for respective tumors, which may be considered as the standards in C-ion radiotherapy. Although the therapeutic appropriateness of the clinical-dose system has been widely demonstrated by clinical results, the system incorporates several oversimplifications such as dose-independent relative biological effectiveness (RBE), empirical nuclear fragmentation model, and use of dose-averaged linear energy transfer to represent the spectrum of particles. We took the opportunity to update the clinical-dose system at the time we started clinical treatment with pencil beam scanning, a new beam delivery method, in 2011. The requirements for the updated system were to correct the oversimplifications made in the original system, while harmonizing with the original system to maintain the established dose-fractionation protocols. In the updated system, the radiation quality of the therapeutic C-ion beam was derived with Monte Carlo simulations, and its biological effectiveness was predicted with a theoretical model. We selected the most used C-ion beam with αr = 0.764 Gy-1 and β = 0.0615 Gy-2 as reference radiation for RBE. The C-equivalent biological dose distribution is designed to allow the prescribed survival of tumor cells of the human salivary gland (HSG) in entire spread-out Bragg peak (SOBP) region, with consideration to the dose dependence of the RBE. This C-equivalent biological dose distribution is scaled to a clinical dose distribution to harmonize with our clinical experiences with C-ion radiotherapy. Treatment plans were made with the original and the updated clinical-dose systems, and both

  7. Systems and Components Fuel Delivery System, Water Delivery System, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Systems and Components - Fuel Delivery System, Water Delivery System, Derrick Crane System, and Crane System Details - Marshall Space Flight Center, F-1 Engine Static Test Stand, On Route 565 between Huntsville and Decatur, Huntsville, Madison County, AL

  8. Accurate Quantitative Sensing of Intracellular pH based on Self-ratiometric Upconversion Luminescent Nanoprobe.

    PubMed

    Li, Cuixia; Zuo, Jing; Zhang, Li; Chang, Yulei; Zhang, Youlin; Tu, Langping; Liu, Xiaomin; Xue, Bin; Li, Qiqing; Zhao, Huiying; Zhang, Hong; Kong, Xianggui

    2016-12-09

    Accurate quantitation of intracellular pH (pH i ) is of great importance in revealing the cellular activities and early warning of diseases. A series of fluorescence-based nano-bioprobes composed of different nanoparticles or/and dye pairs have already been developed for pH i sensing. Till now, biological auto-fluorescence background upon UV-Vis excitation and severe photo-bleaching of dyes are the two main factors impeding the accurate quantitative detection of pH i . Herein, we have developed a self-ratiometric luminescence nanoprobe based on förster resonant energy transfer (FRET) for probing pH i , in which pH-sensitive fluorescein isothiocyanate (FITC) and upconversion nanoparticles (UCNPs) were served as energy acceptor and donor, respectively. Under 980 nm excitation, upconversion emission bands at 475 nm and 645 nm of NaYF 4 :Yb 3+ , Tm 3+ UCNPs were used as pH i response and self-ratiometric reference signal, respectively. This direct quantitative sensing approach has circumvented the traditional software-based subsequent processing of images which may lead to relatively large uncertainty of the results. Due to efficient FRET and fluorescence background free, a highly-sensitive and accurate sensing has been achieved, featured by 3.56 per unit change in pH i value 3.0-7.0 with deviation less than 0.43. This approach shall facilitate the researches in pH i related areas and development of the intracellular drug delivery systems.

  9. Accurate Quantitative Sensing of Intracellular pH based on Self-ratiometric Upconversion Luminescent Nanoprobe

    NASA Astrophysics Data System (ADS)

    Li, Cuixia; Zuo, Jing; Zhang, Li; Chang, Yulei; Zhang, Youlin; Tu, Langping; Liu, Xiaomin; Xue, Bin; Li, Qiqing; Zhao, Huiying; Zhang, Hong; Kong, Xianggui

    2016-12-01

    Accurate quantitation of intracellular pH (pHi) is of great importance in revealing the cellular activities and early warning of diseases. A series of fluorescence-based nano-bioprobes composed of different nanoparticles or/and dye pairs have already been developed for pHi sensing. Till now, biological auto-fluorescence background upon UV-Vis excitation and severe photo-bleaching of dyes are the two main factors impeding the accurate quantitative detection of pHi. Herein, we have developed a self-ratiometric luminescence nanoprobe based on förster resonant energy transfer (FRET) for probing pHi, in which pH-sensitive fluorescein isothiocyanate (FITC) and upconversion nanoparticles (UCNPs) were served as energy acceptor and donor, respectively. Under 980 nm excitation, upconversion emission bands at 475 nm and 645 nm of NaYF4:Yb3+, Tm3+ UCNPs were used as pHi response and self-ratiometric reference signal, respectively. This direct quantitative sensing approach has circumvented the traditional software-based subsequent processing of images which may lead to relatively large uncertainty of the results. Due to efficient FRET and fluorescence background free, a highly-sensitive and accurate sensing has been achieved, featured by 3.56 per unit change in pHi value 3.0-7.0 with deviation less than 0.43. This approach shall facilitate the researches in pHi related areas and development of the intracellular drug delivery systems.

  10. A novel misoprostol delivery system for induction of labor: clinical utility and patient considerations.

    PubMed

    Stephenson, Megan L; Wing, Deborah A

    2015-01-01

    Induction of labor is one of the most commonly performed obstetric procedures and will likely become more common as the reproductive population in developed nations changes. As the proportion of women undergoing induction grows, there is a constant search for more efficacious ways to induce labor while maintaining fetal and maternal safety as well as patient satisfaction. With almost half of induced labors requiring cervical ripening, methods for achieving active labor and vaginal delivery are constantly being investigated. Prostaglandins have been shown to be effective induction agents, and specifically vaginal misoprostol, used off-label, have been widely utilized to initiate cervical ripening and active labor. The challenge is to administer this medication accurately while maintaining the ability to discontinue the medication when needed. The misoprostol vaginal insert initiates cervical ripening utilizing a delivery system that controls medication release and can be rapidly removed. This paper reviews the design, development, and clinical utility of the misoprostol vaginal insert for induction of labor as well as patient considerations related to the delivery system.

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

    Schnell, E; Ferreira, C; Ahmad, S

    Purpose: Accuracy of a RSP-HU calibration curve produced for proton treatment planning is tested by comparing the treatment planning system dose grid to physical doses delivered on film by a Mevion S250 double-scattering proton unit. Methods: A single batch of EBT3 Gafchromic film was used for calibration and measurements. The film calibration curve was obtained using Mevion proton beam reference option 20 (15cm range, 10cm modulation). Paired films were positioned at the center of the spread out Bragg peak (SOBP) in solid water. The calibration doses were verified with an ion chamber, including background and doses from 20cGy to 350cGy.more » Films were scanned in a flatbed Epson-Expression 10000-XL scanner, and analyzed using the red channel. A Rando phantom was scanned with a GE LightSpeed CT Simulator. A single-field proton plan (Eclipse, Varian) was calculated to deliver 171cGy to the pelvis section (heterogeneous region), using a standard 4×4cm aperture without compensator, 7.89cm beam range, and 5.36cm SOBP. Varied depths of the calculated distal 90% isodose-line were recorded and compared. The dose distribution from film irradiated between Rando slices was compared with the calculated plans using RIT v.6.2. Results: Distal 90% isodose-line depth variation between CT scans was 2mm on average, and 4mm at maximum. Fine calculation of this variation was restricted by the dose calculation grid, as well as the slice thickness. Dose differences between calibrated film measurements and calculated doses were on average 5.93cGy (3.5%), with the large majority of differences forming a normal distribution around 3.5cGy (2%). Calculated doses were almost entirely greater than those measured. Conclusion: RSP to HU calibration curve is shown to produce distal depth variation within the margin of tolerance (±4.3mm) across all potential scan energies and protocols. Dose distribution calculation is accurate to 2–4% within the SOBP, including areas of high tissue

  12. Integrated delivery systems focus on service delivery after capitation efforts stall.

    PubMed

    2005-03-01

    Integrated delivery systems focus on service delivery after capitation efforts stall. Integrated delivery systems are going through changes that are focusing the provider organizations more on delivering care than managing risk, says Dean C. Coddington, one of the leading researchers into capitated organizations and a senior consultant with McManis Consulting in Denver.

  13. Impact of Absorption and Transport on Intelligent Therapeutics and Nano-scale Delivery of Protein Therapeutic Agents

    PubMed Central

    Peppas, Nicholas A.; Carr, Daniel A

    2009-01-01

    The combination of materials design and advances in nanotechnology has led to the development of new therapeutic protein delivery systems. The pulmonary, nasal, buccal and other routes have been investigated as delivery options for protein therapy, but none result in improved patient compliances and patient quality of life as the oral route. For the oral administration of these new systems, an understanding of protein transport is essential because of the dynamic nature of the gastrointestinal tract and the barriers to transport that exist. Models have been developed to describe the transport between the gastrointestinal lumen and the bloodstream, and laboratory techniques like cell culture provide a means to investigate the absorption and transport of many therapeutic agents. Biomaterials, including stimuli-sensitive complexation hydrogels, have been investigated as promising carriers for oral delivery. However, the need to develop models that accurately predict protein blood concentration as a function of the material structure and properties still exists. PMID:20161384

  14. Planning and delivery of four-dimensional radiation therapy with multileaf collimators

    NASA Astrophysics Data System (ADS)

    McMahon, Ryan L.

    This study is an investigation of the application of multileaf collimators (MLCs) to the treatment of moving anatomy with external beam radiation therapy. First, a method for delivering intensity modulated radiation therapy (IMRT) to moving tumors is presented. This method uses an MLC control algorithm that calculates appropriate MLC leaf speeds in response to feedback from real-time imaging. The algorithm does not require a priori knowledge of a tumor's motion, and is based on the concept of self-correcting DMLC leaf trajectories . This gives the algorithm the distinct advantage of allowing for correction of DMLC delivery errors without interrupting delivery. The algorithm is first tested for the case of one-dimensional (1D) rigid tumor motion in the beam's eye view (BEV). For this type of motion, it is shown that the real-time tracking algorithm results in more accurate deliveries, with respect to delivered intensity, than those which ignore motion altogether. This is followed by an appropriate extension of the algorithm to two-dimensional (2D) rigid motion in the BEV. For this type of motion, it is shown that the 2D real-time tracking algorithm results in improved accuracy (in the delivered intensity) in comparison to deliveries which ignore tumor motion or only account for tumor motion which is aligned with MLC leaf travel. Finally, a method is presented for designing DMLC leaf trajectories which deliver a specified intensity over a moving tumor without overexposing critical structures which exhibit motion patterns that differ from that of the tumor. In addition to avoiding overexposure of critical organs, the method can, in the case shown, produce deliveries that are superior to anything achievable using stationary anatomy. In this regard, the method represents a systematic way to include anatomical motion as a degree of freedom in the optimization of IMRT while producing treatment plans that are deliverable with currently available technology. These results

  15. Poster — Thur Eve — 45: Comparison of different Monte Carlo methods of scoring linear energy transfer in modulated proton therapy beams

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

    Granville, DA; Sawakuchi, GO

    2014-08-15

    In this work, we demonstrate inconsistencies in commonly used Monte Carlo methods of scoring linear energy transfer (LET) in proton therapy beams. In particle therapy beams, the LET is an important parameter because the relative biological effectiveness (RBE) depends on it. LET is often determined using Monte Carlo techniques. We used a realistic Monte Carlo model of a proton therapy nozzle to score proton LET in spread-out Bragg peak (SOBP) depth-dose distributions. We used three different scoring and calculation techniques to determine average LET at varying depths within a 140 MeV beam with a 4 cm SOBP and a 250more » MeV beam with a 10 cm SOBP. These techniques included fluence-weighted (Φ-LET) and dose-weighted average (D-LET) LET calculations from: 1) scored energy spectra converted to LET spectra through a lookup table, 2) directly scored LET spectra and 3) accumulated LET scored ‘on-the-fly’ during simulations. All protons (primary and secondary) were included in the scoring. Φ-LET was found to be less sensitive to changes in scoring technique than D-LET. In addition, the spectral scoring methods were sensitive to low-energy (high-LET) cutoff values in the averaging. Using cutoff parameters chosen carefully for consistency between techniques, we found variations in Φ-LET values of up to 1.6% and variations in D-LET values of up to 11.2% for the same irradiation conditions, depending on the method used to score LET. Variations were largest near the end of the SOBP, where the LET and energy spectra are broader.« less

  16. Improved overall delivery documentation following implementation of a standardized shoulder dystocia delivery form

    PubMed Central

    Moragianni, Vasiliki A.; Hacker, Michele R.; Craparo, Frank J.

    2013-01-01

    Objective Our objective was to evaluate whether using a standardized shoulder dystocia delivery form improved documentation. A standardized delivery form was added to our institution’s obstetrical record in August 2003. Methods A retrospective cohort study was conducted comparing 100 vaginal deliveries complicated by shoulder dystocia before, and 81 after implementation of the standardized delivery form. The two groups were compared in terms of obstetric characteristics, neonatal outcomes and documentation components. Results Charts that included the standardized delivery form were more likely to contain documentation of estimated fetal weight (82.7% vs. 39.0% without the form, P<0.001) and head-to-shoulder delivery interval (76.5% vs. 15.0% without the form, P<0.001). Both groups were statistically similar in terms of documenting estimated blood loss and fetal weight, umbilical cord pH, type and order of maneuvers utilized to relieve the shoulder dystocia, and second stage duration. Conclusions Inclusion of a standardized form in the delivery record improves the rate of documentation of both shoulder dystocia-specific and general delivery components. PMID:22017330

  17. Building a polysaccharide hydrogel capsule delivery system for control release of ibuprofen.

    PubMed

    Chen, Zhi; Wang, Ting; Yan, Qing

    2018-02-01

    Development of a delivery system which can effectively carry hydrophobic drugs and have pH response is becoming necessary. Here we demonstrate that through preparation of β-cyclodextrin polymer (β-CDP), a hydrophobic drug molecule of ibuprofen (IBU) was incorporated into our prepared β-CDP inner cavities, aiming to improve the poor water solubility of IBU. A core-shell capsule structure has been designed for achieving the drug pH targeted and sustained release. This delivery system was built with polysaccharide polymer of Sodium alginate (SA), sodium carboxymethylcellulose (CMC) and hydroxyethyl cellulose (HEC) by physical cross-linking. The drug pH-response control release is this hydrogel system's chief merit, which has potential value for synthesizing enteric capsule. Besides, due to our simple preparing strategy, optimal conditions can be readily determined and the synthesis process can be accurately controlled, leading to consistent and reproducible hydrogel capsules. In addition, phase-solubility method was used to investigate the solubilization effect of IBU by β-CDP. SEM was used to prove the forming of core and shell structure. FT-IR and 1 H-NMR were also used to perform structural characteristics. By the technique of UV determination, the pH targeted and sustained release study were also performed. The results have proved that our prepared polysaccharide hydrogel capsule delivery system has potential applications as oral drugs delivery in the field of biomedical materials.

  18. Colloidal drug delivery system: amplify the ocular delivery.

    PubMed

    Ali, Javed; Fazil, Mohd; Qumbar, Mohd; Khan, Nazia; Ali, Asgar

    2016-01-01

    The ocular perceivers are the most voluntarily accessible organs in terms of location in the body, yet drug distribution to these tissues is one of the most intriguing and challenging endeavors and problematic to the pharmaceutical scientist. The most of ocular diseases are treated with topical application of conventional formulation, i.e. solutions, suspensions and ointment. Typically on installation of these conventional formulations, only <5% of the applied dose penetrates the cornea and reaches intraocular tissues, while a major fraction of the instilled dose is wastage due to the presence of many ocular barriers like external barriers, rapid loss of the instilled solution from the precorneal area and nasolacrimal drainage system. Systemic absorption caused systemic side effects varying from mild to life-threatening events. The main objective of this review is to explore the role of colloidal delivery of drug to minimize the drawbacks associated with them. This review provides an insight into the various constraints associated with ocular drug delivery, summarizes recent findings and applications of colloidal delivery systems, i.e. nanoparticles, nanosuspensions, liposomes, niosomes, dendrimers and contact lenses containing nanoparticles have the capacity to distribute ocular drugs to categorical target sites and hold promise to revolutionize the therapy of many ocular perceiver diseases and minimized the circumscription of conventional delivery. Form the basis of literature review, it has been found that the novel delivery system have greater impact to maximize ocular drug absorption, and minimize systemic absorption and side effects.

  19. Investigation of microbubble response to long pulses used in ultrasound-enhanced drug delivery.

    PubMed

    Mannaris, Christophoros; Averkiou, Michalakis A

    2012-04-01

    In current drug delivery approaches, microbubbles and drugs can be co-administered while ultrasound is applied. The mechanism of microbubble interaction with ultrasound, the drug and the cells is not fully understood. The aim of this study was to investigate microbubble response to long ultrasonic pulses used in drug delivery approaches. Two different in vitro set-ups were considered: with the microbubbles diluted in an enclosure and with the microbubbles flowing in a capillary tube. Acoustic streaming, which influences the observed bubble response, was observed in "typical" drug delivery conditions in the first set-up. With the capillary set-up, streaming effects were avoided and accurate bubble responses were recorded. The diffraction pattern of the source greatly influences the bubble response and in different locations of the field different bubble responses are observed. At low nondestructive pressures, microbubbles can oscillate for thousands of cycles repeatedly. At high acoustic pressures (at 1 MHz), most bubble activity disappeared within about 100 μs despite the length of the pulse, mainly due to violent bubble destruction and subsequent accelerated diffusion. Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  20. 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

  1. The U.S. Twin Delivery Volume and Association with Cesarean Delivery Rates: A Hospital-Level Analysis.

    PubMed

    Easter, Sarah Rae; Robinson, Julian N; Carusi, Daniela; Little, Sarah E

    2018-03-01

     The objective of this study was to test whether hospitals experienced in twin delivery have lower rates of cesarean delivery for twins.  We divided obstetric hospitals in the 2011 National Inpatient Sample by quartile of annual twin deliveries and compared twin cesarean delivery rates between hospitals with weighted linear regression. We used Pearson's coefficients to correlate a hospital's twin cesarean delivery rate to its overall cesarean delivery and vaginal birth after cesarean (VBAC) rates.  Annual twin delivery volume ranged from 1 to 506 across the 547 analyzed hospitals with a median of 10 and mode of 3. Adjusted rates of cesarean delivery were independent of delivery volume with a rate of 75.5 versus 74.8% in the lowest and highest volume hospitals ( p  = 0.09 across quartiles). A hospital's cesarean delivery rate for twins moderately correlated with the overall cesarean rate ( r  = 0.52, p  < 0.01) and inversely correlated with VBAC rate ( r  =  - 0.42, p  < 0.01).  Most U.S. obstetrical units perform a low volume of twin deliveries with no decrease in cesarean delivery rates at higher volume hospitals. Twin cesarean delivery rates correlate with other obstetric parameters such as singleton cesarean delivery and VBAC rates suggesting twin cesarean delivery rate is more closely related to a hospital's general obstetric practice than its twin delivery volume. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  2. Comparison of outcomes between operative vaginal deliveries and spontaneous vaginal deliveries in southeast Nigeria.

    PubMed

    Lawani, Lucky O; Anozie, Okechukwu B; Ezeonu, Paul O; Iyoke, Chukwuemeka A

    2014-06-01

    To evaluate the incidence of, indications for, and outcome of operative vaginal deliveries compared with spontaneous vaginal deliveries in southeast Nigeria. A retrospective cohort study was conducted involving cases of operative vaginal delivery performed at Ebonyi State University Teaching Hospital over a 10-year period. Data on the procedures were abstracted from the operation notes of the medical records of parturients. An incidence of 4.7% (n = 461) was recorded. The most common indications for vacuum and forceps delivery were prolonged second stage of labor (44.9%) and poor maternal effort (27.8%). The only indication for destructive operation was intrauterine fetal death (3.7%). The risk ratio (RR) for hemorrhage/vulvar hematoma was 1.14 (95% confidence interval [CI], 0.53-2.48) for vacuum-assisted delivery and 5.49 (95% CI, 0.82-36.64) for forceps delivery. The RR for genital laceration was 1.21 (95% CI, 0.44-3.30) for vacuum-assisted delivery and 9.41 (95% CI, 1.33-66.65) for forceps delivery. The risk of fetal scalp bruises and caput succedaneum was higher for operative vaginal delivery than for spontaneous vaginal delivery, with no significant difference in maternal morbidity. The perinatal mortality rate was 0.9 per 1000 live births. Operative vaginal delivery by experienced healthcare providers is associated with good obstetric outcomes with minimal risk. Copyright © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  3. Simulation study of electric-guided delivery of 0.4µm monodisperse and polydisperse aerosols to the ostiomeatal complex.

    PubMed

    Xi, Jinxiang; Yuan, Jiayao Eddie; Si, Xiuhua April

    2016-05-01

    Despite the high prevalence of rhinosinusitis, current inhalation therapy shows limited efficacy due to extremely low drug delivery efficiency to the paranasal sinuses. Novel intranasal delivery systems are needed to enhance targeted delivery to the sinus with therapeutic dosages. An optimization framework for intranasal drug delivery was developed to target polydisperse charged aerosols to the ostiomeatal complex (OMC) with electric guidance. The delivery efficiency of a group of charged aerosols recently reported in the literature was numerically assessed and optimized in an anatomically accurate nose-sinus model. Key design variables included particle charge number, particle size and distribution, electrode strength, and inhalation velocity. Both monodisperse and polydisperse aerosol profiles were considered. Results showed that the OMC delivery efficiency was highly sensitive to the applied electric field and electrostatic charges carried by the particles. Through the synthesis of electric-guidance and point drug release, focused deposition with significantly enhanced dosage in the OMC can be achieved. For 0.4 µm charged aerosols, an OMC delivery efficiency of 51.6% was predicted for monodisperse aerosols and 34.4% for polydisperse aerosols. This difference suggested that the aerosol profile exerted a notable effect on intranasal deliveries. Sensitivity analysis indicated that the OMC deposition fraction was highly sensitive to the charge and size of particles and was less sensitive to the inhalation velocity considered in this study. Experimental studies are needed to validate the numerically optimized designs. Further studies are warranted to investigate the targeted OMC delivery with both electric and acoustics controls, the latter of which has the potential to further deliver the drug particles into the sinus cavity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. A Novel Methodology for Applying Multivoxel MR Spectroscopy to Evaluate Convection-Enhanced Drug Delivery in Diffuse Intrinsic Pontine Gliomas.

    PubMed

    Guisado, D I; Singh, R; Minkowitz, S; Zhou, Z; Haque, S; Peck, K K; Young, R J; Tsiouris, A J; Souweidane, M M; Thakur, S B

    2016-07-01

    Diffuse intrinsic pontine gliomas are inoperable high-grade gliomas with a median survival of less than 1 year. Convection-enhanced delivery is a promising local drug-delivery technique that can bypass the BBB in diffuse intrinsic pontine glioma treatment. Evaluating tumor response is critical in the assessment of convection-enhanced delivery of treatment. We proposed to determine the potential of 3D multivoxel (1)H-MR spectroscopy to evaluate convection-enhanced delivery treatment effect in these tumors. We prospectively analyzed 3D multivoxel (1)H-MR spectroscopy data for 6 patients with nonprogressive diffuse intrinsic pontine gliomas who received convection-enhanced delivery treatment of a therapeutic antibody (Phase I clinical trial NCT01502917). To compare changes in the metabolite ratios with time, we tracked the metabolite ratios Cho/Cr and Cho/NAA at several ROIs: normal white matter, tumor within the convection-enhanced delivery infusion site, tumor outside of the infused area, and the tumor average. There was a comparative decrease in both Cho/Cr and Cho/NAA metabolite ratios at the tumor convection-enhanced delivery site versus tumor outside the infused area. We used MR spectroscopy voxels with dominant white matter as a reference. The difference between changes in metabolite ratios became more prominent with increasing time after convection-enhanced delivery treatment. The comparative change in metabolite ratios between the convection-enhanced delivery site and the tumor site outside the infused area suggests that multivoxel (1)H-MR spectroscopy, in combination with other imaging modalities, may provide a clinical tool to accurately evaluate local tumor response after convection-enhanced delivery treatment. © 2016 by American Journal of Neuroradiology.

  5. The development of a novel cricket bowling system: recreating spin and swing bowling deliveries at the elite level

    NASA Astrophysics Data System (ADS)

    West, A. A.; Justham, L.

    2008-03-01

    During the game of cricket, bowlers create different deliveries by altering the manner in which they release the ball from their hand. The orientation of the seam, the speed at which the ball is released and the magnitude and direction of the spin combine to determine the motion of the ball through the air and its movement after impact with the wicket. These factors have to be considered if automatic training machines are to be capable of replicating elite bowling deliveries. The need for automotive systems for batting and fielding training at the elite level has arisen due to: (i) the capabilities of human bowlers are limited by the onset of fatigue and the risk of injury and (ii) a large number of accurate and repeatable deliveries to be ''programmable'' by coaches to ensure batsmen and fielders are tested to the limits of their abilities and a training benefit is achieved.

  6. Levodopa delivery systems: advancements in delivery of the gold standard.

    PubMed

    Ngwuluka, Ndidi; Pillay, Viness; Du Toit, Lisa C; Ndesendo, Valence; Choonara, Yahya; Modi, Girish; Naidoo, Dinesh

    2010-02-01

    Despite the fact that Parkinson's disease (PD) was discovered almost 200 years ago, its treatment and management remain immense challenges because progressive loss of dopaminergic nigral neurons, motor complications experienced by the patients as the disease progresses and drawbacks of pharmacotherapeutic management still persist. Various therapeutic agents have been used in the management of PD, including levodopa (l-DOPA), selegiline, amantadine, bromocriptine, entacapone, pramipexole dihydrochloride and more recently istradefylline and rasagiline. Of all agents, l-DOPA although the oldest, remains the most effective. l-DOPA is easier to administer, better tolerated, less expensive and is required by almost all PD patients. However, l-DOPA's efficacy in advanced PD is significantly reduced due to metabolism, subsequent low bioavailability and irregular fluctuations in its plasma levels. Significant strides have been made to improve the delivery of l-DOPA in order to enhance its bioavailability and reduce plasma fluctuations as well as motor complications experienced by patients purportedly resulting from pulsatile stimulation of the striatal dopamine receptors. Drug delivery systems that have been instituted for the delivery of l-DOPA include immediate release formulations, liquid formulations, dispersible tablets, controlled release formulations, dual-release formulations, microspheres, infusion and transdermal delivery, among others. In this review, the l-DOPA-loaded drug delivery systems developed over the past three decades are elaborated. The ultimate aim was to assess critically the attempts made thus far directed at improving l-DOPA absorption, bioavailability and maintenance of constant plasma concentrations, including the drug delivery technologies implicated. This review highlights the fact that neuropharmaceutics is at a precipice, which is expected to spur investigators to take that leap to enable the generation of innovative delivery systems for the

  7. Rumen-stable delivery systems.

    PubMed

    Papas; Wu

    1997-12-08

    Ruminants have a distinct digestive system which serves a unique symbiotic relationship between the host animal and predominantly anaerobic rumen bacteria and protozoa. Rumen fermentation can be both beneficial by enabling utilization of cellulose and non-protein nitrogen and detrimental by reducing the nutritive value of some carbohydrates, high biological value proteins and by hydrogenating unsaturated lipids. In addition it can also result in the modification and inactivation of many pharmacologically active ingredients administered to the host animal via the oral route. The advances in ruminant nutrition and health demand a rumen-stable delivery system which can deliver the active ingredient post-ruminally while simultaneously meet efficacy, safety and cost criteria. In contrast to drug delivery systems for humans, the demand for low-cost has hindered the development of effective rumen-stable delivery systems. Historically, heat and chemical treatment of feed components, low solubility analogues or lipid-based formulations have been used to achieve some degree of rumen-stability, and products have been developed accordingly. Recently, a polymeric pH-dependent rumen-stable delivery system has been developed and commercialized. The rationale of this delivery system is based on the pH difference between ruminal and abomasal fluids. The delivery system is composed of a basic polymer, a hydrophobic substance and a pigment material. It can be applied as a coating to solid particles via a common encapsulation method such as air-suspension coating. In the future, the delivery system could be used to deliver micronutrients and pharmaceuticals post-ruminally to ruminant animals. A further possible application of the delivery system is that it could also be combined with other controlled delivery devices/systems in order to enhance slow release or to achieve targeted delivery needs for ruminants. This paper discusses the rumen protection and the abomasal release mechanism

  8. MRI in ocular drug delivery

    PubMed Central

    Li, S. Kevin; Lizak, Martin J.; Jeong, Eun-Kee

    2008-01-01

    Conventional pharmacokinetic methods for studying ocular drug delivery are invasive and cannot be conveniently applied to humans. The advancement of MRI technology has provided new opportunities in ocular drug-delivery research. MRI provides a means to non-invasively and continuously monitor ocular drug-delivery systems with a contrast agent or compound labeled with a contrast agent. It is a useful technique in pharmacokinetic studies, evaluation of drug-delivery methods, and drug-delivery device testing. Although the current status of the technology presents some major challenges to pharmaceutical research using MRI, it has a lot of potential. In the past decade, MRI has been used to examine ocular drug delivery via the subconjunctival route, intravitreal injection, intrascleral injection to the suprachoroidal space, episcleral and intravitreal implants, periocular injections, and ocular iontophoresis. In this review, the advantages and limitations of MRI in the study of ocular drug delivery are discussed. Different MR contrast agents and MRI techniques for ocular drug-delivery research are compared. Ocular drug-delivery studies using MRI are reviewed. PMID:18186077

  9. Association between vaginal birth after cesarean delivery and primary cesarean delivery rates.

    PubMed

    Rosenstein, Melissa G; Kuppermann, Miriam; Gregorich, Steven E; Cottrell, Erika K; Caughey, Aaron B; Cheng, Yvonne W

    2013-11-01

    To estimate the association between vaginal birth after cesarean delivery (VBAC) rates and primary cesarean delivery rates in California hospitals. Hospital VBAC rates were calculated using birth certificate and discharge data from 2009, and hospitals were categorized by quartile of VBAC rate. Multivariable logistic regression analysis was performed to estimate the odds of cesarean delivery among low-risk nulliparous women with singleton pregnancies at term in vertex presentation (nulliparous term singleton vertex) by hospital VBAC quartile while controlling for many patient-level and hospital-level confounders. There were 468,789 term singleton births in California in 2009 at 255 hospitals, 125,471 of which were low-risk nulliparous term singleton vertex. Vaginal birth after cesarean delivery rates varied between hospitals, with a range of 0-44.6%. Rates of cesarean delivery among low-risk nulliparous term singleton vertex women declined significantly with increasing VBAC rate. When adjusted for maternal and hospital characteristics, low-risk nulliparous term singleton vertex women who gave birth in hospitals in the highest VBAC quartile had an odds ratio of 0.55 (95% confidence interval 0.46-0.66) of cesarean delivery compared with women at hospitals with the lowest VBAC rates. Each percentage point increase in a hospital's VBAC rate was associated with a 0.65% decrease in the low-risk nulliparous term singleton vertex cesarean delivery rate. Hospitals with higher rates of VBAC have lower rates of primary cesarean delivery among low-risk nulliparous women with singleton pregnancies at term in vertex presentation. II.

  10. Comparison of CRP and ALK-P serum levels in prediction of preterm delivery

    PubMed Central

    Shahshahan, Zahra; Iravani, Hoda

    2016-01-01

    Background: Preterm birth, defined as birth occurring before 37 weeks of gestation, is a common complication of pregnancy and may lead to death or long-term disability in newborns. Accurate diagnosis is, therefore, crucial for identifying those women undergoing preterm labor who are at greatest risk of preterm delivery. This may allow transport to a regional obstetrical center and permit time for corticosteroid therapy. Recent study recommends several markers such as CRP (C-reactive protein) and ALK-P (alkaline phosphatase) to predict preterm delivery. Materials and Methods: We select a total of 300 pregnant women that had symptoms of premature birth. All of them were under treatment with tocolytic and serum sample were taken to assess the level of CRP-ALKp. Cervix length and the time of response to tocolytic were measured. 110 pregnant of them had preterm labor. 110 patient that had a term labor selected as a control group. Results: Qualitative evaluation of efficacy CRP level on preterm delivery showed a significant relationship with 27 as a cut of point of CRP (P < 0.00001 –OR = 7.5). Investigate of effect of ALK-P level on preterm delivery refers to a significant relationship with 399 as a cut of point of ALKP (P < 0.00001 –OR = 5). Inquire of efficacy of CRP level and ALK-P level on preterm delivery demonstrate a significant relationship (P < 0.0001 1OR = 9). Conclusions: Maternal concentrations of CRP and ALKP and cervix length can be used as appropriate biomarker for predicting preterm labor and response to tocolytic therapy in pregnant women. PMID:26962519

  11. NNLOPS accurate associated HW production

    NASA Astrophysics Data System (ADS)

    Astill, William; Bizon, Wojciech; Re, Emanuele; Zanderighi, Giulia

    2016-06-01

    We present a next-to-next-to-leading order accurate description of associated HW production consistently matched to a parton shower. The method is based on reweighting events obtained with the HW plus one jet NLO accurate calculation implemented in POWHEG, extended with the MiNLO procedure, to reproduce NNLO accurate Born distributions. Since the Born kinematics is more complex than the cases treated before, we use a parametrization of the Collins-Soper angles to reduce the number of variables required for the reweighting. We present phenomenological results at 13 TeV, with cuts suggested by the Higgs Cross section Working Group.

  12. Lifetime increased cancer risk in mice following exposure to clinical proton beam generated neutrons

    PubMed Central

    Gerweck, Leo E.; Huang, Peigen; Lu, Hsiao-Ming; Paganetti, Harald; Zhou, Yenong

    2014-01-01

    Purpose To evaluate the lifespan and risk of cancer following whole-body exposure of mice to neutrons generated by a passively scattered clinical SOBP proton beam. Methods and Materials Three hundred young adult female FVB/N mice, 152 test and 148 control, were entered into the experiment. Mice were placed in an annular cassette around a cylindrical phantom, which was positioned lateral to the mid SOBP of a 165 MeV, clinical proton beam. The average distance from the edge of the mid SOBP to the conscious active mice was 21.5 cm. The phantom was irradiated with once daily fractions of 25 Gy, 4 days per week, for 6 weeks. The age at death and cause of death, i.e., cancer and type vs. non-cancer causes, were assessed over the lifespan of the mice. Results Exposure of mice to a dose of 600 Gy of proton beam generated neutrons, reduced the median lifespan of the mice by 4.2% (Kaplan-Meier cumulative survival, P = 0.053). The relative risk of death from cancer in neutron exposed vs. control mice was 1.40 for cancer of all types (P = 0.0006) and 1.22 for solid cancers (P = 0.09). For a typical 60 Gy dose of clinical protons, the observed 22% increased risk of solid cancer would be expected to decrease by a factor of 10. Conclusions Exposure of mice to neutrons generated by a proton dose which exceeds a typical course of radiotherapy by a factor of 10, resulted in a statistically significant increase in the background incidence of leukemia and a marginally significant increase in solid cancer. The results indicate that the risk of out-of-field 2nd solid cancers from SOBP proton generated neutrons and typical treatment schedules, is 6 - 10 times less than is suggested by current neutron risk estimates. PMID:24725699

  13. Assisted Vaginal Delivery

    MedlinePlus

    ... Patient Education FAQs Assisted Vaginal Delivery Patient Education Pamphlets - Spanish Assisted Vaginal Delivery FAQ192, February 2016 PDF ... on Patient Safety For Patients Patient FAQs Spanish Pamphlets Teen Health About ACOG About Us Leadership & Governance ...

  14. Stimuli-Responsive Polymeric Systems for Controlled Protein and Peptide Delivery: Future Implications for Ocular Delivery.

    PubMed

    Mahlumba, Pakama; Choonara, Yahya E; Kumar, Pradeep; du Toit, Lisa C; Pillay, Viness

    2016-07-30

    Therapeutic proteins and peptides have become notable in the drug delivery arena for their compatibility with the human body as well as their high potency. However, their biocompatibility and high potency does not negate the existence of challenges resulting from physicochemical properties of proteins and peptides, including large size, short half-life, capability to provoke immune responses and susceptibility to degradation. Various delivery routes and delivery systems have been utilized to improve bioavailability, patient acceptability and reduce biodegradation. The ocular route remains of great interest, particularly for responsive delivery of macromolecules due to the anatomy and physiology of the eye that makes it a sensitive and complex environment. Research in this field is slowly gaining attention as this could be the breakthrough in ocular drug delivery of macromolecules. This work reviews stimuli-responsive polymeric delivery systems, their use in the delivery of therapeutic proteins and peptides as well as examples of proteins and peptides used in the treatment of ocular disorders. Stimuli reviewed include pH, temperature, enzymes, light, ultrasound and magnetic field. In addition, it discusses the current progress in responsive ocular drug delivery. Furthermore, it explores future prospects in the use of stimuli-responsive polymers for ocular delivery of proteins and peptides. Stimuli-responsive polymers offer great potential in improving the delivery of ocular therapeutics, therefore there is a need to consider them in order to guarantee a local, sustained and ideal delivery of ocular proteins and peptides, evading tissue invasion and systemic side-effects.

  15. Accurate Arabic Script Language/Dialect Classification

    DTIC Science & Technology

    2014-01-01

    Army Research Laboratory Accurate Arabic Script Language/Dialect Classification by Stephen C. Tratz ARL-TR-6761 January 2014 Approved for public...1197 ARL-TR-6761 January 2014 Accurate Arabic Script Language/Dialect Classification Stephen C. Tratz Computational and Information Sciences...Include area code) Standard Form 298 (Rev. 8/98) Prescribed by ANSI Std. Z39.18 January 2014 Final Accurate Arabic Script Language/Dialect Classification

  16. Cell-Mediated Drugs Delivery

    PubMed Central

    Batrakova, Elena V.; Gendelman, Howard E.; Kabanov, Alexander V.

    2011-01-01

    INTRODUCTION Drug targeting to sites of tissue injury, tumor or infection with limited toxicity is the goal for successful pharmaceutics. Immunocytes (including mononuclear phagocytes (dendritic cells, monocytes and macrophages), neutrophils, and lymphocytes) are highly mobile; they can migrate across impermeable barriers and release their drug cargo at sites of infection or tissue injury. Thus immune cells can be exploited as trojan horses for drug delivery. AREAS COVERED IN THIS REVIEW This paper reviews how immunocytes laden with drugs can cross the blood brain or blood tumor barriers, to facilitate treatments for infectious diseases, injury, cancer, or inflammatory diseases. The promises and perils of cell-mediated drug delivery are reviewed, with examples of how immunocytes can be harnessed to improve therapeutic end points. EXPERT OPINION Using cells as delivery vehicles enables targeted drug transport, and prolonged circulation times, along with reductions in cell and tissue toxicities. Such systems for drug carriage and targeted release represent a novel disease combating strategy being applied to a spectrum of human disorders. The design of nanocarriers for cell-mediated drug delivery may differ from those used for conventional drug delivery systems; nevertheless, engaging different defense mechanisms into drug delivery may open new perspectives for the active delivery of drugs. PMID:21348773

  17. Controlled Drug Delivery Using Microdevices

    PubMed Central

    Sanjay, Sharma T.; Dou, Maowei; Fu, Guanglei; Xu, Feng; Li, XiuJun

    2016-01-01

    Therapeutic drugs administered systematically are evenly distributed to the whole body through blood circulation and have to cross many biological barriers before reaching the pathological site. Conventional drug delivery may make drugs inactive or reduce their potency as they may be hydrolyzed or degraded enzymatically and are rapidly excreted through the urinary system resulting in suboptimal concentration of drugs at the desired site. Controlled drug delivery aims to localize the pharmacological activity of the drug to the desired site at desired release rates. The advances made by micro/nanofluidic technologies have provided new opportunities for better-controlled drug delivery. Various components of a drug delivery system can be integrated within a single tiny micro/nanofluidic chip. This article reviews recent advances of controlled drug delivery made by microfluidic/nanofluidic technologies. We first discuss microreservoir-based drug delivery systems. Then we highlight different kinds of microneedles used for controlled drug delivery, followed with a brief discussion about the current limitations and the future prospects of controlled drug delivery systems. PMID:26813304

  18. Controlled Drug Delivery Using Microdevices.

    PubMed

    Sanjay, Sharma T; Dou, Maowei; Fu, Guanglei; Xu, Feng; Li, XiuJun

    Therapeutic drugs administered systematically are evenly distributed to the whole body through blood circulation and have to cross many biological barriers before reaching the pathological site. Conventional drug delivery may make drugs inactive or reduce their potency as they may be hydrolyzed or degraded enzymatically and are rapidly excreted through the urinary system resulting in suboptimal concentration of drugs at the desired site. Controlled drug delivery aims to localize the pharmacological activity of the drug to the desired site at desired release rates. The advances made by micro/nanofluidic technologies have provided new opportunities for better-controlled drug delivery. Various components of a drug delivery system can be integrated within a single tiny micro/nanofluidic chip. This article reviews recent advances of controlled drug delivery made by microfluidic/nanofluidic technologies. We first discuss microreservoir-based drug delivery systems. Then we highlight different kinds of microneedles used for controlled drug delivery, followed with a brief discussion about the current limitations and the future prospects of controlled drug delivery systems.

  19. Method to make accurate concentration and isotopic measurements for small gas samples

    NASA Astrophysics Data System (ADS)

    Palmer, M. R.; Wahl, E.; Cunningham, K. L.

    2013-12-01

    Carbon isotopic ratio measurements of CO2 and CH4 provide valuable insight into carbon cycle processes. However, many of these studies, like soil gas, soil flux, and water head space experiments, provide very small gas sample volumes, too small for direct measurement by current constant-flow Cavity Ring-Down (CRDS) isotopic analyzers. Previously, we addressed this issue by developing a sample introduction module which enabled the isotopic ratio measurement of 40ml samples or smaller. However, the system, called the Small Sample Isotope Module (SSIM), does dilute the sample during the delivery with inert carrier gas which causes a ~5% reduction in concentration. The isotopic ratio measurements are not affected by this small dilution, but researchers are naturally interested accurate concentration measurements. We present the accuracy and precision of a new method of using this delivery module which we call 'double injection.' Two portions of the 40ml of the sample (20ml each) are introduced to the analyzer, the first injection of which flushes out the diluting gas and the second injection is measured. The accuracy of this new method is demonstrated by comparing the concentration and isotopic ratio measurements for a gas sampled directly and that same gas measured through the SSIM. The data show that the CO2 concentration measurements were the same within instrument precision. The isotopic ratio precision (1σ) of repeated measurements was 0.16 permil for CO2 and 1.15 permil for CH4 at ambient concentrations. This new method provides a significant enhancement in the information provided by small samples.

  20. Field-size dependence of doses of therapeutic carbon beams.

    PubMed

    Kusano, Yohsuke; Kanai, Tatsuaki; Yonai, Shunsuke; Komori, Masataka; Ikeda, Noritoshi; Tachikawa, Yuji; Ito, Atsushi; Uchida, Hirohisa

    2007-10-01

    To estimate the physical dose at the center of spread-out Bragg peaks (SOBP) for various conditions of the irradiation system, a semiempirical approach was applied. The dose at the center of the SOBP depends on the field size because of large-angle scattering particles in the water phantom. For a small field of 5 x 5 cm2, the dose was reduced to 99.2%, 97.5%, and 96.5% of the dose used for the open field in the case of 290, 350, and 400 MeV/n carbon beams, respectively. Based on the three-Gaussian form of the lateral dose distributions of the carbon pencil beam, which has previously been shown to be effective for describing scattered carbon beams, we reconstructed the dose distributions of the SOBP beam. The reconstructed lateral dose distribution reproduced the measured lateral dose distributions very well. The field-size dependencies calculated using the reconstructed lateral dose distribution of the therapeutic carbon beam agreed with the measured dose dependency very well. The reconstructed beam was also used for irregularly shaped fields. The resultant dose distribution agreed with the measured dose distribution. The reconstructed beams were found to be applicable to the treatment-planning system.

  1. In vivo radiobiological assessment of the new clinical carbon ion beams at CNAO.

    PubMed

    Facoetti, A; Vischioni, B; Ciocca, M; Ferrarini, M; Furusawa, Y; Mairani, A; Matsumoto, Y; Mirandola, A; Molinelli, S; Uzawa, A; Vilches, Freixas G; Orecchia, R

    2015-09-01

    In this article, the in vivo study performed to evaluate the uniformity of biological doses within an hypothetical target volume and calculate the values of relative biological effectiveness (RBE) at different depths in the spread-out Bragg peak (SOBP) of the new CNAO (National Centre for Oncological Hadrontherapy) carbon beams is presented, in the framework of a typical radiobiological beam calibration procedure. The RBE values (relative to (60)Co γ rays) of the CNAO active scanning carbon ion beams were determined using jejunal crypt regeneration in mice as biological system at the entrance, centre and distal end of a 6-cm SOBP. The RBE values calculated from the iso-effective doses to reduce crypt survival per circumference to 10, ranged from 1.52 at the middle of the SOBP to 1.75 at the distal position and are in agreement with those previously reported from other carbon ion facilities. In conclusion, this first set of in vivo experiments shows that the CNAO carbon beam is radiobiologically comparable with the NIRS (National Institute of Radiological Sciences, Chiba, Japan) and GSI (Helmholtzzentrum für Schwerionenforschung, Darmstadt, Germany) ones. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Designing and assessing a sustainable networked delivery (SND) system: hybrid business-to-consumer book delivery case study.

    PubMed

    Kim, Junbeum; Xu, Ming; Kahhat, Ramzy; Allenby, Braden; Williams, Eric

    2009-01-01

    We attempted to design and assess an example of a sustainable networked delivery (SND) system: a hybrid business-to-consumer book delivery system. This system is intended to reduce costs, achieve significant reductions in energy consumption, and reduce environmental emissions of critical local pollutants and greenhouse gases. The energy consumption and concomitant emissions of this delivery system compared with existing alternative delivery systems were estimated. We found that regarding energy consumption, an emerging hybrid delivery system which is a sustainable networked delivery system (SND) would consume 47 and 7 times less than the traditional networked delivery system (TND) and e-commerce networked delivery system (END). Regarding concomitant emissions, in the case of CO2, the SND system produced 32 and 7 times fewer emissions than the TND and END systems. Also the SND system offer meaningful economic benefit such as the costs of delivery and packaging, to the online retailer, grocery, and consumer. Our research results show that the SND system has a lot of possibilities to save local transportation energy consumption and delivery costs, and reduce environmental emissions in delivery system.

  3. 38 CFR 4.46 - Accurate measurement.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.46 Accurate measurement. Accurate... indispensable in examinations conducted within the Department of Veterans Affairs. Muscle atrophy must also be...

  4. 38 CFR 4.46 - Accurate measurement.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.46 Accurate measurement. Accurate... indispensable in examinations conducted within the Department of Veterans Affairs. Muscle atrophy must also be...

  5. 38 CFR 4.46 - Accurate measurement.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.46 Accurate measurement. Accurate... indispensable in examinations conducted within the Department of Veterans Affairs. Muscle atrophy must also be...

  6. 38 CFR 4.46 - Accurate measurement.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.46 Accurate measurement. Accurate... indispensable in examinations conducted within the Department of Veterans Affairs. Muscle atrophy must also be...

  7. 38 CFR 4.46 - Accurate measurement.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.46 Accurate measurement. Accurate... indispensable in examinations conducted within the Department of Veterans Affairs. Muscle atrophy must also be...

  8. Feedback about More Accurate versus Less Accurate Trials: Differential Effects on Self-Confidence and Activation

    ERIC Educational Resources Information Center

    Badami, Rokhsareh; VaezMousavi, Mohammad; Wulf, Gabriele; Namazizadeh, Mahdi

    2012-01-01

    One purpose of the present study was to examine whether self-confidence or anxiety would be differentially affected by feedback from more accurate rather than less accurate trials. The second purpose was to determine whether arousal variations (activation) would predict performance. On Day 1, participants performed a golf putting task under one of…

  9. Mode of delivery following successful external cephalic version: comparison with spontaneous cephalic presentations at delivery.

    PubMed

    Kuppens, Simone M I; Hutton, Eileen K; Hasaart, Tom H M; Aichi, Nassira; Wijnen, Henrica A; Pop, Victor J M

    2013-10-01

    To compare the obstetric outcomes of pregnant women after successful external cephalic version (ECV) (cases) with a large group of pregnant women with a spontaneously occurring cephalic fetal position at delivery (controls). We conducted a retrospective matched cohort study in a teaching hospital in the Netherlands. Delivery outcomes of women with a successful ECV were compared with those of women with spontaneously occurring cephalic presentations, controlling for maternal age, parity, gestational age at delivery, and onset of labour (spontaneous or induced). Exclusion criteria were a history of Caesarean section, delivery at < 35 weeks, and elective Caesarean section. The primary outcome was the prevalence of Caesarean section and instrumental delivery in both groups; secondary outcomes were the characteristics of cases requiring intervention such as Caesarean section or instrumental delivery. Women who had a successful ECV had a significantly higher Caesarean section rate than the women in the control group (33/220 [15%] vs. 62/1030 [6.0 %]; P < 0.001). There was no difference in the incidence of instrumental delivery (20/220 [9.1%] vs. 103/1030 [10%]). Comparison of characteristics of women in the cases group showed that nulliparity, induction of labour, and occiput posterior presentation were associated with Caesarean section and instrumental deliveries. Compared with delivery of spontaneous cephalic presenta-tions, delivery of cephalic presenting babies following successful ECV is associated with an increased rate of Caesarean section, especially in nulliparous women and women whose labour is induced.

  10. Prenatal attitudes toward vaginal delivery and actual delivery mode: Variation by race/ethnicity and socioeconomic status.

    PubMed

    Attanasio, Laura B; Hardeman, Rachel R; Kozhimannil, Katy B; Kjerulff, Kristen H

    2017-12-01

    Researchers documenting persistent racial/ethnic and socioeconomic status disparities in chances of cesarean delivery have speculated that women's birth attitudes and preferences may partially explain these differences, but no studies have directly tested this hypothesis. We examined whether women's prenatal attitudes toward vaginal delivery differed by race/ethnicity or socioeconomic status, and whether attitudes were differently related to delivery mode depending on race/ethnicity or socioeconomic status. Data were from the First Baby Study, a cohort of 3006 women who gave birth to a first baby in Pennsylvania between 2009 and 2011. We used regression models to examine (1) predictors of prenatal attitudes toward vaginal delivery, and (2) the association between prenatal attitudes and actual delivery mode. To assess moderation, we estimated models adding interaction terms. Prenatal attitudes toward vaginal delivery were not associated with race/ethnicity or socioeconomic status. Positive attitudes toward vaginal delivery were associated with lower odds of cesarean delivery (AOR=0.60, P < .001). However, vaginal delivery attitudes were only related to delivery mode among women who were white, highly educated, and privately insured. There are racial/ethnic differences in chances of cesarean delivery, and these differences are not explained by birth attitudes. Furthermore, our findings suggest that white and high-socioeconomic status women may be more able to realize their preferences in childbirth. © 2017 Wiley Periodicals, Inc.

  11. Nanostructured materials for ocular delivery: nanodesign for enhanced bioadhesion, transepithelial permeability and sustained delivery

    PubMed Central

    Kim, Jean; Schlesinger, Erica B; Desai, Tejal A

    2015-01-01

    Effective drug delivery to the eye is an ongoing challenge due to poor patient compliance coupled with numerous physiological barriers. Eye drops for the front of the eye and ocular injections for the back of the eye are the most prevalent delivery methods, both of which require relatively frequent administration and are burdensome to the patient. Novel drug delivery techniques stand to drastically improve safety, efficacy and patient compliance for ocular therapeutics. Remarkable advances in nanofabrication technologies make the application of nanostructured materials to ocular drug delivery possible. This article focuses on the use of nanostructured materials with nanoporosity or nanotopography for ocular delivery. Specifically, we discuss nanotopography for enhanced bioadhesion and permeation and nanoporous materials for controlled release drug delivery. As examples, application of polymeric nanostructures for greater transepithelial permeability, nanostructured microparticles for enhanced preocular retention time and nanoporous membranes for tuning drug release profile are covered. PMID:26652282

  12. Image-Guided Drug Delivery with Single-Photon Emission Computed Tomography: A Review of Literature

    PubMed Central

    Chakravarty, Rubel; Hong, Hao; Cai, Weibo

    2014-01-01

    Tremendous resources are being invested all over the world for prevention, diagnosis, and treatment of various types of cancer. Successful cancer management depends on accurate diagnosis of the disease along with precise therapeutic protocol. The conventional systemic drug delivery approaches generally cannot completely remove the competent cancer cells without surpassing the toxicity limits to normal tissues. Therefore, development of efficient drug delivery systems holds prime importance in medicine and healthcare. Also, molecular imaging can play an increasingly important and revolutionizing role in disease management. Synergistic use of molecular imaging and targeted drug delivery approaches provides unique opportunities in a relatively new area called `image-guided drug delivery' (IGDD). Single-photon emission computed tomography (SPECT) is the most widely used nuclear imaging modality in clinical context and is increasingly being used to guide targeted therapeutics. The innovations in material science have fueled the development of efficient drug carriers based on, polymers, liposomes, micelles, dendrimers, microparticles, nanoparticles, etc. Efficient utilization of these drug carriers along with SPECT imaging technology have the potential to transform patient care by personalizing therapy to the individual patient, lessening the invasiveness of conventional treatment procedures and rapidly monitoring the therapeutic efficacy. SPECT-IGDD is not only effective for treatment of cancer but might also find utility in management of several other diseases. Herein, we provide a concise overview of the latest advances in SPECT-IGDD procedures and discuss the challenges and opportunities for advancement of the field. PMID:25182469

  13. Delivery of Chemotherapeutics Across the Blood–Brain Barrier: Challenges and Advances

    PubMed Central

    Doolittle, Nancy D.; Muldoon, Leslie L.; Culp, Aliana Y.; Neuwelt, Edward A.

    2017-01-01

    The blood–brain barrier (BBB) limits drug delivery to brain tumors. We utilize intraarterial infusion of hyperosmotic mannitol to reversibly open the BBB by shrinking endothelial cells and opening tight junctions between the cells. This approach transiently increases the delivery of chemotherapy, antibodies, and nanoparticles to brain. Our preclinical studies have optimized the BBB disruption (BBBD) technique and clinical studies have shown its safety and efficacy. The delivery of methotrexate-based chemotherapy in conjunction with BBBD provides excellent outcomes in primary central nervous system lymphoma (PCNSL) including stable or improved cognitive function in survivors a median of 12 years (range 2–26 years) after diagnosis. The addition of rituximab to chemotherapy with BBBD for PCNSL can be safely accomplished with excellent overall survival. Our translational studies of thiol agents to protect against platinum-induced toxicities led to the development of a two-compartment model in brain tumor patients. We showed that delayed high-dose sodium thiosulfate protects against carboplatin-induced hearing loss, providing the framework for large cooperative group trials of hearing chemoprotection. Neuroimaging studies have identified that ferumoxytol, an iron oxide nanoparticle blood pool agent, appears to be a superior contrast agent to accurately assess therapy-induced changes in brain tumor vasculature, in brain tumor response to therapy, and in differentiating central nervous system lesions with inflammatory components. This chapter reviews the breakthroughs, challenges, and future directions for BBBD. PMID:25307218

  14. Delivery of chemotherapeutics across the blood-brain barrier: challenges and advances.

    PubMed

    Doolittle, Nancy D; Muldoon, Leslie L; Culp, Aliana Y; Neuwelt, Edward A

    2014-01-01

    The blood-brain barrier (BBB) limits drug delivery to brain tumors. We utilize intraarterial infusion of hyperosmotic mannitol to reversibly open the BBB by shrinking endothelial cells and opening tight junctions between the cells. This approach transiently increases the delivery of chemotherapy, antibodies, and nanoparticles to brain. Our preclinical studies have optimized the BBB disruption (BBBD) technique and clinical studies have shown its safety and efficacy. The delivery of methotrexate-based chemotherapy in conjunction with BBBD provides excellent outcomes in primary central nervous system lymphoma (PCNSL) including stable or improved cognitive function in survivors a median of 12 years (range 2-26 years) after diagnosis. The addition of rituximab to chemotherapy with BBBD for PCNSL can be safely accomplished with excellent overall survival. Our translational studies of thiol agents to protect against platinum-induced toxicities led to the development of a two-compartment model in brain tumor patients. We showed that delayed high-dose sodium thiosulfate protects against carboplatin-induced hearing loss, providing the framework for large cooperative group trials of hearing chemoprotection. Neuroimaging studies have identified that ferumoxytol, an iron oxide nanoparticle blood pool agent, appears to be a superior contrast agent to accurately assess therapy-induced changes in brain tumor vasculature, in brain tumor response to therapy, and in differentiating central nervous system lesions with inflammatory components. This chapter reviews the breakthroughs, challenges, and future directions for BBBD. © 2014 Elsevier Inc. All rights reserved.

  15. Failed Operative Vaginal Delivery

    PubMed Central

    Alexander, James M.; Leveno, Kenneth J.; Hauth, John C.; Landon, Mark B.; Gilbert, Sharon; Spong, Catherine Y.; Varner, Michael W.; Caritis, Steve N.; Meis, Paul; Wapner, Ronald J.; Sorokin, Yoram; Miodovnik, Menachem; O'Sullivan, Mary J.; Sibai, Baha M.; Langer, Oded; Gabbe, Steven G.

    2010-01-01

    Objective To compare maternal and neonatal outcomes in women undergoing a second stage cesarean after a trial of operative vaginal delivery with women undergoing a second stage cesarean without such an attempt. Methods This study is a secondary analysis of the women who underwent second stage cesarean. .The maternal outcomes examined included blood transfusion, endometritis, wound complication, anesthesia use, and maternal death. Infant outcomes examined included umbilical artery pH < 7.0, Apgar of 3 or less at 5 minutes, seizures within 24 hours of birth, hypoxic ischemic encephalopathy (HIE), stillbirth, skull fracture, and neonatal death. Results Of 3189 women who underwent second stage cesarean, operative vaginal delivery was attempted in 640. Labor characteristics were similar in the two groups with the exception of the admission to delivery time and cesarean indication. Those with an attempted operative vaginal delivery were more likely to undergo cesarean delivery for a non-reassuring fetal heart rate tracing (18.0% vs 13.9%, p=.01), have a wound complication (2.7% vs 1.0%; OR 2.65 95% CI 1.43–4.91), and require general anesthesia (8.0% vs 4.1%, OR 2.05 95% CI 1.44–2.91). Neonatal outcomes including umbilical artery pH less than 7.0, Apgar at or below 3 at 5 minutes, and hypoxic ischemic encephalopathy were more common for those with an attempted operative vaginal delivery. This was not significant when cases with a non-reassuring fetal heart rate tracing were removed. Conclusion Cesarean delivery after an attempt at operative vaginal delivery was not associated with adverse neonatal outcomes in the absence of a non-reassuring fetal heart rate tracing. PMID:20168101

  16. Nanostructure-mediated drug delivery.

    PubMed

    Hughes, Gareth A

    2005-03-01

    Nanotechnology is expected to have an impact on all industries including semiconductors, manufacturing, and biotechnology. Tools that provide the capability to characterize and manipulate materials at the nanoscale level further elucidate nanoscale phenomena and equip researchers and developers with the ability to fabricate novel materials and structures. One of the most promising societal impacts of nanotechnology is in the area of nanomedicine. Personalized health care, rational drug design, and targeted drug delivery are some of the benefits of a nanomedicine-based approach to therapy. This review will focus on the development of nanoscale drug delivery mechanisms. Nanostructured drug carriers allow for the delivery of not only small-molecule drugs but also the delivery of nucleic acids and proteins. Delivery of these molecules to specific areas within the body can be achieved, which will reduce systemic side effects and allow for more efficient use of the drug.

  17. When microchip implants do more than drug delivery: blending, blurring, and bundling of protected health information and patient monitoring.

    PubMed

    Bramstedt, Katrina A

    2005-01-01

    Although currently in the research stage, scientists argue that drug-releasing microchip implants are on the horizon for future patients. This paper presents ethical reflection on these implants and identifies specific areas of concern; namely, patient monitoring and tracking, and patient privacy and confidentiality. It is foreseeable that drug delivery chips could be multifunctional with the overt or covert addition of sensors that monitor more than just the bloodstream concentrations of prescribed drugs (e.g., cotinine and alcohol in non-compliant patients, patient location via radio frequency or global positioning satellite). Similarly, it is foreseeable that these chips could be embedded with a patient's protected health information that could potentially be accessed and used by unauthorized persons. While drug delivery microchips are theoretically convenient and accurate for dosing, and might offer faster drug delivery with fewer side effects, ethical issues loom and should be contemplated now, while the technology is still under development.

  18. Accurate O2 delivery enabled benzene biodegradation through aerobic activation followed by denitrification-coupled mineralization.

    PubMed

    Liu, Zhuolin; Zhou, Chen; Ontiveros-Valencia, Aura; Luo, Yi-Hao; Long, Min; Xu, Hua; Rittmann, Bruce E

    2018-04-28

    Although benzene can be biodegraded when dissolved oxygen is sufficient, delivering oxygen is energy intensive and can lead to air stripping the benzene. Anaerobes can biodegrade benzene by using electron acceptors other than O 2 , and this may reduce costs and exposure risks; the drawback is a remarkably slower growth rate. We evaluated a two-step strategy that involved O 2 -dependent benzene activation and cleavage followed by intermediate oxidation coupled to NO 3 - respiration. We employed a membrane biofilm reactor (MBfR) featuring nonporous hollow fibers as the means to deliver O 2 directly to a biofilm at an accurately controlled rate. Benzene was mineralized aerobically when the O 2 -supply rate was more than sufficient for mineralization. As the O 2 -supply capacity was systematically lowered, O 2 respiration was gradually replaced by NO 3 - respiration. When the maximum O 2 -supply capacity was only 20% of the demand for benzene mineralization, O 2 was used almost exclusively for benzene activation and cleavage, while respiration was almost only by denitrification. Analyses of microbial community structure and predicted metagenomic function reveal that Burkholderiales was dominant and probably utilized monooxygenase activation, with subsequent mineralization coupled to denitrification; strict anaerobes capable of carboxylative activation were not detected. These results open the door for a promising treatment strategy that simultaneously ameliorates technical and economic challenges of aeration and slow kinetics of anaerobic activation of aromatics. © 2018 Wiley Periodicals, Inc.

  19. Microprocessor controlled transdermal drug delivery.

    PubMed

    Subramony, J Anand; Sharma, Ashutosh; Phipps, J B

    2006-07-06

    Transdermal drug delivery via iontophoresis is reviewed with special focus on the delivery of lidocaine for local anesthesia and fentanyl for patient controlled acute therapy such as postoperative pain. The role of the microprocessor controller in achieving dosimetry, alternating/reverse polarity, pre-programmed, and sensor-based delivery is highlighted. Unique features such as the use of tactile signaling, telemetry control, and pulsatile waveforms in iontophoretic drug delivery are described briefly.

  20. Does the novel delivery system for the STENTYS self-apposing coronary stent increase the risk of stent edge dissections? Optical coherence tomography post stent findings.

    PubMed

    Lu, Huangling; Kalkman, Deborah N; Grundeken, Maik J; Tijssen, Jan G P; Wykrzykowska, Joanna J; de Winter, Robbert J; Koch, Karel T

    2018-02-01

    With optical coherence tomography (OCT), details of arterial injuries during percutaneous coronary intervention can be assessed accurately. There might be an increased risk of stent edge dissections with the novel delivery system for the STENTYS stent. We evaluated the prevalence of stent edge dissections using the novel Xposition delivery device as compared with the conventional delivery device. A total of 38 patients who were treated with the self-apposing STENTYS stent and with OCT assessment at our center were retrospectively analysed. Twenty patients were treated using the Xposition- and 18 using the conventional delivery device. OCT was performed according to study protocol. Frames with poor quality were excluded. A total of 12(18%) dissections were detected, 7(20%) in the Xposition delivery device group, and 5(15%) in the conventional group (p = 1). Using the Xposition delivery device 4(33%) dissections were found proximally, using the conventional delivery device 3(25%) (p = ns). Mean longitudinal dissection length was 2.07 ± 1.80mm, 8(67%) appeared as flaps, 4(33%) as cavities. Morphometric parameters were comparable in both groups. Detailed OCT assessment of stent edge dissections was possible, which revealed no large differences using the Xposition delivery device as compared with conventional delivery device, however large studies are warranted.

  1. Design of Drug Delivery Methods for the Brain and Central Nervous System

    NASA Astrophysics Data System (ADS)

    Lueshen, Eric

    Due to the impermeability of the blood-brain barrier (BBB) to macromolecules delivered systemically, drug delivery to the brain and central nervous system (CNS) is quite difficult and has become an area of intense research. Techniques such as convection-enhanced intraparenchymal delivery and intrathecal magnetic drug targeting offer a means of circumventing the blood-brain barrier for targeted delivery of therapeutics. This dissertation focuses on three aspects of drug delivery: pharmacokinetics, convection-enhanced delivery, and intrathecal magnetic drug targeting. Classical pharmacokinetics mainly uses black-box curve fitting techniques without biochemical or biological basis. This dissertation advances the state-of-the-art of pharmacokinetics and pharmacodynamics by incorporating first principles and biochemical/biotransport mechanisms in the prediction of drug fate in vivo. A whole body physiologically-based pharmacokinetics (PBPK) modeling framework is engineered which creates multiscale mathematical models for entire organisms composed of organs, tissues, and a detailed vasculature network to predict drug bioaccumulation and to rigorously determine kinetic parameters. These models can be specialized to account for species, weight, gender, age, and pathology. Systematic individual therapy design using the proposed mechanistic PBPK modeling framework is also a possibility. Biochemical, anatomical, and physiological scaling laws are also developed to accurately project drug kinetics in humans from small animal experiments. Our promising results demonstrate that the whole-body mechanistic PBPK modeling approach not only elucidates drug mechanisms from a biochemical standpoint, but offers better scaling precision. Better models can substantially accelerate the introduction of drug leads to clinical trials and eventually to the market by offering more understanding of the drug mechanisms, aiding in therapy design, and serving as an accurate dosing tool. Convection

  2. Accurate respiration measurement using DC-coupled continuous-wave radar sensor for motion-adaptive cancer radiotherapy.

    PubMed

    Gu, Changzhan; Li, Ruijiang; Zhang, Hualiang; Fung, Albert Y C; Torres, Carlos; Jiang, Steve B; Li, Changzhi

    2012-11-01

    Accurate respiration measurement is crucial in motion-adaptive cancer radiotherapy. Conventional methods for respiration measurement are undesirable because they are either invasive to the patient or do not have sufficient accuracy. In addition, measurement of external respiration signal based on conventional approaches requires close patient contact to the physical device which often causes patient discomfort and undesirable motion during radiation dose delivery. In this paper, a dc-coupled continuous-wave radar sensor was presented to provide a noncontact and noninvasive approach for respiration measurement. The radar sensor was designed with dc-coupled adaptive tuning architectures that include RF coarse-tuning and baseband fine-tuning, which allows the radar sensor to precisely measure movement with stationary moment and always work with the maximum dynamic range. The accuracy of respiration measurement with the proposed radar sensor was experimentally evaluated using a physical phantom, human subject, and moving plate in a radiotherapy environment. It was shown that respiration measurement with radar sensor while the radiation beam is on is feasible and the measurement has a submillimeter accuracy when compared with a commercial respiration monitoring system which requires patient contact. The proposed radar sensor provides accurate, noninvasive, and noncontact respiration measurement and therefore has a great potential in motion-adaptive radiotherapy.

  3. Elective Delivery Before 39 Weeks

    MedlinePlus

    ... Delivery, and Postpartum Care Elective Delivery Before 39 Weeks • What is a “medically indicated” delivery? • What is ... the baby grow and develop during the last weeks of pregnancy? • What are the risks for babies ...

  4. Nanomedicine in pulmonary delivery

    PubMed Central

    Mansour, Heidi M; Rhee, Yun-Seok; Wu, Xiao

    2009-01-01

    The lung is an attractive target for drug delivery due to noninvasive administration via inhalation aerosols, avoidance of first-pass metabolism, direct delivery to the site of action for the treatment of respiratory diseases, and the availability of a huge surface area for local drug action and systemic absorption of drug. Colloidal carriers (ie, nanocarrier systems) in pulmonary drug delivery offer many advantages such as the potential to achieve relatively uniform distribution of drug dose among the alveoli, achievement of improved solubility of the drug from its own aqueous solubility, a sustained drug release which consequently reduces dosing frequency, improves patient compliance, decreases incidence of side effects, and the potential of drug internalization by cells. This review focuses on the current status and explores the potential of colloidal carriers (ie, nanocarrier systems) in pulmonary drug delivery with special attention to their pharmaceutical aspects. Manufacturing processes, in vitro/in vivo evaluation methods, and regulatory/toxicity issues of nanomedicines in pulmonary delivery are also discussed. PMID:20054434

  5. Noninvasive ocular drug delivery: potential transcorneal and other alternative delivery routes for therapeutic molecules in glaucoma.

    PubMed

    Foldvari, Marianna

    2014-01-01

    Drug delivery to the eye is made difficult by multiple barriers (such as the tear film, cornea, and vitreous) between the surface of the eye and the treatment site. These barriers are difficult to surmount for the purposes of drug delivery without causing toxicity. Using nanotechnology tools to control, manipulate, and study delivery systems, new approaches to delivering drugs, genes, and antigens that are effective and safe can be developed. Topical administration to the ocular surface would be the safest method for delivery, as it is noninvasive and painless compared with other delivery methods. However, there is only limited success using topical delivery methods, especially for gene therapy. Current thinking on treatments of the future enabled by nanodelivery systems and the identification of target specificity parameters that require deeper understanding to develop successful topical delivery systems for glaucoma is highlighted.

  6. [Fathers of first infants--preparatory courses about delivery, experience of delivery and paternity leave].

    PubMed

    Aagaard, J; Dueholm, M; Nielsen, K T; Wiese, J; Strand, J E; Jangaard, J K

    1989-05-22

    In the Central Hospital in Randers, 233 fathers of first infants replied to a questionnaire which illustrated their attitudes to the preparatory courses about delivery, experience of delivery and attitudes to paternity leave. 65% of the fathers participated in the course and 74% stated that they considered that this had been profitable. Where 77% of the men were concerned, these considered that participation in delivery had been a positive experience. 73% of the men had planned paternity leave around the time of delivery, which emphasizes the need for this arrangement.

  7. Transforaminal lumbar interbody graft placement using an articulating delivery arm facilitates increased segmental lordosis with superior anterior and midline graft placement.

    PubMed

    Shau, David N; Parker, Scott L; Mendenhall, Stephen K; Zuckerman, Scott L; Godil, Saniya S; Devin, Clinton J; McGirt, Matthew J

    2015-05-01

    Transforaminal lumbar interbody fusion (TLIF) is a frequently performed method of lumbar arthrodesis in patients failing medical management of back and leg pain. Accurate placement of the interbody graft and restoration of lordosis has been shown to be crucial when performing lumbar fusion procedures. We performed a single-surgeon, prospective, randomized study to determine whether a novel articulating versus traditional straight graft delivery arm system allows for superior graft placement and increased lordosis for single-level TLIF. Thirty consecutive patients undergoing single-level TLIF were included and prospectively randomized to one of the 2 groups (articulated vs. straight delivery arm system). Three radiographic characteristics were evaluated at 6-week follow-up: (1) degree of segmental lumbar lordosis at the fused level; (2) the percent anterior location of the interbody graft in disk space; and (3) the distance (mm) off midline of the interbody graft placement. Randomization yielded 16 patients in the articulated delivery arm cohort and 14 in the straight delivery arm cohort. The articulating delivery arm system yielded an average of 14.7-degree segmental lordosis at fused level, 35% anterior location, and 3.6 mm off midline. The straight delivery arm system yielded an average of 10.7-degree segmental lordosis at fused level, 46% anterior location, and 7.0 mm off midline. All 3 comparisons were statistically significant (P<0.05). The study suggests that an articulating delivery arm system facilitates superior anterior and midline TLIF graft placement allowing for increased segmental lordosis compared with a traditional straight delivery arm system.

  8. Managing the delivery of bad news: an in-depth analysis of doctors' delivery style.

    PubMed

    Shaw, Joanne; Dunn, Stewart; Heinrich, Paul

    2012-05-01

    The purpose of this study was to identify and describe the delivery styles doctors typically use when breaking bad news (BBN). Thirty one doctors were recruited to participate in two standardised BBN consultations involving a sudden death. Delivery styles were determined using time to deliver the bad news as a standardised differentiation as well as qualitative analysis of interaction content and language style. Communication performance was also assessed. Analysis of BBN interactions revealed three typical delivery styles. A blunt style characterised by doctors delivering news within the first 30 s of the interaction; Forecasting, a staged delivery of the news within the first 2 min and a stalling approach, delaying news delivery for more than 2 min. This latter avoidant style relies on the news recipient reaching a conclusion about event outcome without the doctor explicitly conveying the news. Three typical bad news delivery styles used by doctors when BBN were confirmed both semantically and operationally in the study. The relationship between delivery style and the overall quality of BBN interactions was also investigated. This research provides a new template for approaching BBN training and provides evidence for a need for greater flexibility when communicating bad news. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  9. The optimal mode of delivery for the haemophilia carrier expecting an affected infant is vaginal delivery.

    PubMed

    Ljung, R

    2010-05-01

    The optimal mode of delivery of a haemophilia carrier expecting a child is still a matter of uncertainty and debate. The aim of this commentary/review is to suggest that normal vaginal delivery should be the recommended mode of delivery for the majority of carriers, based on review of studies on obstetric aspects of haemophilia. About 2.0-4.0% of all haemophilia boys born in countries with a good standard of health care will suffer from ICH during the neonatal period. This is an average figure including all modes of delivery and regardless of whether the carrier status of the mother or the haemophilia status of the foetus was known or not at the time of delivery. On the basis of current literature, one may conclude that the risk of serious bleeding in the neonate affected with haemophilia is small in conjunction with normal vaginal delivery. It should be possible to further reduce the low frequency of complications if appropriate precautions are taken when planning the delivery in pregnant woman with known carrier status, if the sex of the foetus is known and, even more, when the haemophilia status of the foetus is known. Instrumental delivery such as use of vacuum extraction and foetal scalp monitors must be avoided at delivery of carriers.

  10. Multi-channel gas-delivery system

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

    Rozenzon, Yan; Trujillo, Robert T.; Beese, Steven C.

    One embodiment of the present invention provides a gas-delivery system for delivering reaction gas to a reactor chamber. The gas-delivery system includes a main gas-inlet port for receiving reaction gases and a gas-delivery plate that includes a plurality of gas channels. A gas channel includes a plurality of gas holes for allowing the reaction gases to enter the reactor chamber from the gas channel. The gas-delivery system further includes a plurality of sub-gas lines coupling together the main gas-inlet port and the gas-delivery plate, and a respective sub-gas line is configured to deliver a portion of the received reaction gasesmore » to a corresponding gas channel.« less

  11. An Audit of Singleton Breech Deliveries in a Hospital with a High Rate of Vaginal Delivery

    PubMed Central

    Nordin, Noraihan Mohd.

    2007-01-01

    The term breech trial (TBT) has brought about radical changes but it is debatable whether it provides unequivocal evidence regarding the practice of breech deliveries. There is a need to publish the data of a study that was performed before the era of the TBT in a hospital where there was a high rate of breech vaginal delivery. The objectives were to ascertain the incidence, mode of delivery and fetal outcome in singleton breech deliveries. The study design was a retrospective cohort study where 165 consecutive breech and 165 controls (cephalic) were included. Statistical analysis, used were Chi squared and Fischer’s exact test. P<0.05 is taken as the level of significance. The incidence of breech deliveries was found to be 3% and has remained fairly constant but the rate of breech vaginal delivery has fallen and the CS rates have increased. Even though more breech compared to controls were significantly sectioned, majority of the breeches {n=137 (83%)} were planned for vaginal delivery and in these patients two-thirds attained vaginal delivery. There was 1 fetal death in the CS group compared to 12 deaths in the vaginally delivered breech. However, most death in the breech delivered vaginally are unavoidable. In conclusion, there is a high rate of breech vaginal delivery in this series of patients and most perinatal deaths were not related to the mode of delivery. PMID:22593649

  12. 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…

  13. Polymers for Drug Delivery Systems

    PubMed Central

    Liechty, William B.; Kryscio, David R.; Slaughter, Brandon V.; Peppas, Nicholas A.

    2012-01-01

    Polymers have played an integral role in the advancement of drug delivery technology by providing controlled release of therapeutic agents in constant doses over long periods, cyclic dosage, and tunable release of both hydrophilic and hydrophobic drugs. From early beginnings using off-the-shelf materials, the field has grown tremendously, driven in part by the innovations of chemical engineers. Modern advances in drug delivery are now predicated upon the rational design of polymers tailored for specific cargo and engineered to exert distinct biological functions. In this review, we highlight the fundamental drug delivery systems and their mathematical foundations and discuss the physiological barriers to drug delivery. We review the origins and applications of stimuli-responsive polymer systems and polymer therapeutics such as polymer-protein and polymer-drug conjugates. The latest developments in polymers capable of molecular recognition or directing intracellular delivery are surveyed to illustrate areas of research advancing the frontiers of drug delivery. PMID:22432577

  14. 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

  15. EPR/alanine dosimetry for two therapeutic proton beams

    NASA Astrophysics Data System (ADS)

    Marrale, Maurizio; Carlino, Antonio; Gallo, Salvatore; Longo, Anna; Panzeca, Salvatore; Bolsi, Alessandra; Hrbacek, Jan; Lomax, Tony

    2016-02-01

    In this work the analysis of the electron paramagnetic resonance (EPR) response of alanine pellets exposed to two different clinical proton beams employed for radiotherapy is performed. One beam is characterized by a passive delivery technique and is dedicated to the eyes treatment (OPTIS2 beam line). Alanine pellets were irradiated with a 70 MeV proton beam corresponding to 35 mm range in eye tissue. We investigated how collimators with different sizes and shape used to conform the dose to the planned target volume influence the delivered dose. For this purpose we performed measurements with varying the collimator size (Output Factor) and the results were compared with those obtained with other dosimetric techniques (such as Markus chamber and diode detector). This analysis showed that the dosimeter response is independent of collimator diameter if this is larger than or equal to 10 mm. The other beam is characterized by an active spot-scanning technique, the Gantry1 beam line (maximum energy 230 MeV), and is used to treat deep-seated tumors. The dose linearity of alanine response in the clinical dose range was tested and the alanine dose response at selected locations in depth was measured and compared with the TPS planned dose in a quasi-clinical scenario. The alanine response was found to be linear in the dose in the clinical explored range (from 10 to 70 Gy). Furthermore, a depth dose profile in a quasi-clinical scenario was measured and compared to the dose computed by the Treatment Planning System PSIPLAN. The comparison of calibrated proton alanine measurements and TPS dose shows a difference under 1% in the SOBP and a "quenching" effect up to 4% in the distal part of SOBP. The positive dosimetric characteristics of the alanine pellets confirm the feasibility to use these detectors for "in vivo" dosimetry in clinical proton beams.

  16. MO-G-BRE-04: Automatic Verification of Daily Treatment Deliveries and Generation of Daily Treatment Reports for a MR Image-Guided Treatment Machine

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

    Yang, D; Li, X; Li, H

    2014-06-15

    Purpose: Two aims of this work were to develop a method to automatically verify treatment delivery accuracy immediately after patient treatment and to develop a comprehensive daily treatment report to provide all required information for daily MR-IGRT review. Methods: After systematically analyzing the requirements for treatment delivery verification and understanding the available information from a novel MR-IGRT treatment machine, we designed a method to use 1) treatment plan files, 2) delivery log files, and 3) dosimetric calibration information to verify the accuracy and completeness of daily treatment deliveries. The method verifies the correctness of delivered treatment plans and beams, beammore » segments, and for each segment, the beam-on time and MLC leaf positions. Composite primary fluence maps are calculated from the MLC leaf positions and the beam-on time. Error statistics are calculated on the fluence difference maps between the plan and the delivery. We also designed the daily treatment delivery report by including all required information for MR-IGRT and physics weekly review - the plan and treatment fraction information, dose verification information, daily patient setup screen captures, and the treatment delivery verification results. Results: The parameters in the log files (e.g. MLC positions) were independently verified and deemed accurate and trustable. A computer program was developed to implement the automatic delivery verification and daily report generation. The program was tested and clinically commissioned with sufficient IMRT and 3D treatment delivery data. The final version has been integrated into a commercial MR-IGRT treatment delivery system. Conclusion: A method was developed to automatically verify MR-IGRT treatment deliveries and generate daily treatment reports. Already in clinical use since December 2013, the system is able to facilitate delivery error detection, and expedite physician daily IGRT review and physicist weekly

  17. A high-speed scintillation-based electronic portal imaging device to quantitatively characterize IMRT delivery.

    PubMed

    Ranade, Manisha K; Lynch, Bart D; Li, Jonathan G; Dempsey, James F

    2006-01-01

    We have developed an electronic portal imaging device (EPID) employing a fast scintillator and a high-speed camera. The device is designed to accurately and independently characterize the fluence delivered by a linear accelerator during intensity modulated radiation therapy (IMRT) with either step-and-shoot or dynamic multileaf collimator (MLC) delivery. Our aim is to accurately obtain the beam shape and fluence of all segments delivered during IMRT, in order to study the nature of discrepancies between the plan and the delivered doses. A commercial high-speed camera was combined with a terbium-doped gadolinium-oxy-sulfide (Gd2O2S:Tb) scintillator to form an EPID for the unaliased capture of two-dimensional fluence distributions of each beam in an IMRT delivery. The high speed EPID was synchronized to the accelerator pulse-forming network and gated to capture every possible pulse emitted from the accelerator, with an approximate frame rate of 360 frames-per-second (fps). A 62-segment beam from a head-and-neck IMRT treatment plan requiring 68 s to deliver was recorded with our high speed EPID producing approximately 6 Gbytes of imaging data. The EPID data were compared with the MLC instruction files and the MLC controller log files. The frames were binned to provide a frame rate of 72 fps with a signal-to-noise ratio that was sufficient to resolve leaf positions and segment fluence. The fractional fluence from the log files and EPID data agreed well. An ambiguity in the motion of the MLC during beam on was resolved. The log files reported leaf motions at the end of 33 of the 42 segments, while the EPID observed leaf motions in only 7 of the 42 segments. The static IMRT segment shapes observed by the high speed EPID were in good agreement with the shapes reported in the log files. The leaf motions observed during beam-on for step-and-shoot delivery were not temporally resolved by the log files.

  18. Characterization of particulate drug delivery systems for oral delivery of Peptide and protein drugs.

    PubMed

    Christophersen, Philip Carsten; Fano, Mathias; Saaby, Lasse; Yang, Mingshi; Nielsen, Hanne Mørck; Mu, Huiling

    2015-01-01

    Oral drug delivery is a preferred route because of good patient compliance. However, most peptide/ protein drugs are delivered via parenteral routes because of the absorption barriers in the gastrointestinal (GI) tract such as enzymatic degradation by proteases and low permeability acrossthe biological membranes. To overcome these barriers, different formulation strategies for oral delivery of biomacromolecules have been proposed, including lipid based formulations and polymer-based particulate drug delivery systems (DDS). The aim of this review is to summarize the existing knowledge about oral delivery of peptide/protein drugs and to provide an overview of formulationand characterization strategies. For a better understanding of the challenges in oral delivery of peptide/protein drugs, the composition of GI fluids and the digestion processes of different kinds of excipients in the GI tract are summarized. Additionally, the paper provides an overview of recent studies on characterization of solid drug carriers for peptide/protein drugs, drug distribution in particles, drug release and stability in simulated GI fluids, as well as the absorption of peptide/protein drugs in cell-based models. The use of biorelevant media when applicable can increase the knowledge about the quality of DDS for oral protein delivery. Hopefully, the knowledge provided in this review will aid the establishment of improved biorelevant models capable of forecasting the performance of particulate DDS for oral peptide/protein delivery.

  19. Pregnancy week at delivery and the risk of shoulder dystocia: a population study of 2,014,956 deliveries.

    PubMed

    Øverland, E A; Vatten, L J; Eskild, A

    2014-01-01

    To study whether pregnancy week at delivery is an independent risk factor for shoulder dystocia. Population study. Medical Birth Registry of Norway. All vaginal deliveries of singleton offspring in cephalic presentation in Norway during 1967 through 2009 (n = 2,014,956). The incidence of shoulder dystocia was calculated according to pregnancy week at delivery. The associations of pregnancy week at delivery with shoulder dystocia were estimated as crude and adjusted odds ratios using logistic regression analyses. We repeated the analyses in pregnancies with and without maternal diabetes. Shoulder dystocia at delivery. The overall incidence of shoulder dystocia was 0.73% (n = 14,820), and the incidence increased by increasing pregnancy week at delivery. Birthweight was strongly associated with shoulder dystocia. After adjustment for birthweight, induction of labour, use of epidural analgesia at delivery, prolonged labour, forceps-assisted and vacuum-assisted delivery, parity, period of delivery and maternal age in multivariable analyses, the adjusted odds ratios for shoulder dystocia were 1.77 (1.42-2.20) for deliveries at 32-35 weeks of gestation, and 0.84 (0.79-0.88) at 42-43 weeks of gestation, using weeks 40-41 as the reference. In pregnancies affected by diabetes (n = 11,188), the incidence of shoulder dystocia was 3.95%, and after adjustment for birthweight the adjusted odds ratio for shoulder dystocia was 2.92 (95% CI 1.54-5.52) for deliveries at weeks 32-35 of gestation, and 0.91 (95% CI 0.50-1.66) at 42-43 weeks of gestation. The risk of shoulder dystocia was associated with increased birthweight, diabetes, induction of labour, use of epidural analgesia at delivery, prolonged labour, forceps-assisted and vacuum-assisted delivery, parity and period of delivery but not with post-term delivery. © 2013 Royal College of Obstetricians and Gynaecologists.

  20. Cytosolic delivery: Just passing through

    NASA Astrophysics Data System (ADS)

    Sánchez-Navarro, Macarena; Teixidó, Meritxell; Giralt, Ernest

    2017-08-01

    Intracellular protein delivery has been a major challenge in the field of cell biology for decades. Engineering such delivery is a key step in the development of protein- and antibody-based therapeutics. Now, two different approaches that enable the delivery of antibodies and antibody fragments into the cytosol have been developed.

  1. Biomaterials for drug delivery systems.

    PubMed

    Buckles, R G

    1983-01-01

    Drug delivery systems have unusual materials requirements which derive mainly from their therapeutic role: to administer drugs over prolonged periods of time at rates that are independent of patient-to-patient variables. The chemical nature of the surfaces of such devices may stimulate biorejection processes which can be enhanced or suppressed by the simultaneous presence of the drug that is being administered. Selection of materials for such systems is further complicated by the need for compatibility with the drug contained within the system. A review of selected drug delivery systems is presented. This leads to a definition of the technologies required to develop successfully such systems as well as to categorize the classes of drug delivery systems available to the therapist. A summary of the applications of drug delivery systems will also be presented. There are five major challenges to the biomaterials scientist: (1) how to minimize the influence on delivery rate of the transient biological response that accompanies implantation of any object; (2) how to select a composition, size, shape, and flexibility that optimizes biocompatibility; (3) how to make an intravascular delivery system that will retain long-term functionality; (4) how to make a percutaneous lead for those delivery systems that cannot be implanted but which must retain functionality for extended periods; and (5) how to make biosensors of adequate compatibility and stability to use with the ultimate drug delivery system-a system that operates with feedback control.

  2. Intranasal delivery: physicochemical and therapeutic aspects.

    PubMed

    Costantino, Henry R; Illum, Lisbeth; Brandt, Gordon; Johnson, Paul H; Quay, Steven C

    2007-06-07

    Interest in intranasal (IN) administration as a non-invasive route for drug delivery continues to grow rapidly. The nasal mucosa offers numerous benefits as a target issue for drug delivery, such as a large surface area for delivery, rapid drug onset, potential for central nervous system delivery, and no first-pass metabolism. A wide variety of therapeutic compounds can be delivered IN, including relatively large molecules such as peptides and proteins, particularly in the presence of permeation enhancers. The current review provides an in-depth discussion of therapeutic aspects of IN delivery including consideration of the intended indication, regimen, and patient population, as well as physicochemical properties of the drug itself. Case examples are provided to illustrate the utility of IN dosing. It is anticipated that the present review will prove useful for formulation scientists considering IN delivery as a delivery route.

  3. Adenosine-Associated Delivery Systems

    PubMed Central

    Kazemzadeh-Narbat, Mehdi; Annabi, Nasim; Tamayol, Ali; Oklu, Rahmi; Ghanem, Amyl; Khademhosseini, Ali

    2016-01-01

    Adenosine is a naturally occurring purine nucleoside in every cell. Many critical treatments such as modulating irregular heartbeat (arrhythmias), regulation of central nervous system (CNS) activity, and inhibiting seizural episodes can be carried out using adenosine. Despite the significant potential therapeutic impact of adenosine and its derivatives, the severe side effects caused by their systemic administration have significantly limited their clinical use. In addition, due to adenosine’s extremely short half-life in human blood (less than 10 s), there is an unmet need for sustained delivery systems to enhance efficacy and reduce side effects. In this paper, various adenosine delivery techniques, including encapsulation into biodegradable polymers, cell-based delivery, implantable biomaterials, and mechanical-based delivery systems, are critically reviewed and the existing challenges are highlighted. PMID:26453156

  4. MEMS: Enabled Drug Delivery Systems.

    PubMed

    Cobo, Angelica; Sheybani, Roya; Meng, Ellis

    2015-05-01

    Drug delivery systems play a crucial role in the treatment and management of medical conditions. Microelectromechanical systems (MEMS) technologies have allowed the development of advanced miniaturized devices for medical and biological applications. This Review presents the use of MEMS technologies to produce drug delivery devices detailing the delivery mechanisms, device formats employed, and various biomedical applications. The integration of dosing control systems, examples of commercially available microtechnology-enabled drug delivery devices, remaining challenges, and future outlook are also discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. 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

  6. 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

  7. 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.

  8. Effect of obesity on preterm delivery prediction by transabdominal recording of uterine electromyography.

    PubMed

    Lucovnik, Miha; Chambliss, Linda R; Blumrick, Richard; Balducci, James; Gersak, Ksenija; Garfield, Robert E

    2016-10-01

    It has been shown that noninvasive uterine electromyography (EMG) can identify true preterm labor more accurately than methods available to clinicians today. The objective of this study was to evaluate the effect of body mass index (BMI) on the accuracy of uterine EMG in predicting preterm delivery. Predictive values of uterine EMG for preterm delivery were compared in obese versus overweight/normal BMI patients. Hanley-McNeil test was used to compare receiver operator characteristics curves in these groups. Previously reported EMG cutoffs were used to determine groups with false positive/false negative and true positive/true negative EMG results. BMI in these groups was compared with Student t test (p < 0.05 significant). A total of 88 patients were included: 20 obese, 64 overweight, and four with normal BMI. EMG predicted preterm delivery within 7 days with area under the curve = 0.95 in the normal/overweight group, and with area under the curve = 1.00 in the obese group (p = 0.08). Six patients in true preterm labor (delivering within 7 days from EMG measurement) had low EMG values (false negative group). There were no false positive results. No significant differences in patient's BMI were noted between false negative group patients and preterm labor patients with high EMG values (true positive group) and nonlabor patients with low EMG values (true negative group; p = 0.32). Accuracy of noninvasive uterine EMG monitoring and its predictive value for preterm delivery are not affected by obesity. Copyright © 2016. Published by Elsevier B.V.

  9. Hematological and TGF-beta variations after whole-body proton irradiation

    NASA Technical Reports Server (NTRS)

    Kajioka, E. H.; Andres, M. L.; Mao, X. W.; Moyers, M. F.; Nelson, G. A.; Gridley, D. S.

    2000-01-01

    The acute effects of proton whole-body irradiation on five bone-marrow-derived cell types and transforming growth factor-beta 1 (TGF-beta 1) were examined and compared to the effects of photons (60Co). C57BL/6 mice were exposed to 3 Gy (0.4 Gy/min) protons at spread-out Bragg peak (SOBP), protons at entry (E), or 60Co and euthanized on days 0.5-17 thereafter. 60Co-irradiated animals had decreased erythrocytes, hemoglobin and hematocrit at 12 hours post-exposure; depression was not noted in proton (SOBP or E)-irradiated groups until day 4. Significantly decreased leukocyte counts were observed at this same time in all irradiated groups, with lymphocyte loss being greater than that of monocytes, and the depression was generally maintained. In contrast, the levels of neutrophils and thrombocytes fluctuated, especially during the first week; significant differences were noted among irradiated groups in neutrophil levels. Plasma TGF-beta 1 was elevated on day 7 in the 60Co, but not proton, irradiated mice. Collectively, the data show that dramatic and persistent changes occurred in all irradiated groups. However, few differences in assay results were seen between animals exposed to protons (SOBP or E) or photons, as well as between the groups irradiated with either of the two regions of the proton Bragg curve.

  10. RBE and OER within the spread-out Bragg peak for proton beam therapy: in vitro study at the Proton Medical Research Center at the University of Tsukuba

    PubMed Central

    Kanemoto, Ayae; Hirayama, Ryoichi; Moritake, Takashi; Furusawa, Yoshiya; Sun, Lue; Sakae, Takeji; Kuno, Akihiro; Terunuma, Toshiyuki; Yasuoka, Kiyoshi; Mori, Yutaro; Tsuboi, Koji; Sakurai, Hideyuki

    2014-01-01

    There are few reports on the biological homogeneity within the spread-out Bragg peak (SOBP) of proton beams. Therefore, to evaluate the relative biological effectiveness (RBE) and the oxygen enhancement ratio (OER), human salivary gland tumor (HSG) cells were irradiated at the plateau position (position A) and three different positions within a 6-cm-wide SOBP (position B, 26 mm proximal to the middle; position C, middle; position D, 26 mm distal to the middle) using 155-MeV/n proton beams under both normoxic and hypoxic conditions at the Proton Medical Research Center, University of Tsukuba, Japan. The RBE to the plateau region (RBEplateau) and the OER value were calculated from the doses corresponding to 10% survival data. Under the normoxic condition, the RBEplateau was 1.00, 0.99 and 1.09 for positions B, C and D, respectively. Under the hypoxic condition, the RBEplateau was 1.10, 1.06 and 1.12 for positions B, C and D, respectively. The OER was 2.84, 2.60, 2.63 and 2.76 for positions A, B, C and D, respectively. There were no significant differences in either the RBEplateau or the OER between these three positions within the SOBP. In conclusion, biological homogeneity need not necessarily be taken into account for treatment planning for proton beam therapy at the University of Tsukuba. PMID:24876271

  11. Early elective cesarean delivery before 36 weeks vs late spontaneous delivery in infants with gastroschisis.

    PubMed

    Hadidi, Ahmed; Subotic, Ulrike; Goeppl, Maximilian; Waag, Karl-L

    2008-07-01

    The aim of this study is to assess the value of early elective cesarean delivery for patients with gastroschisis in comparison with late spontaneous delivery. Analysis of infants with gastroschisis admitted between 1986 and 2006 at a tertiary care center was performed. The findings were analyzed statistically. Eighty-six patients were involved in the study. This included 15 patients who underwent emergency cesarean delivery (EM CD group) because of fetal distress and/or bowel ischemia. The remaining 71 patients born electively were stratified into 4 groups. The early elective cesarean delivery (ECD) group included 23 patients born by ECD before 36 weeks; late vaginal delivery (LVD) group included 23 patients who had LVD after 36 weeks; 24 patients had LCD after 36 weeks because of delayed diagnosis that resulted in late referral; and 1 patient had early spontaneous vaginal delivery (EVD group) before 36 weeks. The mean time to start oral feeding, incidence of complications, and primary closure were significantly better in the ECD group than in the LVD group. The duration of ventilation and the length of stay were shorter in ECD group, but the difference was not statistically significant. Elective cesarean delivery before 36 weeks allows earlier enteral feeding and is associated with less complications and higher incidence of primary closure (statistically significant).

  12. Obtaining Accurate Probabilities Using Classifier Calibration

    ERIC Educational Resources Information Center

    Pakdaman Naeini, Mahdi

    2016-01-01

    Learning probabilistic classification and prediction models that generate accurate probabilities is essential in many prediction and decision-making tasks in machine learning and data mining. One way to achieve this goal is to post-process the output of classification models to obtain more accurate probabilities. These post-processing methods are…

  13. Approaching system equilibrium with accurate or not accurate feedback information in a two-route system

    NASA Astrophysics Data System (ADS)

    Zhao, Xiao-mei; Xie, Dong-fan; Li, Qi

    2015-02-01

    With the development of intelligent transport system, advanced information feedback strategies have been developed to reduce traffic congestion and enhance the capacity. However, previous strategies provide accurate information to travelers and our simulation results show that accurate information brings negative effects, especially in delay case. Because travelers prefer to the best condition route with accurate information, and delayed information cannot reflect current traffic condition but past. Then travelers make wrong routing decisions, causing the decrease of the capacity and the increase of oscillations and the system deviating from the equilibrium. To avoid the negative effect, bounded rationality is taken into account by introducing a boundedly rational threshold BR. When difference between two routes is less than the BR, routes have equal probability to be chosen. The bounded rationality is helpful to improve the efficiency in terms of capacity, oscillation and the gap deviating from the system equilibrium.

  14. Drug delivery.

    PubMed

    Le Souëf, Peter N

    2002-09-16

    What we know: In preschool children, small-volume spacers perform better than large-volume spacers. Detergent is the best antistatic agent for spacers, increasing lung delivery two- to threefold, but it must not be rinsed off. A mouthpiece should be used in children aged 2-3 years or older, as lung delivery is two- to threefold higher for oral inhalation than nasal inhalation (ie, by mask). Inhaled drug doses do not generally need to be reduced in infants and young children owing to inefficiencies of delivery in younger patients. Nebulisers are "dinosaurs" and not needed for most children with asthma. What we need to know: What is the best inhalation technique for spacers? How long should children breathe, how many breaths should they take, and at what age should they breath-hold? How should children, parents and doctors be instructed to achieve optimal levels of electrostatic charge reduction for spacers? How much should inhaled steroid dose be reduced when a spacer is used optimally? What dosing instructions should be given for beta(2)-agonists delivered by spacer?

  15. The potential of toxin-based drug delivery systems for enhanced nucleic acid therapeutic delivery.

    PubMed

    Shorter, Susan A; Gollings, Alexander S; Gorringe-Pattrick, Monique A M; Coakley, J Emma; Dyer, Paul D R; Richardson, Simon C W

    2017-05-01

    The potential of gene replacement therapy has been underscored by the market authorization of alipogene tiparvovec (Glybera) and GSK2696273 (Strimvelis) in the EU and recombinant adenovirus-p53 (Gendicine) in China. Common to these systems is the use of attenuated viruses for 'drug' delivery. Whilst viral delivery systems are being developed for siRNA, their application to antisense delivery remains problematic. Non-viral delivery remains experimental, with some notable successes. However, stability and the 'PEG dilemma', balancing toxicity and limited (often liver-tropic) pharmacokinetics/oharmacodynamics, with the membrane destabilizing activity, necessary for nucleocytosolic access and transfection remain a problem. Areas covered: Here we review the use of attenuated protein toxins as a delivery vehicle for nucleic acids, their relationship to the PEG dilemma, and their biological properties with specific reference to their intracellular trafficking. Expert opinion: The possibility of using attenuated toxins as antisense and siRNA delivery systems has been demonstrated in vitro. Systems based upon attenuated anthrax toxin have been shown to have high activity (equivalent to nucleofection) and low toxicity whilst not requiring cationic 'helpers' or condensing agents, divorcing these systems from the problems associated with the PEG dilemma. It remains to be seen whether these systems can operate safely, efficiently and reproducibly, in vivo or in the clinic.

  16. A Taxonomy of Delivery and Documentation Deviations During Delivery of High-Fidelity Simulations.

    PubMed

    McIvor, William R; Banerjee, Arna; Boulet, John R; Bekhuis, Tanja; Tseytlin, Eugene; Torsher, Laurence; DeMaria, Samuel; Rask, John P; Shotwell, Matthew S; Burden, Amanda; Cooper, Jeffrey B; Gaba, David M; Levine, Adam; Park, Christine; Sinz, Elizabeth; Steadman, Randolph H; Weinger, Matthew B

    2017-02-01

    We developed a taxonomy of simulation delivery and documentation deviations noted during a multicenter, high-fidelity simulation trial that was conducted to assess practicing physicians' performance. Eight simulation centers sought to implement standardized scenarios over 2 years. Rules, guidelines, and detailed scenario scripts were established to facilitate reproducible scenario delivery; however, pilot trials revealed deviations from those rubrics. A taxonomy with hierarchically arranged terms that define a lack of standardization of simulation scenario delivery was then created to aid educators and researchers in assessing and describing their ability to reproducibly conduct simulations. Thirty-six types of delivery or documentation deviations were identified from the scenario scripts and study rules. Using a Delphi technique and open card sorting, simulation experts formulated a taxonomy of high-fidelity simulation execution and documentation deviations. The taxonomy was iteratively refined and then tested by 2 investigators not involved with its development. The taxonomy has 2 main classes, simulation center deviation and participant deviation, which are further subdivided into as many as 6 subclasses. Inter-rater classification agreement using the taxonomy was 74% or greater for each of the 7 levels of its hierarchy. Cohen kappa calculations confirmed substantial agreement beyond that expected by chance. All deviations were classified within the taxonomy. This is a useful taxonomy that standardizes terms for simulation delivery and documentation deviations, facilitates quality assurance in scenario delivery, and enables quantification of the impact of deviations upon simulation-based performance assessment.

  17. Lifetime Increased Cancer Risk in Mice Following Exposure to Clinical Proton Beam–Generated Neutrons

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

    Gerweck, Leo E., E-mail: lgerweck@mgh.harvard.edu; Huang, Peigen; Lu, Hsiao-Ming

    2014-05-01

    Purpose: To evaluate the life span and risk of cancer following whole-body exposure of mice to neutrons generated by a passively scattered clinical spread-out Bragg peak (SOBP) proton beam. Methods and Materials: Three hundred young adult female FVB/N mice, 152 test and 148 control, were entered into the experiment. Mice were placed in an annular cassette around a cylindrical phantom, which was positioned lateral to the mid-SOBP of a 165-MeV, clinical proton beam. The average distance from the edge of the mid-SOBP to the conscious active mice was 21.5 cm. The phantom was irradiated with once-daily fractions of 25 Gy,more » 4 days per week, for 6 weeks. The age at death and cause of death (ie, cancer and type vs noncancer causes) were assessed over the life span of the mice. Results: Exposure of mice to a dose of 600 Gy of proton beam–generated neutrons, reduced the median life span of the mice by 4.2% (Kaplan-Meier cumulative survival, P=.053). The relative risk of death from cancer in neutron exposed versus control mice was 1.40 for cancer of all types (P=.0006) and 1.22 for solid cancers (P=.09). For a typical 60 Gy dose of clinical protons, the observed 22% increased risk of solid cancer would be expected to decrease by a factor of 10. Conclusions: Exposure of mice to neutrons generated by a proton dose that exceeds a typical course of radiation therapy by a factor of 10, resulted in a statistically significant increase in the background incidence of leukemia and a marginally significant increase in solid cancer. The results indicate that the risk of out-of-field second solid cancers from SOBP proton-generated neutrons and typical treatment schedules, is 6 to 10 times less than is suggested by current neutron risk estimates.« less

  18. Laser beam uniformity and stability using homogenizer-based fiber optic launch method: square core fiber delivery

    NASA Astrophysics Data System (ADS)

    Lizotte, Todd E.

    2011-03-01

    Over the years, technological achievements within the laser medical diagnostic, treatment, and therapy markets have led to ever increasing requirements for greater control of critical laser beam parameters. Increased laser power/energy stabilization, temporal and spatial beam shaping and flexible laser beam delivery systems with ergonomic focusing or imaging lens systems are sought by leading medical laser system producers. With medical procedures that utilize laser energy, there is a constant emphasis on reducing adverse effects that come about by the laser itself or its optical system, but even when these variables are well controlled the medical professional will still need to deal with the multivariate nature of the human body. Focusing on the variables that can be controlled, such as accurate placement of the laser beam where it will expose a surface being treated as well as laser beam shape and uniformity is critical to minimizing adverse conditions. This paper covers the use of fiber optic beam delivery as a means of defining the beam shape (intensity/power distribution uniformity) at the target plane as well as the use of fiber delivery as a means to allow more flexible articulation of the laser beam over the surface being treated. The paper will present a new concept of using a square core fiber beam delivery design utilizing a unique micro lens array (MLA) launch method that improves the overall stability of the system, by minimizing the impact of the laser instability. The resulting performance of the prototype is presented to demonstrate its stability in comparison to simple lens launch techniques, with an emphasis on homogenization and articulated fiber delivery.

  19. TH-A-9A-10: Prostate SBRT Delivery with Flattening-Filter-Free Mode: Benefit and Accuracy

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

    Li, T; Yuan, L; Sheng, Y

    Purpose: Flattening-filter-free (FFF) beam mode offered on TrueBeam™ linac enables delivering IMRT at 2400 MU/min dose rate. This study investigates the benefit and delivery accuracy of using high dose rate in the context of prostate SBRT. Methods: 8 prostate SBRT patients were retrospectively studied. In 5 cases treated with 600-MU/min dose rate, continuous prostate motion data acquired during radiation-beam-on was used to analyze motion range. In addition, the initial 1/3 of prostate motion trajectories during each radiation-beam-on was separated to simulate motion range if 2400-MU/min were used. To analyze delivery accuracy in FFF mode, MLC trajectory log files from anmore » additional 3 cases treated at 2400-MU/min were acquired. These log files record MLC expected and actual positions every 20ms, and therefore can be used to reveal delivery accuracy. Results: (1) Benefit. On average treatment at 600-MU/min takes 30s per beam; whereas 2400-MU/min requires only 11s. When shortening delivery time to ~1/3, the prostate motion range was significantly smaller (p<0.001). Largest motion reduction occurred in Sup-Inf direction, from [−3.3mm, 2.1mm] to [−1.7mm, 1.7mm], followed by reduction from [−2.1mm, 2.4mm] to [−1.0mm, 2.4mm] in Ant-Pos direction. No change observed in LR direction [−0.8mm, 0.6mm]. The combined motion amplitude (vector norm) confirms that average motion and ranges are significantly smaller when beam-on was limited to the 1st 1/3 of actual delivery time. (2) Accuracy. Trajectory log file analysis showed excellent delivery accuracy with at 2400 MU/min. Most leaf deviations during beam-on were within 0.07mm (99-percentile). Maximum leaf-opening deviations during each beam-on were all under 0.1mm for all leaves. Dose-rate was maintained at 2400-MU/min during beam-on without dipping. Conclusion: Delivery prostate SBRT with 2400 MU/min is both beneficial and accurate. High dose rates significantly reduced both treatment time and intra

  20. Advanced Drug Delivery Systems for Transdermal Delivery of Non-Steroidal Anti-Inflammatory Drugs: A Review.

    PubMed

    Kumar, Lalit; Verma, Shivani; Singh, Mehakjot; Tamanna, Tamanna; Utreja, Puneet

    2018-06-04

    Transdermal route of delivery of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) has several advantages over other routes like reduced adverse effects, less systemic absorption, and avoidance of first pass effect and degradation in the gastrointestinal tract (GIT). Transdermal route is also beneficial for drugs having a narrow therapeutic index. The skin acts as the primary barrier for transdermal delivery of various therapeutic molecules. Various advanced nanocarrier systems offer several advantages like improved dermal penetration along with an extended drug release profile due to their smaller size and high surface area. Various nanocarrier explored for transdermal delivery of NSAIDs are liposomes, niosomes, ethosomes, polymeric nanoparticles (NPs), solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), dendrimers, nanosuspensions/nanoemulsion, and nanofibers Objectives: In the present review, our major aim was to explore the therapeutic potential of advanced nanocarrier systems enlisted above for transdermal delivery of NSAIDs. All literature search regarding advanced nanocarrier systems for transdermal delivery of NSAIDs was done using Google Scholar and Pubmed. Advanced nanocarrier have shown various advantages like reduced side effect, low dosing frequency, high skin permeation, and ease of application over conventional transdermal delivery systems of NSAIDs in various preclinical studies. However, clinical exploration of advanced nanocarrier systems for transdermal delivery of NSAIDs is still a challenge. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Microfabrication for Drug Delivery

    PubMed Central

    Koch, Brendan; Rubino, Ilaria; Quan, Fu-Shi; Yoo, Bongyoung; Choi, Hyo-Jick

    2016-01-01

    This review is devoted to discussing the application of microfabrication technologies to target challenges encountered in life processes by the development of drug delivery systems. Recently, microfabrication has been largely applied to solve health and pharmaceutical science issues. In particular, fabrication methods along with compatible materials have been successfully designed to produce multifunctional, highly effective drug delivery systems. Microfabrication offers unique tools that can tackle problems in this field, such as ease of mass production with high quality control and low cost, complexity of architecture design and a broad range of materials. Presented is an overview of silicon- and polymer-based fabrication methods that are key in the production of microfabricated drug delivery systems. Moreover, the efforts focused on studying the biocompatibility of materials used in microfabrication are analyzed. Finally, this review discusses representative ways microfabrication has been employed to develop systems delivering drugs through the transdermal and oral route, and to improve drug eluting implants. Additionally, microfabricated vaccine delivery systems are presented due to the great impact they can have in obtaining a cold chain-free vaccine, with long-term stability. Microfabrication will continue to offer new, alternative solutions for the development of smart, advanced drug delivery systems. PMID:28773770

  2. Redefining global health-care delivery.

    PubMed

    Kim, Jim Yong; Farmer, Paul; Porter, Michael E

    2013-09-21

    Initiatives to address the unmet needs of those facing both poverty and serious illness have expanded significantly over the past decade. But many of them are designed in an ad-hoc manner to address one health problem among many; they are too rarely assessed; best practices spread slowly. When assessments of delivery do occur, they are often narrow studies of the cost-effectiveness of a single intervention rather than the complex set of them required to deliver value to patients and their families. We propose a framework for global health-care delivery and evaluation by considering efforts to introduce HIV/AIDS care to resource-poor settings. The framework introduces the notion of care delivery value chains that apply a systems-level analysis to the complex processes and interventions that must occur, across a health-care system and over time, to deliver high-value care for patients with HIV/AIDS and cooccurring conditions, from tuberculosis to malnutrition. To deliver value, vertical or stand-alone projects must be integrated into shared delivery infrastructure so that personnel and facilities are used wisely and economies of scale reaped. Two other integrative processes are necessary for delivering and assessing value in global health: one is the alignment of delivery with local context by incorporating knowledge of both barriers to good outcomes (from poor nutrition to a lack of water and sanitation) and broader social and economic determinants of health and wellbeing (jobs, housing, physical infrastructure). The second is the use of effective investments in care delivery to promote equitable economic development, especially for those struggling against poverty and high burdens of disease. We close by reporting our own shared experience of seeking to move towards a science of delivery by harnessing research and training to understand and improve care delivery. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Visualization and tracking of tumour extracellular vesicle delivery and RNA translation using multiplexed reporters

    PubMed Central

    Lai, Charles P.; Kim, Edward Y.; Badr, Christian E.; Weissleder, Ralph; Mempel, Thorsten R.; Tannous, Bakhos A.; Breakefield, Xandra O.

    2015-01-01

    Accurate spatiotemporal assessment of extracellular vesicle (EV) delivery and cargo RNA translation requires specific and robust live-cell imaging technologies. Here we engineer optical reporters to label multiple EV populations for visualization and tracking of tumour EV release, uptake and exchange between cell populations both in culture and in vivo. Enhanced green fluorescence protein (EGFP) and tandem dimer Tomato (tdTomato) were fused at NH2-termini with a palmitoylation signal (PalmGFP, PalmtdTomato) for EV membrane labelling. To monitor EV-RNA cargo, transcripts encoding PalmtdTomato were tagged with MS2 RNA binding sequences and detected by co-expression of bacteriophage MS2 coat protein fused with EGFP. By multiplexing fluorescent and bioluminescent EV membrane reporters, we reveal the rapid dynamics of both EV uptake and translation of EV-delivered cargo mRNAs in cancer cells that occurred within 1-hour post-horizontal transfer between cells. These studies confirm that EV-mediated communication is dynamic and multidirectional between cells with delivery of functional mRNA. PMID:25967391

  4. Ultrasound mediated transdermal drug delivery.

    PubMed

    Azagury, Aharon; Khoury, Luai; Enden, Giora; Kost, Joseph

    2014-06-01

    Transdermal drug delivery offers an attractive alternative to the conventional drug delivery methods of oral administration and injections. However, the stratum corneum serves as a barrier that limits the penetration of substances to the skin. Application of ultrasound (US) irradiation to the skin increases its permeability (sonophoresis) and enables the delivery of various substances into and through the skin. This review presents the main findings in the field of sonophoresis in transdermal drug delivery as well as transdermal monitoring and the mathematical models associated with this field. Particular attention is paid to the proposed enhancement mechanisms and future trends in the fields of cutaneous vaccination and gene therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Protein-Based Nanomedicine Platforms for Drug Delivery

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

    Ma Ham, Aihui; Tang, Zhiwen; Wu, Hong

    2009-08-03

    Drug delivery systems have been developed for many years, however some limitations still hurdle the pace of going to clinical phase, for example, poor biodistribution, drug molecule cytotoxicity, tissue damage, quick clearance from the circulation system, solubility and stability of drug molecules. To overcome the limitations of drug delivery, biomaterials have to be developed and applied to drug delivery to protect the drug molecules and to enhance the drug’s efficacy. Protein-based nanomedicine platforms for drug delivery are platforms comprised of naturally self-assembled protein subunits of the same protein or a combination of proteins making up a complete system. They aremore » ideal for drug delivery platforms due to their biocompatibility and biodegradability coupled with low toxicity. A variety of proteins have been used and characterized for drug delivery systems including the ferritin/apoferritin protein cage, plant derived viral capsids, the small Heat shock protein (sHsp) cage, albumin, soy and whey protein, collagen, and gelatin. There are many different types and shapes that have been prepared to deliver drug molecules using protein-based platforms including the various protein cages, microspheres, nanoparticles, hydrogels, films, minirods and minipellets. There are over 30 therapeutic compounds that have been investigated with protein-based drug delivery platforms for the potential treatment of various cancers, infectious diseases, chronic diseases, autoimmune diseases. In protein-based drug delivery platforms, protein cage is the most newly developed biomaterials for drug delivery and therapeutic applications. Their uniform sizes, multifunctions, and biodegradability push them to the frontier for drug delivery. In this review, the recent strategic development of drug delivery has been discussed with a special emphasis upon the polymer based, especially protein-based nanomedicine platforms for drug delivery. The advantages and disadvantages are

  6. Fiber coupled optical spark delivery system

    DOEpatents

    Yalin, Azer; Willson, Bryan; Defoort, Morgan

    2008-08-12

    A spark delivery system for generating a spark using a laser beam is provided, the spark delivery system including a laser light source and a laser delivery assembly. The laser delivery assembly includes a hollow fiber and a launch assembly comprising launch focusing optics to input the laser beam in the hollow fiber. In addition, the laser delivery assembly includes exit focusing optics that demagnify an exit beam of laser light from the hollow fiber, thereby increasing the intensity of the laser beam and creating a spark. In accordance with embodiments of the present invention, the assembly may be used to create a spark in a combustion engine. In accordance with other embodiments of the present invention, a method of using the spark delivery system is provided. In addition, a method of choosing an appropriate fiber for creating a spark using a laser beam is also presented.

  7. Controlled-release, pegylation, liposomal formulations: new mechanisms in the delivery of injectable drugs.

    PubMed

    Reddy, K R

    2000-01-01

    To review recent developments in novel injectable drug delivery mechanisms and outline the advantages and disadvantages of each. A MEDLINE (1995-January 2000) search using the terms polyethylene glycol, liposomes, polymers, polylactic acid, and controlled release was conducted. Additional references were identified by scanning bibliographies. All articles were considered for inclusion. Abstracts were included only if they were judged to add critical information not otherwise available in the medical literature. A number of systems that alter the delivery of injectable drugs have been developed in attempts to improve pharmacodynamic and pharmacokinetic properties of therapeutic agents. New drug delivery systems can be produced either through a change in formulation (e.g., continuous-release products, liposomes) or an addition to the drug molecule (e.g., pegylation). Potential advantages of new delivery mechanisms include an increased or prolonged duration of pharmacologic activity, a decrease in adverse effects, and increased patient compliance and quality of life. Injectable continuous-release systems deliver drugs in a controlled, predetermined fashion and are particularly appropriate when it is important to avoid large fluctuations in plasma drug concentrations. Encapsulating a drug within a liposome can produce a prolonged half-life and a shift of distribution toward tissues with increased capillary permeability (e.g., tumors, infected tissue). Pegylation provides a method for modification of therapeutic proteins to minimize many of the limitations (e.g., poor stability, short half-life, immunogenicity) associated with these agents. Pegylation of therapeutic proteins is an established process with new applications. However, not all pegylated proteins are alike, and each requires optimization on a protein-by-protein basis to derive maximum clinical benefit. The language required to describe each pegylated therapeutic protein must be more precise to accurately

  8. Family-Centered Service Delivery.

    ERIC Educational Resources Information Center

    Higgins, Cindy, Ed.

    1997-01-01

    This theme issue focuses on family-centered practices and policies for service delivery. The first article, "Family-Centered Service Delivery," reports on a study of 130 published sources in education, social work, nursing, psychology, occupational therapy, and related disciplines, which found that the key components of family-centered…

  9. Polypeptides and polyaminoacids in drug delivery.

    PubMed

    González-Aramundiz, José Vicente; Lozano, María Victoria; Sousa-Herves, Ana; Fernandez-Megia, Eduardo; Csaba, Noemi

    2012-02-01

    Advances achieved over the last few years in drug delivery have provided novel and versatile possibilities for the treatment of various diseases. Among the biomaterials applied in this field, it is worth highlighting the increasing importance of polyaminoacids and polypeptides. The appealing properties of these polymers are very promising for the design of novel compositions in a variety of drug delivery applications. This review provides an overview on the general characteristics of polyaminoacids and polypeptides and briefly discusses different synthetic pathways for their production. This is followed by a detailed description of different drug delivery applications of these polymers, emphasizing those examples that already reached advanced preclinical development or have entered clinical trials. Polyaminoacids and polypeptides are gaining much attention in drug delivery due to their exceptional properties. Their application as polymers for drug delivery purposes has been sped up by the significant achievements related to their synthesis. Certainly, cancer therapy has benefited the most from these advances, although other fields such as vaccine delivery and alternative administration routes are also being successfully explored. The design of new entities based on polyaminoacids and polypeptides and the improved insight gained in drug delivery guarantee exciting findings in the near future.

  10. 3D Monte Carlo model with direct photon flux recording for optimal optogenetic light delivery

    NASA Astrophysics Data System (ADS)

    Shin, Younghoon; Kim, Dongmok; Lee, Jihoon; Kwon, Hyuk-Sang

    2017-02-01

    Configuring the light power emitted from the optical fiber is an essential first step in planning in-vivo optogenetic experiments. However, diffusion theory, which was adopted for optogenetic research, precluded accurate estimates of light intensity in the semi-diffusive region where the primary locus of the stimulation is located. We present a 3D Monte Carlo model that provides an accurate and direct solution for light distribution in this region. Our method directly records the photon trajectory in the separate volumetric grid planes for the near-source recording efficiency gain, and it incorporates a 3D brain mesh to support both homogeneous and heterogeneous brain tissue. We investigated the light emitted from optical fibers in brain tissue in 3D, and we applied the results to design optimal light delivery parameters for precise optogenetic manipulation by considering the fiber output power, wavelength, fiber-to-target distance, and the area of neural tissue activation.

  11. Ultrasound-guided drug delivery in cancer

    PubMed Central

    2017-01-01

    Recent advancements in ultrasound and microbubble (USMB) mediated drug delivery technology has shown that this approach can improve spatially confined delivery of drugs and genes to target tissues while reducing systemic dose and toxicity. The mechanism behind enhanced delivery of therapeutics is sonoporation, the formation of openings in the vasculature, induced by ultrasound-triggered oscillations and destruction of microbubbles. In this review, progress and challenges of USMB mediated drug delivery are summarized, with special focus on cancer therapy. PMID:28607323

  12. Patterns of Recovery from Pain after Cesarean Delivery.

    PubMed

    Booth, Jessica L; Sharpe, Emily E; Houle, Timothy T; Harris, Lynnette; Curry, Regina S; Aschenbrenner, Carol A; Eisenach, James C

    2018-06-13

    We know very little about the change in pain in the first 2 months after surgery. To address this gap, we studied 530 women scheduled for elective cesarean delivery who completed daily pain diaries for two months after surgery via text messaging. Over 82% of subjects missed fewer than 10 diary entries and were included in the analysis. Completers were more likely to be Caucasian, non-smokers, and with fewer previous pregnancies than non-completers. Daily worst pain intensity ratings for the previous 24 hours were fit to a log(time) function and allowed to change to a different function up to 3 times according to a Bayesian criterion. All women had at least one change point, occurring 22 ± 9 days postoperatively, and 81% of women had only one change, most commonly to a linear function at 0 pain. Approximately 9% of women were predicted to have pain 2 months after surgery, similar to previous observations. Cluster analysis revealed 6 trajectories of recovery from pain. Predictors of cluster membership included severity of acute pain, perceived stress, surgical factors, and smoking status. These data demonstrate feasibility but considerable challenges to this approach to data acquisition. The form of the initial process of recovery from pain is common to all women, with divergence of patterns at 2-4 weeks after cesarean delivery. The change point model accurately predicts recovery from pain, its parameters can be used to assess predictors of speed of recovery, and it may be useful for future observational, forecasting, and interventional trials.

  13. A novel individual-cell-based mathematical model based on multicellular tumour spheroids for evaluating doxorubicin-related delivery in avascular regions.

    PubMed

    Liu, Jiali; Yan, Fangrong; Chen, Hongzhu; Wang, Wenjie; Liu, Wenyue; Hao, Kun; Wang, Guangji; Zhou, Fang; Zhang, Jingwei

    2017-09-01

    Effective drug delivery in the avascular regions of tumours, which is crucial for the promising antitumour activity of doxorubicin-related therapy, is governed by two inseparable processes: intercellular diffusion and intracellular retention. To accurately evaluate doxorubicin-related delivery in the avascular regions, these two processes should be assessed together. Here we describe a new approach to such an assessment. An individual-cell-based mathematical model based on multicellular tumour spheroids was developed that describes the different intercellular diffusion and intracellular retention kinetics of doxorubicin in each cell layer. The different effects of a P-glycoprotein inhibitor (LY335979) and a hypoxia inhibitor (YC-1) were quantitatively evaluated and compared, in vitro (tumour spheroids) and in vivo (HepG2 tumours in mice). This approach was further tested by evaluating in these models, an experimental doxorubicin derivative, INNO 206, which is in Phase II clinical trials. Inhomogeneous, hypoxia-induced, P-glycoprotein expression compromised active transport of doxorubicin in the central area, that is, far from the vasculature. LY335979 inhibited efflux due to P-glycoprotein but limited levels of doxorubicin outside the inner cells, whereas YC-1 co-administration specifically increased doxorubicin accumulation in the inner cells without affecting the extracellular levels. INNO 206 exhibited a more effective distribution profile than doxorubicin. The individual-cell-based mathematical model accurately evaluated and predicted doxorubicin-related delivery and regulation in the avascular regions of tumours. The described framework provides a mechanistic basis for the proper development of doxorubicin-related drug co-administration profiles and nanoparticle development and could avoid unnecessary clinical trials. © 2017 The British Pharmacological Society.

  14. Microspheres and Nanotechnology for Drug Delivery.

    PubMed

    Jóhannesson, Gauti; Stefánsson, Einar; Loftsson, Thorsteinn

    2016-01-01

    Ocular drug delivery to the posterior segment of the eye can be accomplished by invasive drug injections into different tissues of the eye and noninvasive topical treatment. Invasive treatment involves the risks of surgical trauma and infection, and conventional topical treatments are ineffective in delivering drugs to the posterior segment of the eye. In recent years, nanotechnology has become an ever-increasing part of ocular drug delivery. In the following, we briefly review microspheres and nanotechnology for drug delivery to the eye, including different forms of nanotechnology such as nanoparticles, microparticles, liposomes, microemulsions and micromachines. The permeation barriers and anatomical considerations linked to ocular drug delivery are discussed and a theoretical overview on drug delivery through biological membranes is given. Finally, in vitro, in vivo and human studies of x03B3;-cyclodextrin nanoparticle eyedrop suspensions are discussed as an example of nanotechnology used for drug delivery to the eye. © 2016 S. Karger AG, Basel.

  15. Route of delivery following successful external cephalic version.

    PubMed

    Policiano, Catarina; Costa, Ana; Valentim-Lourenço, Alexandre; Clode, Nuno; Graça, Luís M

    2014-09-01

    To evaluate the delivery route and the indications for cesarean delivery after successful external cephalic version (ECV). A retrospective matched case-control study was conducted at a hospital in Lisbon, Portugal, between 2002 and 2012. Each woman who underwent successful ECV (n = 44) was compared with the previous and next women who presented for labor management and who had the same parity and a singleton vertex pregnancy at term (n = 88). The outcome measures were route of delivery, indications for cesarean delivery, and incidence of nonreassuring fetal status. Attempts at ECV were successful in 62 (46%) of 134 women, and 44 women whose fetuses remained in a cephalic presentation until delivery were included in the study. The rates of intrapartum cesarean delivery and operative vaginal delivery did not differ significantly between cases and controls (intrapartum cesarean delivery, 9 [20%] vs 16 [18%], P = 0.75; operative vaginal delivery, 14 [32%] vs 19 [22%], P = 0.20). The indications for cesarean delivery after successful ECV did not differ; in both groups, cesarean delivery was mainly performed for labor arrest disorders (cases, 6 [67%] vs controls, 13 [81%]; P = 0.63). Successful ECV was not associated with increased rates of intrapartum cesarean delivery or operative vaginal delivery. Copyright © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  16. Oral delivery of peptides and proteins using lipid-based drug delivery systems.

    PubMed

    Li, Ping; Nielsen, Hanne Mørck; Müllertz, Anette

    2012-10-01

    In order to successfully develop lipid-based drug delivery systems (DDS) for oral administration of peptides and proteins, it is important to gain an understanding of the colloid structures formed by these DDS, the mode of peptide and protein incorporation as well as the mechanism by which intestinal absorption of peptides and proteins is promoted. The present paper reviews the literature on lipid-based DDS, employed for oral delivery of peptides and proteins and highlights the mechanisms by which the different lipid-based carriers are expected to overcome the two most important barriers (extensive enzymatic degradation and poor transmucosal permeability). This paper also gives a clear-cut idea about advantages and drawbacks of using different lipidic colloidal carriers ((micro)emulsions, solid lipid core particles and liposomes) for oral delivery of peptides and proteins. Lipid-based DDS are safe and suitable for oral delivery of peptides and proteins. Significant progress has been made in this area with several technologies on clinical trials. However, a better understanding of the mechanism of action in vivo is needed in order to improve the design and development of lipid-based DDS with the desired bioavailability and therapeutic profile.

  17. Accuracy of pulse oximetry measurement of heart rate of newborn infants in the delivery room.

    PubMed

    Kamlin, C Omar F; Dawson, Jennifer A; O'Donnell, Colm P F; Morley, Colin J; Donath, Susan M; Sekhon, Jasbir; Davis, Peter G

    2008-06-01

    To determine the accuracy of heart rate obtained by pulse oximetry (HR(PO)) relative to HR obtained by 3-lead electrocardiography (HR(ECG)) in newborn infants in the delivery room. Immediately after birth, a preductal PO sensor and ECG leads were applied. PO and ECG monitor displays were recorded by a video camera. Two investigators reviewed the videos. Every two seconds, 1 of the investigators recorded HR(PO) and indicators of signal quality from the oximeter while masked to ECG, whereas the other recorded HR(ECG) and ECG signal quality while masked to PO. HR(PO) and HR(ECG) measurements were compared using Bland-Altman analysis. We attended 92 deliveries; 37 infants were excluded due to equipment malfunction. The 55 infants studied had a mean (+/-standard deviation [SD]) gestational age of 35 (+/-3.7) weeks, and birth weight 2399 (+/-869) g. In total, we analyzed 5877 data pairs. The mean difference (+/-2 SD) between HR(ECG) and HR(PO) was -2 (+/-26) beats per minute (bpm) overall and -0.5 (+/-16) bpm in those infants who received positive-pressure ventilation and/or cardiac massage. The sensitivity and specificity of PO for detecting HR(ECG) <100 bpm was 89% and 99%, respectively. PO provided an accurate display of newborn infants' HR in the delivery room, including those infants receiving advanced resuscitation.

  18. Water soluble nanoporous nanoparticle for in vivo targeted drug delivery and controlled release in B cells tumor context

    NASA Astrophysics Data System (ADS)

    de Angelis, F.; Pujia, A.; Falcone, C.; Iaccino, E.; Palmieri, C.; Liberale, C.; Mecarini, F.; Candeloro, P.; Luberto, L.; de Laurentiis, A.; Das, G.; Scala, G.; di Fabrizio, E.

    2010-10-01

    Multitasking nanoparticles are gaining great attention for smart drug delivery systems. The exploration of the nano-scale opens new concrete opportunities for revealing new properties and undiscovered cell-particle interactions. Here we present a biodegradable nanoporous silicon nanoparticle that can be successfully employed for in vivo targeted drug delivery and sustained release. The bare nanoporous nanocarriers can be accurately designed and fabricated with an effective control of porosity, surface chemistry and particle size, up to a few nm. The proposed nanoparticles exhibit several remarkable features including high payload, biodegradability, no toxicity, and multiple loading in water without the need of additional chemical reagents at room temperature. The targeting strategy is based on phage display technology that was successfully used to discover cell surface binding peptide for murine B lymphoma A20 cell line. The peptide used in combination with the nanoporous nanoparticles allows an efficient in vivo targeting, a sustained release and a sensible therapeutic effect.Multitasking nanoparticles are gaining great attention for smart drug delivery systems. The exploration of the nano-scale opens new concrete opportunities for revealing new properties and undiscovered cell-particle interactions. Here we present a biodegradable nanoporous silicon nanoparticle that can be successfully employed for in vivo targeted drug delivery and sustained release. The bare nanoporous nanocarriers can be accurately designed and fabricated with an effective control of porosity, surface chemistry and particle size, up to a few nm. The proposed nanoparticles exhibit several remarkable features including high payload, biodegradability, no toxicity, and multiple loading in water without the need of additional chemical reagents at room temperature. The targeting strategy is based on phage display technology that was successfully used to discover cell surface binding peptide for

  19. Assessment of the adequacy of oxygen delivery.

    PubMed

    Mayer, Katherine; Trzeciak, Stephen; Puri, Nitin K

    2016-10-01

    This article reviews the recent literature pertaining to assessment of the adequacy of oxygen delivery in critically ill patients with circulatory shock. The assessment of the adequacy of oxygen delivery has traditionally involved measurement of lactate, central (or mixed) venous oxygen saturation (ScvO2), and global hemodynamic markers such as mean arterial pressure and cardiac index. The search for noninvasive, reliable, and sensitive methods to detect derangements in oxygen delivery and utilization continues. Recent studies focus on near-infrared spectroscopy (NIRS) to assess regional tissue oxygenation, as well as bedside ultrasound techniques to assess the macrovascular hemodynamic factors in oxygen delivery. In this article, we review physiologic principles of global oxygen delivery, and discuss the bedside approach to assessing the adequacy of oxygen delivery in critically ill patients. Although there have been technological advances in the assessment of oxygen delivery, we revisit and emphasize the importance of a 'tried and true' method - the physical examination. Also potentially important in the evaluation of oxygen delivery is the utilization of biomarkers (e.g., lactate, ScvO2, NIRS). In complementary fashion, bedside ultrasound for hemodynamic assessment may augment the physical examination and biomarkers, and represents a potentially important adjunct for assessing the adequacy of oxygen delivery.

  20. [Risk factors associated with dystocic delivery].

    PubMed

    Romero Gutiérrez, Gustavo; Ríos López, Juan Carlos; Cortés Salim, Patricia; Ponce Ponce de León, Ana Lilia

    2007-09-01

    the dystocic delivery is a frequent complication and its perinatal repercussions vary from minor lesions to severe brain damage. It has been reported diverse factors associated with this medical complication. to identify the risk factors with significant association with dystocic delivery. a case-control study was carried out. There were included 750 patients, divided into 250 women with dystocic deliveries (cases) and 500 women with eutocic deliveries (controls). Demographic and clinical variables were registered. The statistical analysis was performed with percentages, arithmetic media, standard deviation, Student t test, chi2 and logistic regression analysis. An alpha value was set at 0.05. the factors with statistical significance were: advanced age (p < 0.001), major patient's height (p < 0.001), major new born's weight (p = 0.009), lower parity (p < 0.001), and prolonged duration of labor (p = 0.04). Other variables such as number of pregnancies, previous cesarean sections, spontaneous abortions, weight of the patient, weight earned during pregnancy, number of medical appointments during antenatal care, previous dystocic delivery, and premature rupture of the membranes, were not significant. there are clinical and demographic risk factors associated with dystocic delivery. To identify this risk factors during the antenatal care could diminish the frequency of dystocic deliveries and therefore to avoid the associated maternal-fetal complications.

  1. 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.

  2. 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

  3. Drug delivery across length scales.

    PubMed

    Delcassian, Derfogail; Patel, Asha K; Cortinas, Abel B; Langer, Robert

    2018-02-20

    Over the last century, there has been a dramatic change in the nature of therapeutic, biologically active molecules available to treat disease. Therapies have evolved from extracted natural products towards rationally designed biomolecules, including small molecules, engineered proteins and nucleic acids. The use of potent drugs which target specific organs, cells or biochemical pathways, necessitates new tools which can enable controlled delivery and dosing of these therapeutics to their biological targets. Here, we review the miniaturisation of drug delivery systems from the macro to nano-scale, focussing on controlled dosing and controlled targeting as two key parameters in drug delivery device design. We describe how the miniaturisation of these devices enables the move from repeated, systemic dosing, to on-demand, targeted delivery of therapeutic drugs and highlight areas of focus for the future.

  4. Relative biological effectiveness of the 60-MeV therapeutic proton beam at the Institute of Nuclear Physics (IFJ PAN) in Kraków, Poland.

    PubMed

    Słonina, Dorota; Biesaga, Beata; Swakoń, Jan; Kabat, Damian; Grzanka, Leszek; Ptaszkiewicz, Marta; Sowa, Urszula

    2014-11-01

    The aim of the study was to determine the relative biological effectiveness (RBE) of a 60-MeV proton radiotherapy beam at the Institute of Nuclear Physics, Polish Academy of Sciences (IFJ PAN) in Kraków, the first one to operate in Poland. RBE was assessed at the surviving fractions (SFs) of 0.01, 0.1, and 0.37, for normal human fibroblasts from three cancer patients. The cells were irradiated near the Bragg peak of the pristine beam and at three depths within a 28.4-mm spread-out Bragg peak (SOBP). Reference radiation was provided by 6-MV X-rays. The mean RBE value at SF = 0.01 for fibroblasts irradiated near the Bragg peak of pristine beam ranged between 1.06 and 1.15. The mean RBE values at SF = 0.01 for these cells exposed at depths of 2, 15, and 27 mm of the SOBP ranged between 0.95-1.00, 0.97-1.02, and 1.05-1.11, respectively. A trend was observed for RBE values to increase with survival level and with depth in the SOBP: at SF = 0.37 and at the depth of 27 mm, RBE values attained their maximum (1.19-1.24). The RBE values estimated at SF = 0.01 using normal human fibroblasts for the 60-MeV proton radiotherapy beam at the IFJ PAN in Kraków are close to values of 1.0 and 1.1, used in clinical practice.

  5. [Bacterial vaginosis and preterm delivery risk].

    PubMed

    Milewicz, Tomasz; Hejnar, Janusz; Jach, Robert; Jaworowski, Andrzej P; Piskorz, Tomasz; Gach, Andrzej; Krzysiek, Józef

    2010-01-01

    The aim of the study was to evaluate the impact of early, second trimester bacterial vaginosis [BV] on the number of threatened preterm deliveries. Group A consisted of 52 pregnant women in whom BV was diagnosed in the beginning of the 2nd trimester of pregnancy. Group A patients were treated with a 10 day course of metronidazole 0.5 g vaginally daily. Group B consisted of 122 pregnant women without BV. The number of cases with threatened preterm delivery was prospectively assessed in both groups. There were 28 cases of threatened preterm delivery in group A (53.8%) and 6 similar cases in group B (4.9%) (p < 0.05--Chi square test d.f.1). All cases (n = 20) of BV at the time of hospitalization due to threatened preterm delivery occurred in group A. The cases of threatened preterm delivery occurred significantly more frequently in pregnant patients who had the BV diagnosed in the beginning of the 2nd trimester. This may suggest the link between BV and the occurrence of threatened preterm deliveries.

  6. [Beneficial effect of maternity leave on delivery].

    PubMed

    Xu, Qian; Séguin, Louise; Goulet, Lise

    2002-01-01

    To identify the contribution of the duration of the prenatal maternity leave on term delivery. Characteristics of the prenatal maternity leave and delivery among 363 working women who had delivered a full-term infant at 1 of 4 hospitals in Montreal during 1996 were studied. The presence of an intervention or complication during delivery was observed in 68.9% of the participants. The average duration of the prenatal maternity leave was about 8 weeks (SD = 7). The adjusted risk of a difficult delivery decreased significantly with the duration of the prenatal maternity leave (OR = 0.96; 95% CI: 0.93-0.99). The duration of the maternity leave before delivery is associated with an easier term delivery for working women.

  7. Permeation enhancer strategies in transdermal drug delivery.

    PubMed

    Marwah, Harneet; Garg, Tarun; Goyal, Amit K; Rath, Goutam

    2016-01-01

    Today, ∼74% of drugs are taken orally and are not found to be as effective as desired. To improve such characteristics, transdermal drug delivery was brought to existence. This delivery system is capable of transporting the drug or macromolecules painlessly through skin into the blood circulation at fixed rate. Topical administration of therapeutic agents offers many advantages over conventional oral and invasive techniques of drug delivery. Several important advantages of transdermal drug delivery are prevention from hepatic first pass metabolism, enhancement of therapeutic efficiency and maintenance of steady plasma level of the drug. Human skin surface, as a site of drug application for both local and systemic effects, is the most eligible candidate available. New controlled transdermal drug delivery systems (TDDS) technologies (electrically-based, structure-based and velocity-based) have been developed and commercialized for the transdermal delivery of troublesome drugs. This review article covers most of the new active transport technologies involved in enhancing the transdermal permeation via effective drug delivery system.

  8. Exploring the feasibility of alternative STD-testing venues and results delivery channels for a national screening campaign.

    PubMed

    Friedman, Allison L; Bloodgood, Bonny

    2013-01-01

    Annual chlamydia screening is recommended for sexually active women aged 25 years and younger, though less than half of eligible women are screened each year. If acceptable to young women, nontraditional testing venues and new communication technologies could promote efficiencies in sexually transmitted disease (STD) screening and facilitate screening by overcoming barriers at systems and patient levels. This study sought to explore young women's technology use, preferences for STD-testing venues, attitudes toward nontraditional venues, and acceptability of test results delivery options. A total of 80 ethnographic one-on-one telephone interviews were conducted with African American, Caucasian, and Latina women, aged 15 to 25 years, in 10 metropolitan areas of the United States. Interviews were recorded, transcribed, and analyzed using NVivo2. Alternative STD-testing venues and results delivery channels are valued by young women for their convenience and accessibility, but they must also offer privacy, confidentiality, and emotional/informational support to be acceptable. Assuring provider (or self) competence and valid/accurate test results is also important. Although new technologies have been embraced by young women for personal and social uses, they may not be as readily embraced for the provision of STD-related services. Additional social marketing efforts may be needed to promote acceptance of nontraditional STD-testing settings and results delivery methods.

  9. An ultra-high field strength MR image-guided robotic needle delivery system for in-bore small animal interventions.

    PubMed

    Gravett, Matthew; Cepek, Jeremy; Fenster, Aaron

    2017-11-01

    The purpose of this study was to develop and validate an image-guided robotic needle delivery system for accurate and repeatable needle targeting procedures in mouse brains inside the 12 cm inner diameter gradient coil insert of a 9.4 T MR scanner. Many preclinical research techniques require the use of accurate needle deliveries to soft tissues, including brain tissue. Soft tissues are optimally visualized in MR images, which offer high-soft tissue contrast, as well as a range of unique imaging techniques, including functional, spectroscopy and thermal imaging, however, there are currently no solutions for delivering needles to small animal brains inside the bore of an ultra-high field MR scanner. This paper describes the mechatronic design, evaluation of MR compatibility, registration technique, mechanical calibration, the quantitative validation of the in-bore image-guided needle targeting accuracy and repeatability, and demonstrated the system's ability to deliver needles in situ. Our six degree-of-freedom, MR compatible, mechatronic system was designed to fit inside the bore of a 9.4 T MR scanner and is actuated using a combination of piezoelectric and hydraulic mechanisms. The MR compatibility and targeting accuracy of the needle delivery system are evaluated to ensure that the system is precisely calibrated to perform the needle targeting procedures. A semi-automated image registration is performed to link the robot coordinates to the MR coordinate system. Soft tissue targets can be accurately localized in MR images, followed by automatic alignment of the needle trajectory to the target. Intra-procedure visualization of the needle target location and the needle were confirmed through MR images after needle insertion. The effects of geometric distortions and signal noise were found to be below threshold that would have an impact on the accuracy of the system. The system was found to have negligible effect on the MR image signal noise and geometric distortion

  10. Peptides for Specific Intracellular Delivery and Targeting of Nanoparticles: Implications for Developing Nanoparticle-Mediated Drug Delivery

    DTIC Science & Technology

    2010-01-01

    for selective delivery of therapeutics and imaging agents to the tumour vasculature. Drug Resist. Update 8(6), 381–402 (2005). 89 Smith BR, Cheng Z...component can be realized. Select examples from the literature have already demonstrated the feasibility of generating hybrid NP–peptide constructs in...peptide-mediated delivery of NP-based imaging agents (fluorescence and magnetic resonance), drug-delivery vehicles, therapeutic proteins and nucleic

  11. Microneedle-mediated transdermal bacteriophage delivery

    PubMed Central

    Ryan, Elizabeth; Garland, Martin J.; Singh, Thakur Raghu Raj; Bambury, Eoin; O’Dea, John; Migalska, Katarzyna; Gorman, Sean P.; McCarthy, Helen O.; Gilmore, Brendan F.; Donnelly, Ryan F.

    2012-01-01

    Interest in bacteriophages as therapeutic agents has recently been reawakened. Parenteral delivery is the most routinely-employed method of administration. However, injection of phages has numerous disadvantages, such as the requirement of a health professional for administration and the possibility of cross-contamination. Transdermal delivery offers one potential means of overcoming many of these problems. The present study utilized a novel poly (carbonate) (PC) hollow microneedle (MN) device for the transdermal delivery of Escherichia coli-specific T4 bacteriophages both in vitro and in vivo. MN successfully achieved bacteriophage delivery in vitro across dermatomed and full thickness skin. A concentration of 2.67 × 106 PFU/ml (plaque forming units per ml) was detected in the receiver compartment when delivered across dermatomed skin and 4.0 × 103 PFU/ml was detected in the receiver compartment when delivered across full thickness skin. An in vivo study resulted in 4.13 × 103 PFU/ml being detected in blood 30 min following initial MN-mediated phage administration. Clearance occurred rapidly, with phages being completely cleared from the systemic circulation within 24 h, which was expected in the absence of infection. We have shown here that MN-mediated delivery allows successful systemic phage absorption. Accordingly, bacteriophage-based therapeutics may now have an alternative route for systemic delivery. Once fully-investigated, this could lead to more widespread investigation of these interesting therapeutic viruses. PMID:22750416

  12. Application of time-resolved fluorescence for direct and continuous probing of release from polymeric delivery vehicles.

    PubMed

    Viger, Mathieu L; Sheng, Wangzhong; McFearin, Cathryn L; Berezin, Mikhail Y; Almutairi, Adah

    2013-11-10

    Though accurately evaluating the kinetics of release is critical for validating newly designed therapeutic carriers for in vivo applications, few methods yet exist for release measurement in real time and without the need for any sample preparation. Many of the current approaches (e.g. chromatographic methods, absorption spectroscopy, or NMR spectroscopy) rely on isolation of the released material from the loaded vehicles, which require additional sample purification and can lead to loss of accuracy when probing fast kinetics of release. In this study we describe the use of time-resolved fluorescence for in situ monitoring of small molecule release kinetics from biodegradable polymeric drug delivery systems. This method relies on the observation that fluorescent reporters being released from polymeric drug delivery systems possess distinct excited-state lifetime components, reflecting their different environments in the particle suspensions, i.e., confined in the polymer matrices or free in the aqueous environment. These distinct lifetimes enable real-time quantitative mapping of the relative concentrations of dye in each population to obtain precise and accurate temporal information on the release profile of particular carrier/payload combinations. We found that fluorescence lifetime better distinguishes subtle differences in release profiles (e.g. differences associated with dye loading) than conventional steady-state fluorescence measurements, which represent the averaged dye behavior over the entire scan. Given the method's applicability to both hydrophobic and hydrophilic cargo, it could be employed to model the release of any drug-carrier combination. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. The delivery of therapeutic oligonucleotides

    PubMed Central

    Juliano, Rudolph L.

    2016-01-01

    The oligonucleotide therapeutics field has seen remarkable progress over the last few years with the approval of the first antisense drug and with promising developments in late stage clinical trials using siRNA or splice switching oligonucleotides. However, effective delivery of oligonucleotides to their intracellular sites of action remains a major issue. This review will describe the biological basis of oligonucleotide delivery including the nature of various tissue barriers and the mechanisms of cellular uptake and intracellular trafficking of oligonucleotides. It will then examine a variety of current approaches for enhancing the delivery of oligonucleotides. This includes molecular scale targeted ligand-oligonucleotide conjugates, lipid- and polymer-based nanoparticles, antibody conjugates and small molecules that improve oligonucleotide delivery. The merits and liabilities of these approaches will be discussed in the context of the underlying basic biology. PMID:27084936

  14. 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

  15. Poster – 13: Evaluation of an in-house CCD camera film dosimetry imaging system for small field deliveries

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

    Lalonde, Michel; Alexander, Kevin; Olding, Tim

    Purpose: Radiochromic film dosimetry is a standard technique used in clinics to verify modern conformal radiation therapy delivery, and sometimes in research to validate other dosimeters. We are using film as a standard for comparison as we improve high-resolution three-dimensional gel systems for small field dosimetry; however, precise film dosimetry can be technically challenging. We report here measurements for fractionated stereotactic radiation therapy (FSRT) delivered using volumetric modulated arc therapy (VMAT) to investigate the accuracy and reproducibility of film measurements with a novel in-house readout system. We show that radiochromic film can accurately and reproducibly validate FSRT deliveries and alsomore » benchmark our gel dosimetry work. Methods: VMAT FSRT plans for metastases alone (PTV{sub MET}) and whole brain plus metastases (WB+PTV{sub MET}) were delivered onto a multi-configurational phantom with a sheet of EBT3 Gafchromic film inserted mid-plane. A dose of 400 cGy was prescribed to 4 small PTV{sub MET} structures in the phantom, while a WB structure was prescribed a dose of 200 cGy in the WB+PTV{sub MET} iterations. Doses generated from film readout with our in-house system were compared to treatment planned doses. Each delivery was repeated multiple times to assess reproducibility. Results and Conclusions: The reproducibility of film optical density readout was excellent throughout all experiments. Doses measured from the film agreed well with plans for the WB+PTV{sub MET} delivery. But, film doses for PTV{sub MET} only deliveries were significantly below planned doses. This discrepancy is due to stray/scattered light perturbations in our system during readout. Corrections schemes will be presented.« less

  16. Space age health care delivery

    NASA Technical Reports Server (NTRS)

    Jones, W. L.

    1977-01-01

    Space age health care delivery is being delivered to both NASA astronauts and employees with primary emphasis on preventive medicine. The program relies heavily on comprehensive health physical exams, health education, screening programs and physical fitness programs. Medical data from the program is stored in a computer bank so epidemiological significance can be established and better procedures can be obtained. Besides health care delivery to the NASA population, NASA is working with HEW on a telemedicine project STARPAHC, applying space technology to provide health care delivery to remotely located populations.

  17. Vaginal delivery of breech presentation.

    PubMed

    Kotaska, Andrew; Menticoglou, Savas; Gagnon, Robert

    2009-06-01

    To review the physiology of breech birth; to discern the risks and benefits of a trial of labour versus planned Caesarean section; and to recommend to obstetricians, family physicians, midwives, obstetrical nurses, anaesthesiologists, pediatricians, and other health care providers selection criteria, intrapartum management parameters, and delivery techniques for a trial of vaginal breech birth. Trial of labour in an appropriate setting or delivery by pre-emptive Caesarean section for women with a singleton breech fetus at term. Reduced perinatal mortality, short-term neonatal morbidity, long-term infant morbidity, and short- and long-term maternal morbidity and mortality. Medline was searched for randomized trials, prospective cohort studies, and selected retrospective cohort studies comparing planned Caesarean section with a planned trial of labour; selected epidemiological studies comparing delivery by Caesarean section with vaginal breech delivery; and studies comparing long-term outcomes in breech infants born vaginally or by Caesarean section. Additional articles were identified through bibliography tracing up to June 1, 2008. The evidence collected was reviewed by the Maternal Fetal Medicine Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) and quantified using the criteria and classifications of the Canadian Task Force on Preventive Health Care. This guideline was compared with the 2006 American College of Obstetrician's Committee Opinion on the mode of term singleton breech delivery and with the 2006 Royal College of Obstetrician and Gynaecologists Green Top Guideline: The Management of Breech Presentation. The document was reviewed by Canadian and International clinicians with particular expertise in breech vaginal delivery. The Society of Obstetricians and Gynaecologists of Canada. SUMMARY STATEMENTS: 1. Vaginal breech birth can be associated with a higher risk of perinatal mortality and short-term neonatal morbidity than

  18. 29 CFR 780.154 - Delivery “to market.”

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Delivery âto market.â 780.154 Section 780.154 Labor... of Agriculture Specified Delivery Operations § 780.154 Delivery “to market.” The term “delivery... processor to which the farmer delivers his products. Delivery to market ends with the delivery of the...

  19. 29 CFR 780.154 - Delivery “to market.”

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 3 2011-07-01 2011-07-01 false Delivery âto market.â 780.154 Section 780.154 Labor... of Agriculture Specified Delivery Operations § 780.154 Delivery “to market.” The term “delivery... processor to which the farmer delivers his products. Delivery to market ends with the delivery of the...

  20. MicroRNA delivery for regenerative medicine.

    PubMed

    Peng, Bo; Chen, Yongming; Leong, Kam W

    2015-07-01

    MicroRNA (miRNA) directs post-transcriptional regulation of a network of genes by targeting mRNA. Although relatively recent in development, many miRNAs direct differentiation of various stem cells including induced pluripotent stem cells (iPSCs), a major player in regenerative medicine. An effective and safe delivery of miRNA holds the key to translating miRNA technologies. Both viral and nonviral delivery systems have seen success in miRNA delivery, and each approach possesses advantages and disadvantages. A number of studies have demonstrated success in augmenting osteogenesis, improving cardiogenesis, and reducing fibrosis among many other tissue engineering applications. A scaffold-based approach with the possibility of local and sustained delivery of miRNA is particularly attractive since the physical cues provided by the scaffold may synergize with the biochemical cues induced by miRNA therapy. Herein, we first briefly cover the application of miRNA to direct stem cell fate via replacement and inhibition therapies, followed by the discussion of the promising viral and nonviral delivery systems. Next we present the unique advantages of a scaffold-based delivery in achieving lineage-specific differentiation and tissue development. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Drug Delivery in Cancer Therapy, Quo Vadis?

    PubMed

    Lu, Zheng-Rong; Qiao, Peter

    2018-03-22

    The treatment of malignancies has undergone dramatic changes in the past few decades. Advances in drug delivery techniques and nanotechnology have allowed for new formulations of old drugs, so as to improve the pharmacokinetics, to enhance accumulation in solid tumors, and to reduce the significant toxic effects of these important therapeutic agents. Here, we review the published clinical data in cancer therapy of several major drug delivery systems, including targeted radionuclide therapy, antibody-drug conjugates, liposomes, polymer-drug conjugates, polymer implants, micelles, and nanoparticles. The clinical outcomes of these delivery systems from various phases of clinical trials are summarized. The success and limitations of the drug delivery strategies are discussed based on the clinical observations. In addition, the challenges in applying drug delivery for efficacious cancer therapy, including physical barriers, tumor heterogeneity, drug resistance, and metastasis, are discussed along with future perspectives of drug delivery in cancer therapy. In doing so, we intend to underscore that efficient delivery of cancer therapeutics to solid malignancies remains a major challenge in cancer therapy, and requires a multidisciplinary approach that integrates knowledge from the diverse fields of chemistry, biology, engineering, and medicine. The overall objective of this review is to improve our understanding of the clinical fate of commonly investigated drug delivery strategies, and to identify the limitations that must be addressed in future drug delivery strategies, toward the pursuit of curative therapies for cancer.

  2. Hypoxia Responsive Drug Delivery Systems in Tumor Therapy.

    PubMed

    Alimoradi, Houman; Matikonda, Siddharth S; Gamble, Allan B; Giles, Gregory I; Greish, Khaled

    2016-01-01

    Hypoxia is a common characteristic of solid tumors. It is mainly determined by low levels of oxygen resulting from imperfect vascular networks supplying most tumors. In an attempt to improve the present chemotherapeutic treatment and reduce associated side effects, several prodrug strategies have been introduced to achieve hypoxia-specific delivery of cytotoxic anticancer agents. With the advances in nanotechnology, novel delivery systems activated by the consequent outcomes of hypoxia have been developed. However, developing hypoxia responsive drug delivery systems (which only depend on low oxygen levels) is currently naïve. This review discusses four main hypoxia responsive delivery systems: polymeric based drug delivery systems, oxygen delivery systems combined with radiotherapy and chemotherapy, anaerobic bacteria which are used for delivery of genes to express anticancer proteins such as tumor necrosis alpha (TNF-α) and hypoxia-inducible transcription factors 1 alpha (HIF1α) responsive gene delivery systems.

  3. Variable delivery, fixed displacement pump

    DOEpatents

    Sommars, Mark F.

    2001-01-01

    A variable delivery, fixed displacement pump comprises a plurality of pistons reciprocated within corresponding cylinders in a cylinder block. The pistons are reciprocated by rotation of a fixed angle swash plate connected to the pistons. The pistons and cylinders cooperate to define a plurality of fluid compression chambers each have a delivery outlet. A vent port is provided from each fluid compression chamber to vent fluid therefrom during at least a portion of the reciprocal stroke of the piston. Each piston and cylinder combination cooperates to close the associated vent port during another portion of the reciprocal stroke so that fluid is then pumped through the associated delivery outlet. The delivery rate of the pump is varied by adjusting the axial position of the swash plate relative to the cylinder block, which varies the duration of the piston stroke during which the vent port is closed.

  4. Nonexposure Accurate Location K-Anonymity Algorithm in LBS

    PubMed Central

    2014-01-01

    This paper tackles location privacy protection in current location-based services (LBS) where mobile users have to report their exact location information to an LBS provider in order to obtain their desired services. Location cloaking has been proposed and well studied to protect user privacy. It blurs the user's accurate coordinate and replaces it with a well-shaped cloaked region. However, to obtain such an anonymous spatial region (ASR), nearly all existent cloaking algorithms require knowing the accurate locations of all users. Therefore, location cloaking without exposing the user's accurate location to any party is urgently needed. In this paper, we present such two nonexposure accurate location cloaking algorithms. They are designed for K-anonymity, and cloaking is performed based on the identifications (IDs) of the grid areas which were reported by all the users, instead of directly on their accurate coordinates. Experimental results show that our algorithms are more secure than the existent cloaking algorithms, need not have all the users reporting their locations all the time, and can generate smaller ASR. PMID:24605060

  5. Vial usage, device dead space, vaccine wastage, and dose accuracy of intradermal delivery devices for inactivated poliovirus vaccine (IPV).

    PubMed

    Jarrahian, Courtney; Rein-Weston, Annie; Saxon, Gene; Creelman, Ben; Kachmarik, Greg; Anand, Abhijeet; Zehrung, Darin

    2017-03-27

    Intradermal delivery of a fractional dose of inactivated poliovirus vaccine (IPV) offers potential benefits compared to intramuscular (IM) delivery, including possible cost reductions and easing of IPV supply shortages. Objectives of this study were to assess intradermal delivery devices for dead space, wastage generated by the filling process, dose accuracy, and total number of doses that can be delivered per vial. Devices tested included syringes with staked (fixed) needles (autodisable syringes and syringes used with intradermal adapters), a luer-slip needle and syringe, a mini-needle syringe, a hollow microneedle device, and disposable-syringe jet injectors with their associated filling adapters. Each device was used to withdraw 0.1-mL fractional doses from single-dose IM glass vials which were then ejected into a beaker. Both vial and device were weighed before and after filling and again after expulsion of liquid to record change in volume at each stage of the process. Data were used to calculate the number of doses that could potentially be obtained from multidose vials. Results show wide variability in dead space, dose accuracy, overall wastage, and total number of doses that can be obtained per vial among intradermal delivery devices. Syringes with staked needles had relatively low dead space and low overall wastage, and could achieve a greater number of doses per vial compared to syringes with a detachable luer-slip needle. Of the disposable-syringe jet injectors tested, one was comparable to syringes with staked needles. If intradermal delivery of IPV is introduced, selection of an intradermal delivery device can have a substantial impact on vaccine wasted during administration, and thus on the required quantity of vaccine that needs to be purchased. An ideal intradermal delivery device should be not only safe, reliable, accurate, and acceptable to users and vaccine recipients, but should also have low dead space, high dose accuracy, and low overall

  6. Presentation to delivery interval in women with early preterm delivery presenting with preterm labor: the effect of gestational age.

    PubMed

    Ashwal, Eran; Shinar, Shiri; Wertheimer, Avital; Reina, Luciena; Miremberg, Hadas; Aviram, Amir; Yogev, Yariv; Hiersch, Liran

    2017-10-01

    To evaluate the association between gestational age at presentation and interval to delivery in women with early spontaneous preterm delivery (PTD). A retrospective cohort study of women who presented with threatened preterm labor (tPTL) and intact membranes and had a spontaneous PTD <34 weeks in a university-affiliated hospital (2009-2015). The interval from presentation to delivery was compared between different gestational age subgroups. Of 67 550 deliveries during the study period, 252 met inclusion criteria. This cohort was divided to three gestational age subgroups at presentation: 24-28 6/7 weeks (n = 83), 29-31 6/7 weeks (n = 61) and 32-33 6/7 weeks (n = 108). Median time from presentation to delivery was 24.5 h. An inverse relation was observed between gestational age at presentation and admission-delivery interval (group A: 74.7 h, group B: 21.0 h, group C: 14.0 h, p < 0.001). Gestational age at presentation is inversely related to admission-delivery interval in women with tPTL and intact membranes.

  7. Telerobotic system concept for real-time soft-tissue imaging during radiotherapy beam delivery.

    PubMed

    Schlosser, Jeffrey; Salisbury, Kenneth; Hristov, Dimitre

    2010-12-01

    The curative potential of external beam radiation therapy is critically dependent on having the ability to accurately aim radiation beams at intended targets while avoiding surrounding healthy tissues. However, existing technologies are incapable of real-time, volumetric, soft-tissue imaging during radiation beam delivery, when accurate target tracking is most critical. The authors address this challenge in the development and evaluation of a novel, minimally interfering, telerobotic ultrasound (U.S.) imaging system that can be integrated with existing medical linear accelerators (LINACs) for therapy guidance. A customized human-safe robotic manipulator was designed and built to control the pressure and pitch of an abdominal U.S. transducer while avoiding LINAC gantry collisions. A haptic device was integrated to remotely control the robotic manipulator motion and U.S. image acquisition outside the LINAC room. The ability of the system to continuously maintain high quality prostate images was evaluated in volunteers over extended time periods. Treatment feasibility was assessed by comparing a clinically deployed prostate treatment plan to an alternative plan in which beam directions were restricted to sectors that did not interfere with the transabdominal U.S. transducer. To demonstrate imaging capability concurrent with delivery, robot performance and U.S. target tracking in a phantom were tested with a 15 MV radiation beam active. Remote image acquisition and maintenance of image quality with the haptic interface was successfully demonstrated over 10 min periods in representative treatment setups of volunteers. Furthermore, the robot's ability to maintain a constant probe force and desired pitch angle was unaffected by the LINAC beam. For a representative prostate patient, the dose-volume histogram (DVH) for a plan with restricted sectors remained virtually identical to the DVH of a clinically deployed plan. With reduced margins, as would be enabled by real

  8. Microneedles As a Delivery System for Gene Therapy

    PubMed Central

    Chen, Wei; Li, Hui; Shi, De; Liu, Zhenguo; Yuan, Weien

    2016-01-01

    Gene delivery systems can be divided to two major types: vector-based (either viral vector or non-viral vector) and physical delivery technologies. Many physical carriers, such as electroporation, gene gun, ultrasound start to be proved to have the potential to enable gene therapy. A relatively new physical delivery technology for gene delivery consists of microneedles (MNs), which has been studied in many fields and for many molecule types and indications. Microneedles can penetrate the stratum corneum, which is the main barrier for drug delivery through the skin with ease of administration and without significant pain. Many different kinds of MNs, such as metal MNs, coated MNs, dissolving MNs have turned out to be promising in gene delivery. In this review, we discussed the potential as well as the challenges of utilizing MNs to deliver nucleic acids for gene therapy. We also proposed that a combination of MNs and other gene delivery approaches may lead to a better delivery system for gene therapy. PMID:27303298

  9. 77 FR 3800 - Accurate NDE & Inspection, LLC; Confirmatory Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-25

    ... In the Matter of Accurate NDE & Docket: 150-00017, General Inspection, LLC Broussard, Louisiana... an attempt to resolve issues associated with this matter. In response, on August 9, 2011, Accurate NDE requested ADR to resolve this matter with the NRC. On September 28, 2011, the NRC and Accurate NDE...

  10. Filled Prescriptions for Opioids After Vaginal Delivery.

    PubMed

    Jarlenski, Marian; Bodnar, Lisa M; Kim, Joo Yeon; Donohue, Julie; Krans, Elizabeth E; Bogen, Debra L

    2017-03-01

    To estimate the prevalence of filled opioid prescriptions after vaginal delivery. We conducted a retrospective cohort study of 164,720 Medicaid-enrolled women in Pennsylvania who delivered a liveborn neonate vaginally from 2008 to 2013, excluding women who used opioids during pregnancy or who had an opioid use disorder. We assessed overall filled prescriptions as well as filled prescriptions in the presence or absence of the following pain-inducing conditions: bilateral tubal ligation, perineal laceration, or episiotomy. Outcomes included a binary measure of whether a woman had any opioid prescription fill 5 days or less after delivery and, among those women, a second opioid prescription fill 6-60 days after delivery. Among women with no coded pain-inducing conditions at delivery, we used multivariable logistic regression with standard errors clustered to account for within-hospital correlation to assess the association between patient characteristics and odds of a filled opioid prescription. Twelve percent of women (n=18,131) filled an outpatient opioid prescription 5 days or less after vaginal delivery; among those women, 14% (n=2,592, or 1.6% of the total) filled a second opioid prescription 6-60 days after delivery. Of the former, 5,110 (28.2%) had one or more pain-inducing conditions. Predictors of filled opioid prescriptions with no observed pain-inducing condition at delivery included tobacco use (adjusted odds ratio [OR] 1.3, 95% confidence interval [CI] 1.2-1.4) and a mental health condition (adjusted OR 1.3, 95% CI 1.2-1.4). Having a diagnosis of substance use disorder other than opioid use disorder was not associated with filling an opioid prescription 5 days or less after delivery, but was associated with having a second opioid prescription 6-60 days after delivery (adjusted OR 1.4, 95% CI 1.2-1.6). More than 1 in 10 Medicaid-enrolled women fill an outpatient opioid prescription after vaginal delivery. National opioid-prescribing recommendations for

  11. Convection-Enhanced Delivery for Diffuse Intrinsic Pontine Glioma Treatment.

    PubMed

    Zhou, Zhiping; Singh, Ranjodh; Souweidane, Mark M

    2017-01-01

    Convection-enhanced delivery (CED) is a technique designed to deliver drugs directly into the brain or tumors. Its ability to bypass the blood-brain barrier (BBB), one of the major hurdles in delivering drugs to the brain, has made it a promising drug delivery method for the treatment of primary brain tumors. A number of clinical trials utilizing CED of various therapeutic agents have been conducted to treat patients with supratentorial high-grade gliomas. Significant responses have been observed in certain patients in all of these trials. However, the insufficient ability to monitor drug distribution and pharmacokinetics hampers CED from achieving its potentials on a larger scale. Brainstem CED for diffuse intrinsic pontine glioma (DIPG) treatment is appealing because this tumor is compact and has no definitive treatment. The safety of brainstem CED has been established in small and large animals, and recently in early stage clinical trials. There are a few current clinical trials of brainstem CED in treating DIPG patients using targeted macromolecules such as antibodies and immunotoxins. Future advances for CED in DIPG treatment will come from several directions including: choosing the right agents for infusion; developing better agents and regimen for DIPG infusion; improving instruments and technique for easier and accurate surgical targeting and for allowing multisession or prolonged infusion to implement optimal time sequence; and better understanding and control of drug distribution, clearance and time sequence. CED-based therapies for DIPG will continue to evolve with new understanding of the technique and the disease.

  12. Convection-Enhanced Delivery for Diffuse Intrinsic Pontine Glioma Treatment

    PubMed Central

    Zhou, Zhiping; Singh, Ranjodh; Souweidane, Mark M.

    2017-01-01

    Convection-enhanced delivery (CED) is a technique designed to deliver drugs directly into the brain or tumors. Its ability to bypass the blood-brain barrier (BBB), one of the major hurdles in delivering drugs to the brain, has made it a promising drug delivery method for the treatment of primary brain tumors. A number of clinical trials utilizing CED of various therapeutic agents have been conducted to treat patients with supratentorial high-grade gliomas. Significant responses have been observed in certain patients in all of these trials. However, the insufficient ability to monitor drug distribution and pharmacokinetics hampers CED from achieving its potentials on a larger scale. Brainstem CED for diffuse intrinsic pontine glioma (DIPG) treatment is appealing because this tumor is compact and has no definitive treatment. The safety of brainstem CED has been established in small and large animals, and recently in early stage clinical trials. There are a few current clinical trials of brainstem CED in treating DIPG patients using targeted macromolecules such as antibodies and immunotoxins. Future advances for CED in DIPG treatment will come from several directions including: choosing the right agents for infusion; developing better agents and regimen for DIPG infusion; improving instruments and technique for easier and accurate surgical targeting and for allowing multisession or prolonged infusion to implement optimal time sequence; and better understanding and control of drug distribution, clearance and time sequence. CED-based therapies for DIPG will continue to evolve with new understanding of the technique and the disease. PMID:27306036

  13. Protein-Based Drug-Delivery Materials

    PubMed Central

    Jao, Dave; Xue, Ye; Medina, Jethro; Hu, Xiao

    2017-01-01

    There is a pressing need for long-term, controlled drug release for sustained treatment of chronic or persistent medical conditions and diseases. Guided drug delivery is difficult because therapeutic compounds need to survive numerous transport barriers and binding targets throughout the body. Nanoscale protein-based polymers are increasingly used for drug and vaccine delivery to cross these biological barriers and through blood circulation to their molecular site of action. Protein-based polymers compared to synthetic polymers have the advantages of good biocompatibility, biodegradability, environmental sustainability, cost effectiveness and availability. This review addresses the sources of protein-based polymers, compares the similarity and differences, and highlights characteristic properties and functionality of these protein materials for sustained and controlled drug release. Targeted drug delivery using highly functional multicomponent protein composites to guide active drugs to the site of interest will also be discussed. A systematical elucidation of drug-delivery efficiency in the case of molecular weight, particle size, shape, morphology, and porosity of materials will then be demonstrated to achieve increased drug absorption. Finally, several important biomedical applications of protein-based materials with drug-delivery function—including bone healing, antibiotic release, wound healing, and corneal regeneration, as well as diabetes, neuroinflammation and cancer treatments—are summarized at the end of this review. PMID:28772877

  14. Protein-Based Drug-Delivery Materials.

    PubMed

    Jao, Dave; Xue, Ye; Medina, Jethro; Hu, Xiao

    2017-05-09

    There is a pressing need for long-term, controlled drug release for sustained treatment of chronic or persistent medical conditions and diseases. Guided drug delivery is difficult because therapeutic compounds need to survive numerous transport barriers and binding targets throughout the body. Nanoscale protein-based polymers are increasingly used for drug and vaccine delivery to cross these biological barriers and through blood circulation to their molecular site of action. Protein-based polymers compared to synthetic polymers have the advantages of good biocompatibility, biodegradability, environmental sustainability, cost effectiveness and availability. This review addresses the sources of protein-based polymers, compares the similarity and differences, and highlights characteristic properties and functionality of these protein materials for sustained and controlled drug release. Targeted drug delivery using highly functional multicomponent protein composites to guide active drugs to the site of interest will also be discussed. A systematical elucidation of drug-delivery efficiency in the case of molecular weight, particle size, shape, morphology, and porosity of materials will then be demonstrated to achieve increased drug absorption. Finally, several important biomedical applications of protein-based materials with drug-delivery function-including bone healing, antibiotic release, wound healing, and corneal regeneration, as well as diabetes, neuroinflammation and cancer treatments-are summarized at the end of this review.

  15. [What type of delivery for twins?].

    PubMed

    Vendittelli, F; Accoceberry, M; Savary, D; Laurichesse-Delmas, H; Gallot, D; Jacquetin, B; Lémery, D

    2009-12-01

    To determine if perinatal and neonatal morbidity and mortality is improved by a planned caesarean section for twins before and at term. A systematic search was conducted in Medline between May 2001 and December 2008. Randomised controlled studies and meta-analysis were researched at first. There is no evidence to support a policy of planned caesarean section or vaginal delivery for twins before term or at term whatever the presentation of the first twin. There is also no evidence to support a policy of caesarean section or vaginal delivery for a patient with a history of prior caesarean section. Vaginal delivery must be made in the presence of an obstetrician, an anaesthesiologist, and a paediatrician in a level maternity adapted to the risks of the future newborn. Otherwise, there is no evidence to support a policy of planned caesarean delivery for twins but the type of delivery has to be decided with the informed patient. Copyright © 2009 Elsevier Masson SAS. All rights reserved.

  16. Convection-enhanced delivery of M13 bacteriophage to the brain

    PubMed Central

    Ksendzovsky, Alexander; Walbridge, Stuart; Saunders, Richard C.; Asthagiri, Ashok R.; Heiss, John D.; Lonser, Russell R.

    2013-01-01

    Object Recent studies indicate that M13 bacteriophage, a very large nanoparticle, binds to β-amyloid and α-synuclein proteins, leading to plaque disaggregation in models of Alzheimer and Parkinson disease. To determine the feasibility, safety, and characteristics of convection-enhanced delivery (CED) of M13 bacteriophage to the brain, the authors perfused primate brains with bacteriophage. Methods Four nonhuman primates underwent CED of M13 bacteriophage (900 nm) to thalamic gray matter (4 infusions) and frontal white matter (3 infusions). Bacteriophage was coinfused with Gd-DTPA (1 mM), and serial MRI studies were performed during infusion. Animals were monitored for neurological deficits and were killed 3 days after infusion. Tissues were analyzed for bacteriophage distribution. Results Real-time T1-weighted MRI studies of coinfused Gd-DTPA during infusion demonstrated a discrete region of perfusion in both thalamic gray and frontal white matter. An MRI-volumetric analysis revealed that the mean volume of distribution (Vd) to volume of infusion (Vi) ratio of M13 bacteriophage was 2.3 ± 0.2 in gray matter and 1.9 ± 0.3 in white matter. The mean values are expressed ± SD. Immunohistochemical analysis demonstrated mean Vd:Vi ratios of 2.9 ± 0.2 in gray matter and 2.1 ± 0.3 in white matter. The Gd-DTPA accurately tracked M13 bacteriophage distribution (the mean difference between imaging and actual bacteriophage Vd was insignificant [p > 0.05], and was −2.2% ± 9.9% in thalamic gray matter and 9.1% ± 9.5% in frontal white matter). Immunohistochemical analysis revealed evidence of additional spread from the initial delivery site in white matter (mean Vd:Vi, 16.1 ± 9.1). All animals remained neurologically intact after infusion during the observation period, and histological studies revealed no evidence of toxicity. Conclusions The CED method can be used successfully and safely to distribute M13 bacteriophage in the brain. Furthermore, additional white

  17. Convection-enhanced delivery of M13 bacteriophage to the brain.

    PubMed

    Ksendzovsky, Alexander; Walbridge, Stuart; Saunders, Richard C; Asthagiri, Ashok R; Heiss, John D; Lonser, Russell R

    2012-08-01

    Recent studies indicate that M13 bacteriophage, a very large nanoparticle, binds to β-amyloid and α-synuclein proteins, leading to plaque disaggregation in models of Alzheimer and Parkinson disease. To determine the feasibility, safety, and characteristics of convection-enhanced delivery (CED) of M13 bacteriophage to the brain, the authors perfused primate brains with bacteriophage. Four nonhuman primates underwent CED of M13 bacteriophage (900 nm) to thalamic gray matter (4 infusions) and frontal white matter (3 infusions). Bacteriophage was coinfused with Gd-DTPA (1 mM), and serial MRI studies were performed during infusion. Animals were monitored for neurological deficits and were killed 3 days after infusion. Tissues were analyzed for bacteriophage distribution. Real-time T1-weighted MRI studies of coinfused Gd-DTPA during infusion demonstrated a discrete region of perfusion in both thalamic gray and frontal white matter. An MRI-volumetric analysis revealed that the mean volume of distribution (Vd) to volume of infusion (Vi) ratio of M13 bacteriophage was 2.3 ± 0.2 in gray matter and 1.9 ± 0.3 in white matter. The mean values are expressed ± SD. Immunohistochemical analysis demonstrated mean Vd:Vi ratios of 2.9 ± 0.2 in gray matter and 2.1 ± 0.3 in white matter. The Gd-DTPA accurately tracked M13 bacteriophage distribution (the mean difference between imaging and actual bacteriophage Vd was insignificant [p > 0.05], and was -2.2% ± 9.9% in thalamic gray matter and 9.1% ± 9.5% in frontal white matter). Immunohistochemical analysis revealed evidence of additional spread from the initial delivery site in white matter (mean Vd:Vi, 16.1 ± 9.1). All animals remained neurologically intact after infusion during the observation period, and histological studies revealed no evidence of toxicity. The CED method can be used successfully and safely to distribute M13 bacteriophage in the brain. Furthermore, additional white matter spread after infusion cessation

  18. 49 CFR 663.39 - Post-delivery audit review.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... the contract or at law. (b) This provision does not preclude the recipient and manufacturer from..., DEPARTMENT OF TRANSPORTATION PRE-AWARD AND POST-DELIVERY AUDITS OF ROLLING STOCK PURCHASES Post-Delivery Audits § 663.39 Post-delivery audit review. (a) If a recipient cannot complete a post-delivery audit...

  19. 49 CFR 663.39 - Post-delivery audit review.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... the contract or at law. (b) This provision does not preclude the recipient and manufacturer from..., DEPARTMENT OF TRANSPORTATION PRE-AWARD AND POST-DELIVERY AUDITS OF ROLLING STOCK PURCHASES Post-Delivery Audits § 663.39 Post-delivery audit review. (a) If a recipient cannot complete a post-delivery audit...

  20. Antibiotic prophylaxis for operative vaginal delivery.

    PubMed

    Liabsuetrakul, Tippawan; Choobun, Thanapan; Peeyananjarassri, Krantarat; Islam, Q Monir

    2017-08-05

    Vacuum and forceps assisted vaginal deliveries are reported to increase the incidence of postpartum infections and maternal readmission to hospital compared to spontaneous vaginal delivery. Prophylactic antibiotics may be prescribed to prevent these infections. However, the benefit of antibiotic prophylaxis for operative vaginal deliveries is still unclear. To assess the effectiveness and safety of antibiotic prophylaxis in reducing infectious puerperal morbidities in women undergoing operative vaginal deliveries including vacuum or forceps deliveries, or both. We searched Cochrane Pregnancy and Childbirth's Trials Register (12 July 2017), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (12 July 2017) and reference lists of retrieved studies. All randomised trials comparing any prophylactic antibiotic regimens with placebo or no treatment in women undergoing vacuum or forceps deliveries were eligible. Participants were all pregnant women without evidence of infections or other indications for antibiotics of any gestational age undergoing vacuum or forceps delivery for any indications. Interventions were any antibiotic prophylaxis (any dosage regimen, any route of administration or at any time during delivery or the puerperium) compared with either placebo or no treatment. Two review authors assessed trial eligibility and methodological quality. Two review authors extracted the data independently using prepared data extraction forms. Any discrepancies were resolved by discussion and a consensus reached through discussion with all review authors. We assessed methodological quality of the one included trial using the GRADE approach. One trial, involving 393 women undergoing either vacuum or forceps deliveries, was included. The trial compared the antibiotic intravenous cefotetan after cord clamping compared with no treatment. This trial reported only two out of the nine outcomes specified in this review. Seven women in the group

  1. Nasal-nanotechnology: revolution for efficient therapeutics delivery.

    PubMed

    Kumar, Amrish; Pandey, Aditya Nath; Jain, Sunil Kumar

    2016-01-01

    In recent years, nanotechnology-based delivery systems have gained interest to overcome the problems of restricted absorption of therapeutic agents from the nasal cavity, depending upon the physicochemical properties of the drug and physiological properties of the human nose. The well-tolerated and non-invasive nasal drug delivery when combined with the nanotechnology-based novel formulations and carriers, opens the way for the effective systemic and brain targeting delivery of various therapeutic agents. To accomplish competent drug delivery, it is imperative to recognize the interactions among the nanomaterials and the nasal biological environment, targeting cell-surface receptors, drug release, multiple drug administration, stability of therapeutic agents and molecular mechanisms of cell signaling involved in patho-biology of the disease under consideration. Quite a few systems have been successfully formulated using nanomaterials for intranasal (IN) delivery. Carbon nanotubes (CNTs), chitosan, polylactic-co-glycolic acid (PLGA) and PLGA-based nanosystems have also been studied in vitro and in vivo for the delivery of several therapeutic agents which shown promising concentrations in the brain after nasal administration. The use of nanomaterials including peptide-based nanotubes and nanogels (NGs) for vaccine delivery via nasal route is a new approach to control the disease progression. In this review, the recent developments in nanotechnology utilized for nasal drug delivery have been discussed.

  2. A Systems Approach to Nitrogen Delivery

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

    Goins, Bobby

    A systems based approach will be used to evaluate the nitrogen delivery process. This approach involves principles found in Lean, Reliability, Systems Thinking, and Requirements. This unique combination of principles and thought process yields a very in depth look into the system to which it is applied. By applying a systems based approach to the nitrogen delivery process there should be improvements in cycle time, efficiency, and a reduction in the required number of personnel needed to sustain the delivery process. This will in turn reduce the amount of demurrage charges that the site incurs. In addition there should bemore » less frustration associated with the delivery process.« less

  3. Drug Delivery to CNS: Challenges and Opportunities with Emphasis on Biomaterials Based Drug Delivery Strategies.

    PubMed

    Khambhla, Ekta; Shah, Viral; Baviskar, Kalpesh

    2016-01-01

    The current epoch has witnessed a lifestyle impregnated with stress, which is a major cause of several neurological disorders. High morbidity and mortality rate due to neurological diseases and disorders have generated a huge social impact. Despite voluminous research, patients suffering from fatal and/or debilitating CNS diseases such as brain tumors, HIV, encephalopathy, Alzheimer's, epilepsy, Parkinson's, migraine and multiple sclerosis outnumbered those suffering from systemic cancer or heart diseases. The brain being a highly sensitive neuronal organ, has evolved with vasculature barriers, which regulates the efflux and influx of substances to CNS. Treatment of CNS diseases/disorders is challenging because of physiologic, metabolic and biochemical obstacles created by these barriers which comprise mainly of BBB and BCFB. The inability of achieving therapeutically active concentration has become the bottleneck level difficulty, hampering the therapeutic efficiency of several promising drug candidates for CNS related disorders. Parallel maturation of an effective CNS drug delivery strategy with CNS drug discovery is the need of the hour. Recently, the focus of the pharmaceutical community has aggravated in the direction of developing novel and more efficient drug delivery systems, giving the potential of more effective and safer CNS therapies. The present review outlines several hurdles in drug delivery to the CNS along with ideal physicochemical properties desired in drug substance/formulation for CNS delivery. The review also focuses on different conventional and novel strategies for drug delivery to the CNS. The article also assesses and emphasizes on possible benefits of biomaterial based formulations for drug delivery to the CNS.

  4. Issues in Commercial Document Delivery.

    ERIC Educational Resources Information Center

    Marcinko, Randall Wayne

    1997-01-01

    Discusses (1) the history of document delivery; (2) the delivery process--end-user request, intermediary request, vendor reference, citation verification, obtaining document and source relations, quality control, transferring document to client, customer service and status, invoicing and billing, research and development, and copyright; and (3)…

  5. 49 CFR 663.39 - Post-delivery audit review.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 7 2010-10-01 2010-10-01 false Post-delivery audit review. 663.39 Section 663.39 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PRE-AWARD AND POST-DELIVERY AUDITS OF ROLLING STOCK PURCHASES Post-Delivery Audits § 663.39 Post-delivery audit...

  6. 49 CFR 663.31 - Post-delivery audit requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 7 2010-10-01 2010-10-01 false Post-delivery audit requirements. 663.31 Section 663.31 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PRE-AWARD AND POST-DELIVERY AUDITS OF ROLLING STOCK PURCHASES Post-Delivery Audits § 663.31 Post-delivery audi...

  7. Future therapeutic directions; new medications and insulin delivery in a changing world for effective diabetes management.

    PubMed

    Modi, Pankaj

    2009-09-01

    Insulin remains a key to the management of diabetes. The early addition of insulin to oral therapy in type-2 patients is recognized as an effective option that can help improve glycemic control and reduces the complications and contribute to more favorable outcomes. Controlling blood glucose levels within acceptable limits is crucial to the long-term health of patients with diabetes. The benefits of patient education and chronic disease management tools cannot be underestimated as many patients will require education and help in initiation of insulin therapy to achieve glycemic targets. The wide choice of insulin formulations and the ever-expanding range of delivery methods are now available. These methods made insulin administration easier, less painful, more discreet, and more accurate than ever before thus providing important tools to overcome barriers to insulin initiation and improve achievement of glycemic goals. In addition, exciting developments in newer therapeutics have increased the potential for optimal glycemic control. This review discusses how these approaches can help patients manage their diabetes effectively by considering new insulin formulations and delivery devices and newer therapeutics.

  8. Planning and Implementing Augmentative Communication Service Delivery, 2: Proceedings of the National Planners Conference on Assistive Device Service Delivery.

    ERIC Educational Resources Information Center

    Coston, Caroline A., Ed.

    The document consists of 30 author contributed chapters concerned with augmentative communication service delivery. Chapter titles and authors are: "Communication Options for Persons Who Cannot Speak: Planning for Service Delivery" (David Beukelman); "Planning Service Delivery Systems" (Roland Hahn II); "Planning Ohio's…

  9. Photoacoustic microscopy imaging for microneedle drug delivery

    NASA Astrophysics Data System (ADS)

    Moothanchery, Mohesh; Seeni, Razina Z.; Xu, Chenjie; Pramanik, Manojit

    2018-02-01

    The recent development of novel transdermal drug delivery systems (TDDS) using microneedle technology allows micron-sized conduits to be formed within the outermost skin layers attracting keen interest in skin as an interface for localized and systemic delivery of therapeutics. In light of this, researchers are using microneedles as tools to deliver nanoparticle formulations to targeted sites for effective therapy. However, in such studies the use of traditional histological methods are employed for characterization and do not allow for the in vivo visualization of drug delivery mechanism. Hence, this study presents a novel imaging technology to characterize microneedle based nanoparticle delivery systems using optical resolution-photoacoustic microscopy (OR-PAM). In this study in vivo transdermal delivery of gold nanoparticles using microneedles in mice ear and the spatial distribution of the nanoparticles in the tissue was successfully illustrated. Characterization of parameters that are relevant in drug delivery studies such as penetration depth, efficiency of delivered gold nanoparticles were monitored using the system. Photoacoustic microscopy proves an ideal tool for the characterization studies of microneedle properties and the studies shows microneedles as an ideal tool for precise and controlled drug delivery.

  10. Ultrasound-enhanced drug delivery for cancer.

    PubMed

    Mo, Steven; Coussios, Constantin-C; Seymour, Len; Carlisle, Robert

    2012-12-01

    Ultrasound, which has traditionally been used as a diagnostic tool, is increasingly being used in non-invasive therapy and drug delivery. Of particular interest to this review is the rapidly accumulating evidence that ultrasound may have a key role to play both in improving the targeting and the efficacy of drug delivery for cancer. Currently available ultrasound-triggerable vehicles are first described, with particular reference to the ultrasonic mechanism that can activate release and the suitability of the size range of the vehicle used for drug delivery. Further mechanical and thermal effects of ultrasound that can enhance extravasation and drug distribution following release are then critically reviewed. Acoustic cavitation is found to play a potentially key role both in achieving targeted drug release and enhanced extravasation at modest pressure amplitudes and acoustic energies, whilst simultaneously enabling real-time monitoring of the drug delivery process. The next challenge in ultrasound-enhanced drug delivery will thus be to develop a new generation of drug-carrying nanoparticles which are of the right size range for delivery to tumours, yet still capable of achieving initiation of cavitation activity and drug release at modest acoustic pressures and energies that have no safety implications for the patient.

  11. Recent advances in ophthalmic drug delivery

    PubMed Central

    Kompella, Uday B; Kadam, Rajendra S; Lee, Vincent HL

    2011-01-01

    Topical ocular drug bioavailability is notoriously poor, in the order of 5% or less. This is a consequence of effective multiple barriers to drug entry, comprising nasolacrimal drainage, epithelial drug transport barriers and clearance from the vasculature in the conjunctiva. While sustained drug delivery to the back of the eye is now feasible with intravitreal implants such as Vitrasert™ (~6 months), Retisert™ (~3 years) and Iluvien™ (~3 years), currently there are no marketed delivery systems for long-term drug delivery to the anterior segment of the eye. The purpose of this article is to summarize the resurgence in interest to prolong and improve drug entry from topical administration. These approaches include mucoadhesives, viscous polymer vehicles, transporter-targeted prodrug design, receptor-targeted functionalized nanoparticles, iontophoresis, punctal plug and contact lens delivery systems. A few of these delivery systems might be useful in treating diseases affecting the back of the eye. Their effectiveness will be compared against intravitreal implants (upper bound of effectiveness) and trans-scleral systems (lower bound of effectiveness). Refining the animal model by incorporating the latest advances in microdialysis and imaging technology is key to expanding the knowledge central to the design, testing and evaluation of the next generation of innovative ocular drug delivery systems. PMID:21399724

  12. Nanocarriers for delivery of siRNA and co-delivery of siRNA and other therapeutic agents.

    PubMed

    Zhao, Jing; Feng, Si-Shen

    2015-07-01

    A major problem in cancer treatment is the multidrug resistance. siRNA inhibitors have great advantages to solve the problem, if the bottleneck of their delivery could be well addressed by the various nanocarriers. Moreover, co-delivery of siRNA together with the various anticancer agents in one nanocarrier may maximize their additive or synergistic effect. This review provides a comprehensive summary on the state-of-the-art of the nanocarriers, which may include prodrugs, micelles, liposomes, dendrimers, nanohydrogels, solid lipid nanoparticles, nanoparticles of biodegradable polymers and nucleic acid nanocarriers for delivery of siRNA and co-delivery of siRNA together with anticancer agents with focus on synthesis of the nanocarrier materials, design and characterization, in vitro and in vivo evaluation, and prospect and challenges of nanocarriers.

  13. Delivery presentations

    MedlinePlus

    ... Labor - delivery presentation; Occiput posterior; Occiput anterior; Brow presentation References Lanni SM, Gherman R, Gonik B. Malpresentations. In: Gabbe SG, Niebyl JR, Simpson JL, et al, eds. Obstetrics: Normal and Problem Pregnancies . 7th ed. Philadelphia, ...

  14. Evaluation of delivery options for second-stage events.

    PubMed

    Bailit, Jennifer L; Grobman, William A; Rice, Madeline Murguia; Wapner, Ronald J; Reddy, Uma M; Varner, Michael W; Thorp, John M; Caritis, Steve N; Iams, Jay D; Saade, George; Rouse, Dwight J; Tolosa, Jorge E

    2016-05-01

    Cesarean delivery in the second stage of labor is common, whereas the frequency of operative vaginal delivery has been declining. However, data comparing outcomes for attempted operative vaginal delivery vs cesarean in the second stage are scant. Previous studies that examine operative vaginal delivery have compared it to a baseline risk of complications from a spontaneous vaginal delivery and cesarean delivery. However, when a woman has a need for intervention in the second stage, spontaneous vaginal delivery is not an option she or the provider can choose. Thus, the appropriate clinical comparison is cesarean vs operative vaginal delivery. Our objective was to compare outcomes by the first attempted operative delivery (vacuum, forceps vs cesarean delivery) in patients needing second-stage assistance at a fetal station of +2 or below. We conducted secondary analysis of an observational obstetric cohort in 25 academically affiliated US hospitals over a 3-year period. A subset of ≥37 weeks, nonanomalous, vertex, singletons, with no prior vaginal delivery who reached a station of +2 or below and underwent an attempt at an operative delivery were included. Indications included for operative delivery were: failure to descend, nonreassuring fetal status, labor dystocia, or maternal exhaustion. The primary outcomes included a composite neonatal outcome (death, fracture, length of stay ≥3 days beyond mother's, low Apgar, subgaleal hemorrhage, ventilator support, hypoxic encephalopathy, brachial plexus injury, facial nerve palsy) and individual maternal outcomes (postpartum hemorrhage, third- and fourth-degree tears [severe lacerations], and postpartum infection). Outcomes were examined by the 3 attempted modes of delivery. Odds ratios (OR) were calculated for primary outcomes adjusting for confounders. Final mode of delivery was quantified. In all, 2531 women met inclusion criteria. No difference in the neonatal composite outcome was observed between groups. Vacuum

  15. Evaluation of delivery options for second stage events

    PubMed Central

    Bailit, Jennifer L.; Grobman, William A.; Rice, Madeline Murguia; Wapner, Ronald J.; Reddy, Uma M.; Varner, Michael W.; Thorp, John M.; Caritis, Steve N.; Iams, Jay D.; Saade, George; Rouse, Dwight J.; Tolosa, Jorge E.

    2015-01-01

    Background Cesarean delivery in the second stage of labor is common, whereas the frequency of operative vaginal delivery has been declining. However, data comparing outcomes for attempted operative vaginal delivery in the second stage versus cesarean in the second stage are scant. Previous studies that examine operative vaginal delivery have compared it to a baseline risk of complications from a spontaneous vaginal delivery and cesarean delivery. However, when a woman has a need for intervention in the second stage, spontaneous vaginal delivery is not an option she or the provider can choose. Thus, the appropriate clinical comparison is cesarean versus operative vaginal delivery. Objective Our objective was to compare outcomes by the first attempted operative delivery (vacuum, forceps versus cesarean delivery) in patients needing second stage assistance at a fetal station of +2 or below. Study Design Secondary analysis of an observational obstetric cohort in 25 academically-affiliated U.S. hospitals over a three-year period. A subset of ≥37 weeks, non-anomalous, vertex, singletons, with no prior vaginal delivery who reached a station of +2 or below and underwent an attempt at an operative delivery were included. Indications included for operative delivery were: failure to descend, non-reassuring fetal status, labor dystocia or maternal exhaustion. The primary outcomes included a composite neonatal outcome (death, fracture, length of stay ≥3 days beyond mother’s, low Apgar, subgaleal hemorrhage, ventilator support, hypoxic encephalopathy, brachial plexus injury, facial nerve palsy) and individual maternal outcomes (postpartum hemorrhage, third and fourth degree tears [severe lacerations], and postpartum infection). Outcomes were examined by the three attempted modes of delivery. Odds ratios were calculated for primary outcomes adjusting for confounders. Final mode of delivery was quantified. Results 2531 women met inclusion criteria. Vacuum attempt was

  16. Antibiotic prophylaxis for operative vaginal delivery.

    PubMed

    Liabsuetrakul, Tippawan; Choobun, Thanapan; Peeyananjarassri, Krantarat; Islam, Q Monir

    2014-10-13

    Vacuum and forceps assisted vaginal deliveries are reported to increase the incidence of postpartum infections and maternal readmission to hospital compared to spontaneous vaginal delivery. Prophylactic antibiotics may be prescribed to prevent these infections. However, the benefit of antibiotic prophylaxis for operative vaginal deliveries is still unclear. To assess the effectiveness and safety of antibiotic prophylaxis in reducing infectious puerperal morbidities in women undergoing operative vaginal deliveries including vacuum or forceps deliveries, or both. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2014). All randomised trials comparing any prophylactic antibiotic regimens with placebo or no treatment in women undergoing vacuum or forceps deliveries were eligible. Participants were all pregnant women without evidence of infections or other indications for antibiotics of any gestational age undergoing vacuum or forceps delivery for any indications. Interventions were any antibiotic prophylaxis (any dosage regimen, any route of administration or at any time during delivery or the puerperium) compared with either placebo or no treatment. Two review authors assessed trial eligibility and methodological quality. Two review authors extracted the data independently using prepared data extraction forms. Any discrepancies were resolved by discussion and a consensus reached through discussion with all review authors. For this update, we assessed methodological quality of the one included trial using the standard Cochrane criteria and the GRADE approach. We calculated the risk ratio (RR) and mean difference (MD) using a fixed-effect model and all the review authors interpreted and discussed the results. One trial, involving 393 women undergoing either vacuum or forceps deliveries, was included. This trial identified only two out of the nine outcomes specified in this review. It reported seven women with endomyometritis in the

  17. Antibiotic prophylaxis for operative vaginal delivery.

    PubMed

    Liabsuetrakul, T; Choobun, T; Peeyananjarassri, K; Islam, M

    2004-01-01

    Vacuum and forceps assisted vaginal deliveries are reported to increase the incidence of postpartum infections and maternal readmission to hospital compared to spontaneous vaginal delivery. Prophylactic antibiotics are prescribed to prevent these infections. However, the benefit of antibiotic prophylaxis for operative vaginal deliveries is still unclear. To assess the effectiveness and safety of antibiotic prophylaxis in reducing infectious puerperal morbidities in women undergoing operative vaginal deliveries including vacuum and/or forceps deliveries. We searched the Cochrane Pregnancy and Childbirth Group trials register (November 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2003) and MEDLINE (1966 to November 2003). All randomised trials comparing any prophylactic antibiotic regimens with placebo or no treatment in women undergoing vacuum or forceps deliveries were eligible. Participants were all pregnant women without evidence of infections or other indications for antibiotics of any gestational age undergoing vacuum or forceps delivery for any indications. Interventions were any antibiotic prophylaxis (any dosage regimen, any route of administration or at any time during delivery or the puerperium) compared with either placebo or no treatment. Four reviewers assessed trial eligibility and methodological quality. Two reviewers extracted the data independently using prepared data extraction forms. Any discrepancies were resolved by discussion and a consensus reached through discussion with all reviewers. We assessed methodological quality of the included trial using the standard Cochrane criteria and the CONSORT statement of randomised controlled trials. We calculated the relative risks using a fixed effect model and all the reviewers interpreted and discussed the results. One trial, involving 393 women undergoing either vacuum or forceps deliveries, was included. This trial identified only two out of the nine

  18. SU-E-J-17: Intra-Fractional Prostate Movement Correction During Treatment Delivery Period for Prostate Cancer Using the Intra-Fractional Orthogonal KV-MV Image Pairs

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

    Zhang, J; Azawi, S; Cho-Lim, J

    Purpose: To evaluate the intra-fractional prostate movement range during the beam delivery and implement new IGRT method to correct the prostate movement during the hypofractionated prostate treatment delivery. Methods: To evaluate the prostate internal motion range during the beam delivery, 11 conventional treatments were utilized. Two-arc RapidArc plans were used for the treatment delivery. Orthogonal KV imaging is performed in the middle of the treatment to correct intra-fractional prostate movement. However, it takes gantry-mounted on-board imaging system relative long time to finish the orthogonal KV imaging because of gantry rotation. To avoid gantry movement and accelerate the IGRT processing time,more » orthogonal KV-MV image pair is tested using the OBI daily QA Cube phantom. Results: The average prostate movement between two orthogonal KV image pairs was 0.38cm (0.20cm ∼ 0.85cm). And the interval time between them was 6.71 min (4.64min ∼ 9.22 min). 2-arc beam delivery time is within 3 minutes for conventional RapidArc treatment delivery. Hypofractionated treatment or SBRT need 4 partial arc and possible non-coplanar technology, which need much longer beam delivery time. Therefore prostate movement might be larger. New orthogonal KV-MV image pair is a new method to correct the prostate movement in the middle of the beam delivery if real time tracking method is not available. Orthogonal KV-MV image pair doesn’t need gantry rotation. Images were acquired quickly which minimized possible new prostate movement. Therefore orthogonal KV-MV image pair is feasible for IGRT. Conclusion: Hypofractionated prostate treatment with less PTV margin always needs longer beam delivery time. Therefore prostate movement correction during the treatment delivery is critical. Orthogonal KV-MV imaging pair is efficient and accurate to correct the prostate movement during treatment beam delivery. Due to limited fraction number and high dose per fraction, the MV imaging

  19. SU-F-T-666: Molecular-Targeted Gold Nanorods Enhances the RBE of Proton Therapy

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

    Khoo, A; Sahoo, N; Krishnan, S

    2016-06-15

    Purpose: In recent years, proton beam radiation therapy (PBRT) has gained significant attention in the treatment of tumors in anatomically complex locations. However, the therapeutic benefit of PBRT is limited by a relative biological effectiveness (RBE) of just 1.1. The purpose of this study is to evaluate whether this limitation can be overcome by artificially enhancing the RBE using molecular-targeted gold nanorods (GNRs). Methods: Molecular-targeting of GNRs was accomplished using Cetuximab (antibody specific to epidermal growth factor receptor that is over-expressed in tumors) conjugated GNRs (cGNRs) and their binding affinity to Head and Neck cancer cells was confirmed using darkmore » field microscopy and Transmission Electron Microscopy (TEM). The radiosensitization potential of cGNRs when irradiated with photon (6MV) and proton (100 and 160 MeV) beams was determined using clonogenic assays. The RBE at 10% surviving fraction (RBE{sub 10}) for proton therapies at central and distal locations of SOBP was calculated with respect to 6 MV photons. IgGconjugated GNRs (iGNRs) were used as controls in all experiments. Results: cGNRs demonstrated significant radiosensitization when compared to iGNRs for 6MV photons (1.14 vs 1.04), 100 MeV protons (1.19 vs 1.04), and 160 MeV protons (1.17 vs 1.04). While RBE10 for proton beams at the center of SOBP revealed similar effects for both 100 and 160 MeV (RBE{sup 10}=1.39 vs 1.38; p>0.05), enhanced radiosensitization was observed at the distal SOBP with 100 MeV beams demonstrating greater effect than 160 MeV beams (RBE{sup 10}=1.79 vs 1.6; p<0.05). Conclusion: EGFR-targeting GNRs significantly enhance the RBE of protons well above the accepted 1.1 value. The enhanced RBE observed for lower energy protons (100 MeV) and at the distal SOBP suggests that low energy components may play a role in the observed radiosensitization effect. This strategy holds promise for clinical translation and could evolve as a paradigm

  20. SU-E-J-49: Distal Edge Activity Fall Off Of Proton Therapy Beams

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

    Elmekawy, A; Ewell, L; Butuceanu, C

    2014-06-01

    Purpose: To characterize and quantify the distal edge activity fall off, created in a phantom by a proton therapy beam Method and Materials: A 30x30x10cm polymethylmethacrylate phantom was irradiated with a proton therapy beam using different ranges and beams. The irradiation volume is approximated by a right circular cylinder of diameter 7.6cm and varying lengths. After irradiation, the phantom was scanned via a Philips Gemini Big Bore™ PET-CT for isotope activation. Varian Eclipse™ treatment planning system as well as ImageJ™ were used to analyze the resulting PET and CT scans. The region of activity within the phantom was longitudinally measuredmore » as a function of PET slice number. Dose estimations were made via Monte Carlo (GATE) simulation. Results: For both the spread out Bragg peak (SOBP) and the mono-energetic pristine Bragg peak proton beams, the proximal activation rise was steep: average slope −0.735 (average intensity/slice number) ± 0.091 (standard deviation) for the pristine beams and −1.149 ± 0.117 for the SOBP beams. In contrast, the distal fall offs were dissimilar. The distal fall off in activity for the pristine beams was fit well by a linear curve: R{sup 2} (Pierson Product) was 0.9968, 0.9955 and 0.9909 for the 13.5, 17.0 and 21.0cm range beams respectively. The good fit allows for a slope comparison between the different ranges. The slope varied as a function of range from 1.021 for the 13.5cm beam to 0.8407 (average intensity/slice number) for the 21.0cm beam. This dependence can be characterized: −0.0234(average intensity/slice number/cm range). For the SOBP beams, the slopes were significantly less and were also less linear: average slope 0.2628 ± 0.0474, average R{sup 2}=0.9236. Conclusion: The distal activation fall off edge for pristine proton beams was linear and steep. The corresponding quantities for SOBP beams were shallower and less linear. Philips has provided support for this work.« less

  1. 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.…

  2. FUNCTIONAL NANOPARTICLES FOR MOLECULAR IMAGING GUIDED GENE DELIVERY

    PubMed Central

    Liu, Gang; Swierczewska, Magdalena; Lee, Seulki; Chen, Xiaoyuan

    2010-01-01

    Gene therapy has great potential to bring tremendous changes in treatment of various diseases and disorders. However, one of the impediments to successful gene therapy is the inefficient delivery of genes to target tissues and the inability to monitor delivery of genes and therapeutic responses at the targeted site. The emergence of molecular imaging strategies has been pivotal in optimizing gene therapy; since it can allow us to evaluate the effectiveness of gene delivery noninvasively and spatiotemporally. Due to the unique physiochemical properties of nanomaterials, numerous functional nanoparticles show promise in accomplishing gene delivery with the necessary feature of visualizing the delivery. In this review, recent developments of nanoparticles for molecular imaging guided gene delivery are summarized. PMID:22473061

  3. Ensemble MD simulations restrained via crystallographic data: Accurate structure leads to accurate dynamics

    PubMed Central

    Xue, Yi; Skrynnikov, Nikolai R

    2014-01-01

    Currently, the best existing molecular dynamics (MD) force fields cannot accurately reproduce the global free-energy minimum which realizes the experimental protein structure. As a result, long MD trajectories tend to drift away from the starting coordinates (e.g., crystallographic structures). To address this problem, we have devised a new simulation strategy aimed at protein crystals. An MD simulation of protein crystal is essentially an ensemble simulation involving multiple protein molecules in a crystal unit cell (or a block of unit cells). To ensure that average protein coordinates remain correct during the simulation, we introduced crystallography-based restraints into the MD protocol. Because these restraints are aimed at the ensemble-average structure, they have only minimal impact on conformational dynamics of the individual protein molecules. So long as the average structure remains reasonable, the proteins move in a native-like fashion as dictated by the original force field. To validate this approach, we have used the data from solid-state NMR spectroscopy, which is the orthogonal experimental technique uniquely sensitive to protein local dynamics. The new method has been tested on the well-established model protein, ubiquitin. The ensemble-restrained MD simulations produced lower crystallographic R factors than conventional simulations; they also led to more accurate predictions for crystallographic temperature factors, solid-state chemical shifts, and backbone order parameters. The predictions for 15N R1 relaxation rates are at least as accurate as those obtained from conventional simulations. Taken together, these results suggest that the presented trajectories may be among the most realistic protein MD simulations ever reported. In this context, the ensemble restraints based on high-resolution crystallographic data can be viewed as protein-specific empirical corrections to the standard force fields. PMID:24452989

  4. Driving delivery vehicles with ultrasound ☆

    PubMed Central

    Ferrara, Katherine W.

    2009-01-01

    Therapeutic applications of ultrasound have been considered for over 40 years, with the mild hyperthermia and associated increases in perfusion produced by ultrasound harnessed in many of the earliest treatments. More recently, new mechanisms for ultrasound-based or ultrasound-enhanced therapies have been described, and there is now great momentum and enthusiasm for the clinical translation of these techniques. This dedicated issue of Advanced Drug Delivery Reviews, entitled “Ultrasound for Drug and Gene Delivery,” addresses the mechanisms by which ultrasound can enhance local drug and gene delivery and the applications that have been demonstrated at this time. In this commentary, the identified mechanisms, delivery vehicles, applications and current bottlenecks for translation of these techniques are summarized. PMID:18479775

  5. Recent advances in oral pulsatile drug delivery.

    PubMed

    Kalantzi, Lida E; Karavas, Evangelos; Koutris, Efthimios X; Bikiaris, Dimitrios N

    2009-01-01

    Pulsatile drug delivery aims to release drugs on a programmed pattern i.e.: at appropriate time and/or at appropriate site of action. Currently, it is gaining increasing attention as it offers a more sophisticated approach to the traditional sustained drug delivery i.e: a constant amount of drug released per unit time or constant blood levels. Technically, pulsatile drug delivery systems administered via the oral route could be divided into two distinct types, the time controlled delivery systems and the site-specific delivery systems. The simplest pulsatile formulation is a two layer press coated tablet consisted of polymers with different dissolution rates. Homogenicity of the coated barrier is mandatory in order to assure the predictability of the lag time. The disadvantage of such formulation is that the rupture time cannot be always adequately manipulated as it is strongly correlated with the physicochemical properties of the polymer. Gastric retentive systems, systems where the drug is released following a programmed lag phase, chronopharmaceutical drug delivery systems matching human circadian rhythms, multiunit or multilayer systems with various combinations of immediate and sustained-release preparation, are all classified under pulsatile drug delivery systems. On the other hand, site-controlled release is usually controlled by factors such as the pH of the target site, the enzymes present in the intestinal tract and the transit time/pressure of various parts of the intestine. In this review, recent patents on pulsatile drug delivery of oral dosage forms are summarized and discussed.

  6. Intracellular delivery of proteins by nanocarriers.

    PubMed

    Ray, Moumita; Lee, Yi-Wei; Scaletti, Federica; Yu, Ruijin; Rotello, Vincent M

    2017-04-01

    Intracellular delivery of proteins is potentially a game-changing approach for therapeutics. However, for most applications, the protein needs to access the cytosol to be effective. A wide variety of strategies have been developed for protein delivery, however access of delivered protein to the cytosol without acute cytotoxicity remains a critical issue. In this review we discuss recent trends in protein delivery using nanocarriers, focusing on the ability of these strategies to deliver protein into the cytosol.

  7. Nanoparticle-mediated siRNA delivery assessed in a 3D co-culture model simulating prostate cancer bone metastasis.

    PubMed

    Fitzgerald, Kathleen A; Guo, Jianfeng; Raftery, Rosanne M; Castaño, Irene Mencía; Curtin, Caroline M; Gooding, Matt; Darcy, Raphael; O' Brien, Fergal J; O' Driscoll, Caitriona M

    2016-09-25

    siRNA has emerged as a potential therapeutic for the treatment of prostate cancer but effective delivery remains a major barrier to its clinical application. This study aimed to develop and characterise a 3D in vitro co-culture model to simulate prostate cancer bone metastasis and to assess the ability of the model to investigate nanoparticle-mediated siRNA delivery and gene knockdown. PC3 or LNCaP prostate cancer cells were co-cultured with hFOB 1.19 osteoblast cells in 2D on plastic tissue culture plates and in 3D on collagen scaffolds mimicking the bone microenvironment. To characterise the co-culture model, cell proliferation, enzyme secretion and the utility of two different gene delivery vectors to mediate siRNA uptake and gene knockdown were assessed. Cell proliferation was reduced by∼50% by day 7 in the co-culture system relative to monoculture (PC3 and LNCaP co-cultures, in 2D and 3D) and an enhanced level of MMP9 (a marker of bone metastasis) was secreted into the media (1.2-4-fold increase depending on the co-culture system). A cationic cyclodextrin gene delivery vector proved significantly less toxic in the co-culture system relative to the commercially available vector Lipofectamine 2000(®). In addition, knockdown of both the GAPDH gene (minimum 15%) and RelA subunit of the NF-κB transcription factor (minimum 20%) was achieved in 2D and 3D cell co-cultures. Results indicate that the prostate cancer-osteoblast in vitro co-culture model was more physiologically relevant vs the monoculture. This model has the potential to help improve the design and efficacy of gene delivery formulations, to more accurately predict in vivo performance and, therefore, to reduce the risk of product failure in late-stage clinical development. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Laser-induced capillary leakage for blood biomarker detection and vaccine delivery via the skin.

    PubMed

    Wu, Jeffrey H; Li, Bo; Wu, Mei X

    2016-07-01

    Circulation system is the center for coordination and communication of all organs in our body. Examination of any change in its analytes or delivery of therapeutic drugs into the system consists of important medical practice in today's medicine. Two recent studies prove that brief illumination of skin with a low powered laser, at wavelengths preferentially absorbed by hemoglobin, increases the amount of circulating biomarkers in the epidermis and upper dermis by more than 1,000-fold. When probe-coated microneedle arrays are applied into laser-treated skin, plasma blood biomarkers can be reliably, accurately, and sufficiently quantified in 15∼30 min assays, with a maximal detection in one hr in a manner independent of penetration depth or a molecular mass of the biomarker. Moreover, the laser treatment permits a high efficient delivery of radiation-attenuated malarial sporozoites (RAS) into the circulation, leading to robust immunity against malaria infections, whereas similar immunization at sham-treated skin elicits poor immune responses. Thus this technology can potentially instruct designs of small, portable devices for onsite, in mobile clinics, or at home for point-of-care diagnosis and drug/vaccine delivery via the skin. Laser-induced capillary leakage (a) to induce extravasation of circualing molecules only (b) or facilitate entry of attenuated malaria sporozoites into the capillary (c). Skin illumination with a laser preferably absorbed by hemoglobin causes dilation of the capillary beneath the skin. The extravasated molecules can be sufficiently measured in the skin or guide sporozoites to enter the vessel. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Standardizing the Delivery of 20 μL of Hapten During Patch Testing.

    PubMed

    Selvick, Annika; Stauss, Kari; Strobush, Katrina; Taylor, Lauren; Picard, Alexandra; Doll, Andrea; Reeder, Margo

    2016-01-01

    The current method for patch test tray assembly requires hand dispensing a small volume of hapten onto chambers. Because of human error, this technique produces inaccurate and inconsistent results. The recommended volume of hapten for patch testing using Finn Chambers is 20 μL. The aims of this study were to create a device that standardizes the delivery of 20 μL and to compare it with the current hand dispensing technique. A device, named the Revolution, was created using the SolidWorks program. Five nurses in our Contact Dermatitis Clinic were asked to load 10 Finn Chambers using the current technique and also using the Revolution. Assembly time, volume of petrolatum, and accuracy of placement were measured. After the 3 trials, the nurses completed a survey on the 2 methods. The amount of petrolatum dispensed using the current technique ranged from 16 to 85 μL, with an average amount of 41.39 μL. The Revolution design dispensed an average of 19.78 μL. The current hand dispensing technique does not allow for accurate and consistent dispensing of 20 μL for patch testing. In contrast, the Revolution is an accurate and consistent device that can help standardize the patch testing method.

  10. Finding the most accurate method to measure head circumference for fetal weight estimation.

    PubMed

    Schmidt, Ulrike; Temerinac, Dunja; Bildstein, Katharina; Tuschy, Benjamin; Mayer, Jade; Sütterlin, Marc; Siemer, Jörn; Kehl, Sven

    2014-07-01

    Accurate measurement of fetal head biometry is important for fetal weight estimation (FWE) and is therefore an important prognostic parameter for neonatal morbidity and mortality and a valuable tool for determining the further obstetric management. Measurement of the head circumference (HC) in particular is employed in many commonly used weight equations. The aim of the present study was to find the most accurate method to measure head circumference for fetal weight estimation. This prospective study included 481 term pregnancies. Inclusion criteria were a singleton pregnancy and ultrasound examination with complete fetal biometric parameters within 3 days of delivery, and an absence of structural or chromosomal malformations. Different methods were used for ultrasound measurement of the HC (ellipse-traced, ellipse-calculated, and circle-calculated). As a reference method, HC was also determined using a measuring tape immediately after birth. FWE was carried out with Hadlock formulas, including either HC or biparietal diameter (BPD), and differences were compared using percentage error (PE), absolute percentage error (APE), limits of agreement (LOA), and cumulative distribution. The ellipse-traced method showed the best results for FWE among all of the ultrasound methods assessed. It had the lowest median APE and the narrowest LOA. With regard to the cumulative distribution, it included the largest number of cases at a discrepancy level of ±10%. The accuracy of BPD was similar to that of the ellipse-traced method when it was used instead of HC for weight estimation. Differences between the three techniques for calculating HC were small but significant. For clinical use, the ellipse-traced method should be recommended. However, when BPD is used instead of HC for FWE, the accuracy is similar to that of the ellipse-traced method. The BPD might therefore be a good alternative to head measurements in estimating fetal weight. Copyright © 2014 Elsevier Ireland Ltd. All

  11. Tip rhinoplasty--a modified delivery approach.

    PubMed

    Xavier, Rui

    2009-06-01

    For many cases of tip surgery a delivery approach is selected. If the patient has long alar cartilages, it may be difficult to deliver the cartilages without twisting or tearing the domes. In such a patient, a modified delivery approach may be easier to perform. For the modified delivery approach a transcartilaginous incision is first made and cephalic resection of the alar cartilage is performed. Then a marginal incision is made, and the remaining alar cartilage is dissected and easily delivered. After both alar cartilages being delivered, they are compared, and, if necessary, further resection is done in order to achieve perfect symmetry or to achieve the desired size of the cartilages. The cartilages may then be grafted, sutured or modified as considered necessary. We have been using the modified delivery approach for the last five years and we have had no complications of the technique itself. Two patients operated on by using this approach are presented. We believe that, in patients with long alar cartilages and a wide nasal tip, this modification turns the delivery approach into an easier and safer approach.

  12. 1 CFR 5.7 - Delivery and mailing.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 1 General Provisions 1 2011-01-01 2011-01-01 false Delivery and mailing. 5.7 Section 5.7 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER THE FEDERAL REGISTER GENERAL § 5.7 Delivery and mailing. The Government Printing Office shall distribute the Federal Register by delivery or by deposit at...

  13. 1 CFR 5.7 - Delivery and mailing.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 1 General Provisions 1 2010-01-01 2010-01-01 false Delivery and mailing. 5.7 Section 5.7 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER THE FEDERAL REGISTER GENERAL § 5.7 Delivery and mailing. The Government Printing Office shall distribute the Federal Register by delivery or by deposit at...

  14. 1 CFR 5.7 - Delivery and mailing.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 1 General Provisions 1 2014-01-01 2012-01-01 true Delivery and mailing. 5.7 Section 5.7 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER THE FEDERAL REGISTER GENERAL § 5.7 Delivery and mailing. The Government Printing Office shall distribute the Federal Register by delivery or by deposit at...

  15. 1 CFR 5.7 - Delivery and mailing.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 1 General Provisions 1 2012-01-01 2012-01-01 false Delivery and mailing. 5.7 Section 5.7 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER THE FEDERAL REGISTER GENERAL § 5.7 Delivery and mailing. The Government Printing Office shall distribute the Federal Register by delivery or by deposit at...

  16. 1 CFR 5.7 - Delivery and mailing.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 1 General Provisions 1 2013-01-01 2012-01-01 true Delivery and mailing. 5.7 Section 5.7 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER THE FEDERAL REGISTER GENERAL § 5.7 Delivery and mailing. The Government Printing Office shall distribute the Federal Register by delivery or by deposit at...

  17. Cochlear pharmacokinetics with local inner ear drug delivery using a three-dimensional finite-element computer model.

    PubMed

    Plontke, Stefan K; Siedow, Norbert; Wegener, Raimund; Zenner, Hans-Peter; Salt, Alec N

    2007-01-01

    Cochlear fluid pharmacokinetics can be better represented by three-dimensional (3D) finite-element simulations of drug dispersal. Local drug deliveries to the round window membrane are increasingly being used to treat inner ear disorders. Crucial to the development of safe therapies is knowledge of drug distribution in the inner ear with different delivery methods. Computer simulations allow application protocols and drug delivery systems to be evaluated, and may permit animal studies to be extrapolated to the larger cochlea of the human. A finite-element 3D model of the cochlea was constructed based on geometric dimensions of the guinea pig cochlea. Drug propagation along and between compartments was described by passive diffusion. To demonstrate the potential value of the model, methylprednisolone distribution in the cochlea was calculated for two clinically relevant application protocols using pharmacokinetic parameters derived from a prior one-dimensional (1D) model. In addition, a simplified geometry was used to compare results from 3D with 1D simulations. For the simplified geometry, calculated concentration profiles with distance were in excellent agreement between the 1D and the 3D models. Different drug delivery strategies produce very different concentration time courses, peak concentrations and basal-apical concentration gradients of drug. In addition, 3D computations demonstrate the existence of substantial gradients across the scalae in the basal turn. The 3D model clearly shows the presence of drug gradients across the basal scalae of guinea pigs, demonstrating the necessity of a 3D approach to predict drug movements across and between scalae with larger cross-sectional areas, such as the human, with accuracy. This is the first model to incorporate the volume of the spiral ligament and to calculate diffusion through this structure. Further development of the 3D model will have to incorporate a more accurate geometry of the entire inner ear and

  18. Cochlear Pharmacokinetics with Local Inner Ear Drug Delivery Using a Three-Dimensional Finite-Element Computer Model

    PubMed Central

    Plontke, Stefan K.; Siedow, Norbert; Wegener, Raimund; Zenner, Hans-Peter; Salt, Alec N.

    2006-01-01

    accurate geometry of the entire inner ear and incorporate more of the specific processes that contribute to drug removal from the inner ear fluids. Appropriate computer models may assist in both drug and drug delivery system design and can thus accelerate the development of a rationale-based local drug delivery to the inner ear and its successful establishment in clinical practice. PMID:17119332

  19. Novel drug delivery systems for glaucoma

    PubMed Central

    Lavik, E; Kuehn, M H; Kwon, Y H

    2011-01-01

    Reduction of intraocular pressure (IOP) by pharmaceutical or surgical means has long been the standard treatment for glaucoma. A number of excellent drugs are available that are effective in reducing IOP. These drugs are typically applied as eye drops. However, patient adherence can be poor, thus reducing the clinical efficacy of the drugs. Several novel delivery systems designed to address the issue of adherence and to ensure consistent reduction of IOP are currently under development. These delivery systems include contact lenses-releasing glaucoma medications, injectables such as biodegradable micro- and nanoparticles, and surgically implanted systems. These new technologies are aimed at increasing clinical efficacy by offering multiple delivery options and are capable of managing IOP for several months. There is also a desire to have complementary neuroprotective approaches for those who continue to show progression, despite IOP reduction. Many potential neuroprotective agents are not suitable for traditional oral or drop formulations. Their potential is dependent on developing suitable delivery systems that can provide the drugs in a sustained, local manner to the retina and optic nerve. Drug delivery systems have the potential to improve patient adherence, reduce side effects, increase efficacy, and ultimately, preserve sight for glaucoma patients. In this review, we discuss benefits and limitations of the current systems of delivery and application, as well as those on the horizon. PMID:21475311

  20. Perinatal outcomes of singleton term breech deliveries in Basra.

    PubMed

    Alshaheen, H; Abd Al-Karim, A

    2010-01-01

    This study aimed to assess the perinatal morbidity and mortality in breech deliveries, to study the correlation of parity and birth weight with perinatal mortality by mode of delivery. Of 210 women in labour in Basra maternity and child hospital, 97 underwent vaginal breech deliveries and 113 delivered by caesarean section. Birth trauma was restricted to vaginal deliveries. The perinatal mortality was significantly higher in vaginal deliveries (8.2%) compared with caesarean deliveries (0.9%). A higher perinatal mortality was recorded among infants > 3500-4000 g birth weight in vaginal deliveries. Caesarean section reduced the perinatal mortality in both nulliparous and parous women in term breech infants.

  1. Reservoir-Based Drug Delivery Systems Utilizing Microtechnology

    PubMed Central

    Stevenson, Cynthia L.; Santini, John T.; Langer, Robert

    2012-01-01

    This review covers reservoir-based drug delivery systems that incorporate microtechnology, with an emphasis on oral, dermal, and implantable systems. Key features of each technology are highlighted such as working principles, fabrication methods, dimensional constraints, and performance criteria. Reservoir-based systems include a subset of microfabricated drug delivery systems and provide unique advantages. Reservoirs, whether external to the body or implanted, provide a well-controlled environment for a drug formulation, allowing increased drug stability and prolonged delivery times. Reservoir systems have the flexibility to accommodate various delivery schemes, including zero order, pulsatile, and on demand dosing, as opposed to a standard sustained release profile. Furthermore, the development of reservoir-based systems for targeted delivery for difficult to treat applications (e.g., ocular) has resulted in potential platforms for patient therapy. PMID:22465783

  2. Electro-osmotically driven liquid delivery method and apparatus

    DOEpatents

    Rakestraw, D.J.; Anex, D.S.; Yan, C.; Dadoo, R.; Zare, R.N.

    1999-08-24

    Method and apparatus are disclosed for controlling precisely the composition and delivery of liquid at sub-{micro}L/min flow rate. One embodiment of such a delivery system is an electro-osmotically driven gradient flow delivery system that generates dynamic gradient flows with sub-{micro}L/min flow rates by merging a plurality of electro-osmotic flows. These flows are delivered by a plurality of delivery arms attached to a mixing connector, where they mix and then flow into a receiving means, preferably a column. Each inlet of the plurality of delivery arms is placed in a corresponding solution reservoir. A plurality of independent programmable high-voltage power supplies is used to apply a voltage program to each of the plurality of solution reservoirs to regulate the electro-osmotic flow in each delivery arm. The electro-osmotic flow rates in the delivery arms are changed with time according to each voltage program to deliver the required gradient profile to the column. 4 figs.

  3. Electro-osmotically driven liquid delivery method and apparatus

    DOEpatents

    Rakestraw, David J.; Anex, Deon S.; Yan, Chao; Dadoo, Rajeev; Zare, Richard N.

    1999-01-01

    Method and apparatus for controlling precisely the composition and delivery of liquid at sub-.mu.L/min flow rate. One embodiment of such a delivery system is an electro-osmotically driven gradient flow delivery system that generates dynamic gradient flows with sub-.mu.L/min flow rates by merging a plurality of electro-osmotic flows. These flows are delivered by a plurality of delivery arms attached to a mixing connector, where they mix and then flow into a receiving means, preferably a column. Each inlet of the plurality of delivery arms is placed in a corresponding solution reservoir. A plurality of independent programmable high-voltage power supplies is used to apply a voltage program to each of the plurality of solution reservoirs to regulate the electro-osmotic flow in each delivery arm. The electro-osmotic flow rates in the delivery arms are changed with time according to each voltage program to deliver the required gradient profile to the column.

  4. SU-E-T-111: Development of Proton Dosimetry System Using Fiber-Optic Cerenkov Radiation Sensor Array

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

    Son, J; Kim, M; Shin, D

    2014-06-01

    Purpose: We had developed and evaluated a new dosimetric system for proton therapy using array of fiber-optic Cerenkov radiation sensor (FOCRS) which can measure a percent depth dose (PDD) instantly. In this study, the Bragg peaks and spread out Bragg peak (SOBP) of the proton beams measured by FOCRS array were compared with those measured by an ion chamber. Methods and Method: We fabricated an optical fiber array of FOCRS in a handmade phantom which is composed of poly-methyl methacrylate (PMMA). There are 75 holes of 1mm diameter inside the phantom which is designed to be exposed in direction ofmore » beam when it is emerged in water phantom. The proton beam irradiation was carried out using IBA cyclotron PROTEUS 235 at national cancer center in Korea and a commercial data acquisition system was used to digitize the analog signal. Results: The measured Bragg peak and SOBP for the proton ranges of 7∼ 20 cm were well matched with the result from ion chamber. The comparison results show that the depth of proton beam ranges and the width of SOBP measured by array of FOCRS are comparable with the measurement from multi-layer ion chamber (MLIC) although there are some uncertainty in the measurement of FOCRS array for some specific beam ranges. Conclusion: The newly developed FOCRS array based dosimetric system for proton therapy can efficiently reduce the time and effort needed for proton beam range measurement compared to the conventional method and has the potential to be used for the proton pencil beam application.« less

  5. 33 CFR 385.17 - Project Delivery Team.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Project Delivery Team. 385.17... Processes § 385.17 Project Delivery Team. (a) In accordance with the procedures of the Corps of Engineers...,” the Corps of Engineers and the non-Federal sponsor shall form a Project Delivery Team to develop the...

  6. 33 CFR 385.17 - Project Delivery Team.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 3 2013-07-01 2013-07-01 false Project Delivery Team. 385.17... Processes § 385.17 Project Delivery Team. (a) In accordance with the procedures of the Corps of Engineers...,” the Corps of Engineers and the non-Federal sponsor shall form a Project Delivery Team to develop the...

  7. 33 CFR 385.17 - Project Delivery Team.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 3 2014-07-01 2014-07-01 false Project Delivery Team. 385.17... Processes § 385.17 Project Delivery Team. (a) In accordance with the procedures of the Corps of Engineers...,” the Corps of Engineers and the non-Federal sponsor shall form a Project Delivery Team to develop the...

  8. 33 CFR 385.17 - Project Delivery Team.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Project Delivery Team. 385.17... Processes § 385.17 Project Delivery Team. (a) In accordance with the procedures of the Corps of Engineers...,” the Corps of Engineers and the non-Federal sponsor shall form a Project Delivery Team to develop the...

  9. 33 CFR 385.17 - Project Delivery Team.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 3 2012-07-01 2012-07-01 false Project Delivery Team. 385.17... Processes § 385.17 Project Delivery Team. (a) In accordance with the procedures of the Corps of Engineers...,” the Corps of Engineers and the non-Federal sponsor shall form a Project Delivery Team to develop the...

  10. Topical drug delivery systems: a patent review.

    PubMed

    Singh Malik, Deepinder; Mital, Neeraj; Kaur, Gurpreet

    2016-01-01

    Topical administration is the favored route for local delivery of therapeutic agents due to its convenience and affordability. The specific challenge of designing a therapeutic system is to achieve an optimal concentration of a certain drug at its site of action for an appropriate duration. This review summarizes innovations from the past 3 years (2012-2015) in the field of topical drug delivery for the treatment of local infections of the vagina, nose, eye and skin. The review also throws some light on the anatomy and physiology of these organs and their various defensive barriers which affect the delivery of drugs administered topically. Topical administration has been gaining attention over the last few years. However, conventional topical drug delivery systems suffer from drawbacks such as poor retention and low bioavailability. The successful formulation of topical delivery products requires the careful manipulation of defensive barriers and selection of a soluble drug carrier. Extensive research is required to develop newer topical drug delivery systems aiming either to improve the efficacy or to reduce side effects compared to current patented systems.

  11. Helical tomotherapy with dynamic running-start-stop delivery compared to conventional tomotherapy delivery

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

    Rong, Yi, E-mail: yi.rong@osumc.edu; Chen, Yu; Lu, Weiguo

    Purpose: Despite superior target dose uniformity, helical tomotherapy{sup ®} (HT) may involve a trade-off between longitudinal dose conformity and beam-on time (BOT), due to the limitation of only three available jaw sizes with the conventional HT (1.0, 2.5, and 5.0 cm). The recently introduced dynamic running-start-stop (RSS) delivery allows smaller jaw opening at the superior and inferior ends of the target when a sharp penumbra is needed. This study compared the dosimetric performance of RSS delivery with the fixed jaw HT delivery. Methods: Twenty patient cases were selected and deidentified prior to treatment planning, including 16 common clinical cases (brain,more » head and neck (HN), lung, and prostate) and four special cases of whole brain with hippocampus avoidance (WBHA) that require a high degree of dose modulation. HT plans were generated for common clinical cases using the fixed 2.5 cm jaw width (HT2.5) and WBHA cases using 1.0 cm (HT1.0). The jaw widths for RSS were preset with a larger size (RSS5.0 vs HT2.5 and RSS2.5 vs HT1.0). Both delivery techniques were planned based on identical contours, prescriptions, and planning objectives. Dose indices for targets and critical organs were compared using dose-volume histograms, BOT, and monitor units. Results: The average BOT was reduced from 4.8 min with HT2.5 to 2.5 min with RSS5.0. Target dose homogeneity with RSS5.0 was shown comparable to HT2.5 for common clinical sites. Superior normal tissue sparing was observed in RSS5.0 for optic nerves and optic chiasm in brain and HN cases. RSS5.0 demonstrated improved dose sparing for cord and esophagus in lung cases, as well as penile bulb in prostate cases. The mean body dose was comparable for both techniques. For the WBHA cases, the target homogeneity was significantly degraded in RSS2.5 without distinct dose sparing for hippocampus, compared to HT1.0. Conclusions: Compared to the fixed jaw HT delivery, RSS combined with a larger jaw width provides faster

  12. Accuracy of sign interpreting and real-time captioning of science videos for the delivery of instruction to deaf students

    NASA Astrophysics Data System (ADS)

    Sadler, Karen L.

    2009-04-01

    The purpose of this study was to quantitatively examine the impact of third-party support service providers on the quality of science information available to deaf students in regular science classrooms. Three different videotapes that were developed by NASA for high school science classrooms were selected for the study, allowing for different concepts and vocabulary to be examined. The focus was on the accuracy of translation as measured by the number of key science words included in the transcripts (captions) or videos (interpreted). Data were collected via transcripts completed by CART (computer assisted real-time captionists) or through videos of sign language interpreters. All participants were required to listen to and translate these NASA educational videos with no prior experience with this information so as not to influence their delivery. CART personnel using captions were found to be significantly more accurate in the delivery of science words as compared to the sign language interpreters in this study.

  13. Advancements in ocular drug delivery.

    PubMed

    Weiner, Alan L; Gilger, Brian C

    2010-11-01

    This review covers both noninvasive and invasive ophthalmic drug delivery systems that can have application to therapy of veterinary ophthalmic diseases. Noninvasive approaches include gel technologies, permeation enhancement via pro-drug development, solubilization agents and nanoparticle technologies, iontophoresis, microneedles, drug-eluting contact lenses and eye misters, and microdroplets. More invasive systems include both eroding implants and noneroding technologies that encompass diffusion based systems, active pumps, intraocular lenses, suprachoroidal drug delivery, and episcleral reservoirs. In addition to addressing the physiologic challenges of achieving the necessary duration of delivery, tissue targeting and patient compliance, the commercial development factors of biocompatibility, sterilization, manufacturability and long-term stability will be discussed. © 2010 American College of Veterinary Ophthalmologists.

  14. Leisure Service Delivery Systems: Are They Adequate

    Treesearch

    Rene Fukuhara Dahl

    1992-01-01

    This presentation explores a model of service delivery ranging from direct service provision to advocacy and reports findings on the delivery mode most prevalent in park and recreation departments that serve Asian groups in their community. The implications of the role of the professional, the range of service delivery, and the manner in which ethnic groups are...

  15. Canine spontaneous glioma: A translational model system for convection-enhanced delivery

    PubMed Central

    Dickinson, Peter J.; LeCouteur, Richard A.; Higgins, Robert J.; Bringas, John R.; Larson, Richard F.; Yamashita, Yoji; Krauze, Michal T.; Forsayeth, John; Noble, Charles O.; Drummond, Daryl C.; Kirpotin, Dmitri B.; Park, John W.; Berger, Mitchel S.; Bankiewicz, Krystof S.

    2010-01-01

    Canine spontaneous intracranial tumors bear striking similarities to their human tumor counterparts and have the potential to provide a large animal model system for more realistic validation of novel therapies typically developed in small rodent models. We used spontaneously occurring canine gliomas to investigate the use of convection-enhanced delivery (CED) of liposomal nanoparticles, containing topoisomerase inhibitor CPT-11. To facilitate visualization of intratumoral infusions by real-time magnetic resonance imaging (MRI), we included identically formulated liposomes loaded with Gadoteridol. Real-time MRI defined distribution of infusate within both tumor and normal brain tissues. The most important limiting factor for volume of distribution within tumor tissue was the leakage of infusate into ventricular or subarachnoid spaces. Decreased tumor volume, tumor necrosis, and modulation of tumor phenotype correlated with volume of distribution of infusate (Vd), infusion location, and leakage as determined by real-time MRI and histopathology. This study demonstrates the potential for canine spontaneous gliomas as a model system for the validation and development of novel therapeutic strategies for human brain tumors. Data obtained from infusions monitored in real time in a large, spontaneous tumor may provide information, allowing more accurate prediction and optimization of infusion parameters. Variability in Vd between tumors strongly suggests that real-time imaging should be an essential component of CED therapeutic trials to allow minimization of inappropriate infusions and accurate assessment of clinical outcomes. PMID:20488958

  16. 3D tumor microtissues as an in vitro testing platform for microenvironmentally-triggered drug delivery systems.

    PubMed

    Brancato, Virginia; Gioiella, Filomena; Profeta, Martina; Imparato, Giorgia; Guarnieri, Daniela; Urciuolo, Francesco; Melone, Pietro; Netti, Paolo A

    2017-07-15

    Therapeutic approaches based on nanomedicine have garnered great attention in cancer research. In vitro biological models that better mimic in vivo conditions are crucial tools to more accurately predict their therapeutic efficacy in vivo. In this work, a new 3D breast cancer microtissue has been developed to recapitulate the complexity of the tumor microenvironment and to test its efficacy as screening platform for drug delivery systems. The proposed 3D cancer model presents human breast adenocarcinoma cells and cancer-associated fibroblasts embedded in their own ECM, thus showing several features of an in vivo tumor, such as overexpression of metallo-proteinases (MMPs). After demonstrating at molecular and protein level the MMP2 overexpression in such tumor microtissues, we used them to test a recently validated formulation of endogenous MMP2-responsive nanoparticles (NP). The presence of the MMP2-sensitive linker allows doxorubicin release from NP only upon specific enzymatic cleavage of the peptide. The same NP without the MMP-sensitive linker and healthy breast microtissues were also produced to demonstrate NP specificity and selectivity. Cell viability after NP treatment confirmed that controlled drug delivery is achieved only in 3D tumor microtissues suggesting that the validation of therapeutic strategies in such 3D tumor model could predict human response. A major issue of modern cancer research is the development of accurate and predictive experimental models of human tumors consistent with tumor microenvironment and applicable as screening platforms for novel therapeutic strategies. In this work, we developed and validated a new 3D microtissue model of human breast tumor as a testing platform of anti-cancer drug delivery systems. To this aim, biodegradable nanoparticles responsive to physiological changes specifically occurring in tumor microenvironment were used. Our findings clearly demonstrate that the breast tumor microtissue well recapitulates in

  17. Performance Analysis of Cyber Security Awareness Delivery Methods

    NASA Astrophysics Data System (ADS)

    Abawajy, Jemal; Kim, Tai-Hoon

    In order to decrease information security threats caused by human-related vulnerabilities, an increased concentration on information security awareness and training is necessary. There are numerous information security awareness training delivery methods. The purpose of this study was to determine what delivery method is most successful in providing security awareness training. We conducted security awareness training using various delivery methods such as text based, game based and a short video presentation with the aim of determining user preference delivery methods. Our study suggests that a combined delvery methods are better than individual secrity awareness delivery method.

  18. Highly accurate surface maps from profilometer measurements

    NASA Astrophysics Data System (ADS)

    Medicus, Kate M.; Nelson, Jessica D.; Mandina, Mike P.

    2013-04-01

    Many aspheres and free-form optical surfaces are measured using a single line trace profilometer which is limiting because accurate 3D corrections are not possible with the single trace. We show a method to produce an accurate fully 2.5D surface height map when measuring a surface with a profilometer using only 6 traces and without expensive hardware. The 6 traces are taken at varying angular positions of the lens, rotating the part between each trace. The output height map contains low form error only, the first 36 Zernikes. The accuracy of the height map is ±10% of the actual Zernike values and within ±3% of the actual peak to valley number. The calculated Zernike values are affected by errors in the angular positioning, by the centering of the lens, and to a small effect, choices made in the processing algorithm. We have found that the angular positioning of the part should be better than 1?, which is achievable with typical hardware. The centering of the lens is essential to achieving accurate measurements. The part must be centered to within 0.5% of the diameter to achieve accurate results. This value is achievable with care, with an indicator, but the part must be edged to a clean diameter.

  19. A nipple shield delivery system for oral drug delivery to breastfeeding infants: microbicide delivery to inactivate HIV.

    PubMed

    Gerrard, Stephen E; Baniecki, Mary Lynn; Sokal, David C; Morris, Mary K; Urdaneta-Hartmann, Sandra; Krebs, Fred C; Wigdahl, Brian; Abrams, Barbara F; Hanson, Carl V; Slater, Nigel K H; Edwards, Alexander D

    2012-09-15

    A new drug delivery method for infants is presented which incorporates an active pharmaceutical ingredient (API)-loaded insert into a nipple shield delivery system (NSDS). The API is released directly into milk during breastfeeding. This study investigates the feasibility of using the NSDS to deliver the microbicide sodium dodecyl sulfate (SDS), with the goal of preventing mother-to-child transmission (MTCT) of HIV during breastfeeding in low-resource settings, when there is no safer alternative for the infant but to breastfeed. SDS has been previously shown to effectively inactivate HIV in human milk. An apparatus was developed to simulate milk flow through and drug release from a NSDS. Using this apparatus milk was pulsed through a prototype device containing a non-woven fiber insert impregnated with SDS and the microbicide was rapidly released. The total SDS release from inserts ranged from 70 to 100% of the average 0.07 g load within 50 ml (the volume of a typical breastfeed). Human milk spiked with H9/HIV(IIIB) cells was also passed through the same set-up. Greater than 99% reduction of cell-associated HIV infectivity was achieved in the first 10 ml of milk. This proof of concept study demonstrates efficient drug delivery to breastfeeding infants is achievable using the NSDS. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Prior Prelabor or Intrapartum Cesarean Delivery and Risk of Placenta Previa

    PubMed Central

    Downes, Katheryne L.; Hinkle, Stefanie N.; Sjaarda, Lindsey A.; Albert, Paul S.; Grantz, Katherine L.

    2015-01-01

    Objective To examine the association between previous cesarean delivery and subsequent placenta previa while distinguishing cesarean delivery prior to onset of labor from intrapartum cesarean delivery. Study Design Retrospective cohort study of electronic medical records from 20 Utah hospitals (2002–2010) with restriction to the first two singleton deliveries of women nulliparous at study entry (n=26,987). First pregnancy delivery mode was classified as 1) vaginal (reference); 2) cesarean delivery prior to labor onset (prelabor); or 3) cesarean delivery after labor onset (intrapartum). Risk of second delivery previa was estimated by prior delivery mode using logistic regression and adjusted for maternal age, insurance, smoking, co-morbidities, prior pregnancy loss, and history of previa. Results The majority of first deliveries were vaginal (82%, n=22,142), followed by intrapartum cesarean delivery (14.6%, n=3,931), or prelabor cesarean delivery (3.4%, n=914). Incidence of second delivery previa was 0.29% (n=78) and differed by prior delivery mode: vaginal, 0.24%; prelabor cesarean delivery, 0.98%; intrapartum cesarean delivery, 0.38% (P<0.001). Relative to vaginal delivery, prior prelabor cesarean delivery was associated with an increased risk of second delivery previa (adjusted odds ratio, 2.62 [95% confidence interval, 1.24–5.56]). There was no significant association between prior intrapartum cesarean delivery and previa [adjusted odds ratio, 1.22 (95% confidence interval, 0.68–2.19)]. Conclusion Prior prelabor cesarean delivery was associated with a more than two-fold significantly increased risk of previa in the second delivery, while the approximately 20% increased risk of previa associated with prior intrapartum cesarean delivery was not significant. Although rare, the increased risk of placenta previa after prior prelabor cesarean delivery may be important when considering non-medically indicated prelabor cesarean delivery. PMID:25576818

  1. Previous prelabor or intrapartum cesarean delivery and risk of placenta previa.

    PubMed

    Downes, Katheryne L; Hinkle, Stefanie N; Sjaarda, Lindsey A; Albert, Paul S; Grantz, Katherine L

    2015-05-01

    The purpose of this study was to examine the association between previous cesarean delivery and subsequent placenta previa while distinguishing cesarean delivery before the onset of labor from intrapartum cesarean delivery. We conducted a retrospective cohort study of electronic medical records from 20 Utah hospitals (2002-2010) with restriction to the first 2 singleton deliveries of nulliparous women at study entry (n=26,987). First pregnancy delivery mode was classified as (1) vaginal (reference), (2) cesarean delivery before labor onset (prelabor), or (3) cesarean delivery after labor onset (intrapartum). Risk of second delivery previa was estimated by previous delivery mode with the use of logistic regression and was adjusted for maternal age, insurance, smoking, comorbidities, previous pregnancy loss, and history of previa. Most first deliveries were vaginal (82%; n=22,142), followed by intrapartum cesarean delivery (14.6%; n=3931), or prelabor cesarean delivery (3.4%; n=914). Incidence of second delivery previa was 0.29% (n=78) and differed by previous delivery mode: vaginal, 0.24%; prelabor cesarean delivery, 0.98%; intrapartum cesarean delivery, 0.38% (P<.001). Relative to vaginal delivery, previous prelabor cesarean delivery was associated with an increased risk of second delivery previa (adjusted odds ratio, 2.62; 95% confidence interval, 1.24-5.56). There was no significant association between previous intrapartum cesarean delivery and previa (adjusted odds ratio, 1.22; 95% confidence interval, 0.68-2.19). Previous prelabor cesarean delivery was associated with a >2-fold significantly increased risk of previa in the second delivery, although the approximately 20% increased risk of previa that was associated with previous intrapartum cesarean delivery was not significant. Although rare, the increased risk of placenta previa after previous prelabor cesarean delivery may be important when considering nonmedically indicated prelabor cesarean delivery

  2. 48 CFR 52.211-8 - Time of Delivery.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Delivery. As prescribed in 11.404(a)(2), insert the following clause: Time of Delivery (JUN 1997) (a) The... assumption that the Government will make award by __ [Contracting Officer insert date]. Each delivery date in...

  3. 48 CFR 52.211-8 - Time of Delivery.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Delivery. As prescribed in 11.404(a)(2), insert the following clause: Time of Delivery (JUN 1997) (a) The... assumption that the Government will make award by __ [Contracting Officer insert date]. Each delivery date in...

  4. 48 CFR 52.211-8 - Time of Delivery.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Delivery. As prescribed in 11.404(a)(2), insert the following clause: Time of Delivery (JUN 1997) (a) The... assumption that the Government will make award by __ [Contracting Officer insert date]. Each delivery date in...

  5. 48 CFR 52.211-8 - Time of Delivery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Delivery. As prescribed in 11.404(a)(2), insert the following clause: Time of Delivery (JUN 1997) (a) The... assumption that the Government will make award by __ [Contracting Officer insert date]. Each delivery date in...

  6. 48 CFR 52.211-8 - Time of Delivery.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Delivery. As prescribed in 11.404(a)(2), insert the following clause: Time of Delivery (JUN 1997) (a) The... assumption that the Government will make award by __ [Contracting Officer insert date]. Each delivery date in...

  7. Recent developments in leishmaniasis vaccine delivery systems.

    PubMed

    Bhowmick, Sudipta; Ali, Nahid

    2008-07-01

    The observation that recovery from infection with Leishmania confers immunity to reinfection suggests that control of leishmaniasis by vaccination may be possible. New generation vaccines, particularly those based on recombinant proteins and DNA, are found to be less immunogenic. There is an urgent need for the development of new and improved vaccine adjuvants. Based on their principal mechanisms of action, adjuvants can be broadly separated into two classes: immunostimulatory adjuvants and vaccine delivery systems. Vaccine delivery systems can carry both antigen and adjuvant for effective delivery to the antigen-presenting cells (APCs). In this article, we review the adjuvants, the delivery systems and their combinations used in the search of an effective vaccine against leishmaniasis. Based on current knowledge, cationic liposomes appear to have better prospects as effective delivery systems for developing a vaccine for leishmaniasis.

  8. Fiber laser coupled optical spark delivery system

    DOEpatents

    Yalin, Azer [Fort Collins, CO; Willson, Bryan [Fort Collins, CO; Defoort, Morgan [Fort Collins, CO; Joshi, Sachin [Fort Collins, CO; Reynolds, Adam [Fort Collins, CO

    2008-03-04

    A spark delivery system for generating a spark using a laser beam is provided, and includes a laser light source and a laser delivery assembly. The laser delivery assembly includes a hollow fiber and a launch assembly comprising launch focusing optics to input the laser beam in the hollow fiber. The laser delivery assembly further includes exit focusing optics that demagnify an exit beam of laser light from the hollow fiber, thereby increasing the intensity of the laser beam and creating a spark. Other embodiments use a fiber laser to generate a spark. Embodiments of the present invention may be used to create a spark in an engine. Yet other embodiments include collecting light from the spark or a flame resulting from the spark and conveying the light for diagnostics. Methods of using the spark delivery systems and diagnostic systems are provided.

  9. Effects of different data-editing methods on trends in race-specific preterm delivery rates, United States, 1990-2002.

    PubMed

    Qin, Cheng; Dietz, Patricia M; England, Lucinda J; Martin, Joyce A; Callaghan, William M

    2007-09-01

    -Hispanic African Americans with the LMP/CE method (1.8%), and decreased with the other methods (range 6.7-10.8%). Different approaches to editing gestational age from vital records can result in variation in preterm delivery rates and trends. Uncertainty persists around the true trends in preterm delivery, especially among African Americans. Additional research is needed to identify the approach that results in the most accurate classification of gestational age.

  10. 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

  11. Oral Insulin Delivery: How Far Are We?

    PubMed Central

    Fonte, Pedro; Araújo, Francisca; Reis, Salette; Sarmento, Bruno

    2013-01-01

    Oral delivery of insulin may significantly improve the quality of life of diabetes patients who routinely receive insulin by the subcutaneous route. In fact, compared with this administration route, oral delivery of insulin in diabetes treatment offers many advantages: higher patient compliance, rapid hepatic insulinization, and avoidance of peripheral hyperinsulinemia and other adverse effects such as possible hypoglycemia and weight gain. However, the oral delivery of insulin remains a challenge because its oral absorption is limited. The main barriers faced by insulin in the gastrointestinal tract are degradation by proteolytic enzymes and lack of transport across the intestinal epithelium. Several strategies to deliver insulin orally have been proposed, but without much clinical or commercial success. Protein encapsulation into nanoparticles is regarded as a promising alternative to administer insulin orally because they have the ability to promote insulin paracellular or transcellular transport across the intestinal mucosa. In this review, different delivery systems intended to increase the oral bioavailability of insulin will be discussed, with a special focus on nanoparticulate carrier systems, as well as the efforts that pharmaceutical companies are making to bring to the market the first oral delivery system of insulin. The toxicological and safety data of delivery systems, the clinical value and progress of oral insulin delivery, and the future prospects in this research field will be also scrutinized. PMID:23567010

  12. [Delivery of the IUGR fetus].

    PubMed

    Perrotin, F; Simon, E G; Potin, J; Laffon, M

    2013-12-01

    The purpose of this paper is to review available data regarding the management of delivery in intra uterine growth retarded fetuses and try to get recommendations for clinical obstetrical practice. Bibliographic research performed by consulting PubMed database and recommendations from scientific societies with the following words: small for gestational age, intra-uterine growth restriction, fetal growth restriction, very low birth weight infants, as well as mode of delivery, induction of labor, cesarean section and operative delivery. The diagnosis of severe IUGR justifies the orientation of the patient to a referral centre with all necessary resources for very low birth weight or premature infants Administration of corticosteroids for fetal maturation (before 34 WG) and a possible neuroprotective treatment by with magnesium sulphate (before 32-33 WG) should be discussed. Although elective caesarean section is common, there is no current evidence supporting the use of systematic cesarean section, especially when the woman is in labor. Induction of labor, even with unfavorable cervix is possible under continuous FHR monitoring, in favorable obstetric situations and in the absence of severe fetal hemodynamic disturbances. Instrumental delivery and routine episiotomy are not recommended. For caesarean section under spinal anesthesia, an adequate anesthetic management must ensure the maintenance of basal blood pressure. Compared with appropriate for gestational age fetus, IUGR fetus is at increased risk of metabolic acidosis or perinatal asphyxia during delivery. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  13. Sterile Product Packaging and Delivery Systems.

    PubMed

    Akers, Michael J

    2015-01-01

    Both conventional and more advanced product container and delivery systems are the focus of this brief article. Six different product container systems will be discussed, plus advances in primary packaging for special delivery systems and needle technology.

  14. Evaluation of Gallium as a Tracer of Exogenous Hemoglobin-Haptoglobin Complexes for Targeted Drug Delivery Applications

    NASA Astrophysics Data System (ADS)

    Xu, Shengsheng; Kaltashov, Igor A.

    2016-12-01

    Haptoglobin (Hp) is a plasma glycoprotein that generates significant interest in the drug delivery community because of its potential for delivery of antiretroviral medicines with high selectivity to macrophages and monocytes, the latent reservoirs of human immunodeficiency virus. As is the case with other therapies that exploit transport networks for targeted drug delivery, the success of the design and optimization of Hp-based therapies will critically depend on the ability to accurately localize and quantitate Hp-drug conjugates on the varying and unpredictable background of endogenous proteins having identical structure. In this work, we introduce a new strategy for detecting and quantitating exogenous Hp and Hp-based drugs with high sensitivity in complex biological samples using gallium as a tracer of this protein and inductively coupled plasma mass spectrometry (ICP MS) as a method of detection. Metal label is introduced by reconstituting hemoglobin (Hb) with gallium(III)-protoporphyrin IX followed by its complexation with Hp. Formation of the Hp/Hb assembly and its stability are evaluated with native electrospray ionization mass spectrometry. Both stable isotopes of Ga give rise to an abundant signal in ICP MS of a human plasma sample spiked with the metal-labeled Hp/Hb complex. The metal label signal exceeds the spectral interferences' contributions by more than an order of magnitude even with the concentration of the exogenous protein below 10 nM, the level that is more than adequate for the planned pharmacokinetic studies of Hp-based therapeutics.

  15. Mammalian cell delivery via aerosol deposition.

    PubMed

    Veazey, William S; Anusavice, Kenneth J; Moore, Karen

    2005-02-15

    The objective of this study was to test the hypothesis that bovine dermal fibroblasts can survive aerosol delivery via an airbrush with mean cell survival rates greater than 50%. This technology has great implications for burn and other wound therapies, for delivery of genetically altered cells in gene therapies, and for tissue engineering with tissue scaffolds. Bovine dermal fibroblasts were suspended at a concentration of 200,000 cells/mL in Hank's Balanced Salt Solution, and delivered into six-well tissue culture plates using a Badger 100G airbrush. Cells were delivered through three nozzle diameters (312, 484, and 746 microm) at five different air pressures (41, 55, 69, 96, and 124 kPa). Nine repetitions were performed for each treatment group, and cell viability was measured using trypan blue exclusion assay. Mean cell viability ranged from 37 to 94%, and depended on the combination of nozzle diameter and delivery pressure (p < 0.0001). Linear regression analysis was used to develop a stochastic model of cell delivery viability as a function of nozzle diameter and delivery air pressure. This study demonstrates the feasibility of using an airbrush to deliver viable cells in an aerosol to a substrate.

  16. Complications of Delivery Among Mothers with Spina Bifida.

    PubMed

    Shepard, Courtney L; Yan, Phyllis L; Kielb, Stephanie J; Wittmann, Daniela A; Quint, Elisabeth H; Kraft, Kate H; Hollingsworth, John M

    2018-06-13

    To determine rates and types of peripartum morbidity among delivering women with spina bifida (SB) compared to those without SB. The rates of pregnancy and delivery among women with SB have been significantly increasing. Current knowledge of peripartum outcomes for these women is limited. Using 2004-2013 National Inpatient Sample data, we identified all hospitalizations for delivery, distinguishing between women with and without SB. Using a code-based algorithm, we determined whether a complication occurred during the hospitalization. We then fit a series of multivariable logistic models to examine for associations between a complication occurrence during vaginal or cesarean delivery and a woman's SB status. We identified 38,319,814 weighted admissions for delivery, 9,516 of which were made by women with SB. Women with SB had a significantly higher rate of cesarean delivery than women without this diagnosis (53% v 32%, p<0.001). The 46.7% of women with SB who delivered vaginally did not have significantly increased odds of a complication associated with their delivery compared to women without SB [odds ratio (OR) 1.15, 95% confidence interval (CI) 0.99 to 1.34, p=0.066]. However, women with SB who underwent a cesarean delivery did have higher odds of morbidity compared to those without (OR 1.49, 95% CI 1.25 to 1.78, p<0.001). Common complications included preterm delivery, urinary tract infection, hematologic event, and blood transfusion. Compared to women without SB, those with SB deliver more frequently by cesarean section and have higher odds of morbidity associated with cesarean delivery, but not vaginal delivery. Copyright © 2018. Published by Elsevier Inc.

  17. Nanocarriers in ocular drug delivery: an update review.

    PubMed

    Wadhwa, Sheetu; Paliwal, Rishi; Paliwal, Shivani Rai; Vyas, S P

    2009-01-01

    Controlled drug delivery to eye is one of the most challenging fields of pharmaceutical research. Low drug-contact time and poor ocular bioavailability due to drainage of solution, tear turnover and its dilution or lacrimation are the problems associated with conventional systems. In addition, anatomical barriers and physiological conditions of eye are also important parameters which control designing of drug delivery systems. Nanosized carriers like micro/nano-suspensions, liposome, niosome, dendrimer, nanoparticles, ocular inserts, implants, hydrogels and prodrug approaches have been developed for this purpose. These novel systems offer manifold advantages over conventional systems as they increase the efficiency of drug delivery by improving the release profile and also reduce drug toxicity. Conventional delivery systems get diluted with tear, washed away through the lacrimal gland and usually require administering at regular time intervals whereas nanocarriers release drug at constant rate for a prolonged period of time and thus enhance its absorption and site specific delivery. This review presents an overview of the various aspects of the ocular drug delivery, with special emphasis on nanocarrier based strategies, including structure of eye, its barriers, delivery routes and the challenges/limitations associated with development of novel nanocarriers. The recent progresses in therapy of ocular disease like gene therapy have also been included so that future options should also be considered from the delivery point of view. Recent progress in the delivery of proteins and peptides via ocular route has also been incorporated for reader benefit.

  18. Nanocarriers for cancer-targeted drug delivery.

    PubMed

    Kumari, Preeti; Ghosh, Balaram; Biswas, Swati

    2016-01-01

    Nanoparticles as drug delivery system have received much attention in recent years, especially for cancer treatment. In addition to improving the pharmacokinetics of the loaded poorly soluble hydrophobic drugs by solubilizing them in the hydrophobic compartments, nanoparticles allowed cancer specific drug delivery by inherent passive targeting phenomena and adopted active targeting strategies. For this reason, nanoparticles-drug formulations are capable of enhancing the safety, pharmacokinetic profiles and bioavailability of the administered drugs leading to improved therapeutic efficacy compared to conventional therapy. The focus of this review is to provide an overview of various nanoparticle formulations in both research and clinical applications with a focus on various chemotherapeutic drug delivery systems for the treatment of cancer. The use of various nanoparticles, including liposomes, polymeric nanoparticles, dendrimers, magnetic and other inorganic nanoparticles for targeted drug delivery in cancer is detailed.

  19. Non-invasive systemic drug delivery through mucosal routes.

    PubMed

    Goyal, Amit K; Singh, Ranjit; Chauhan, Gaurav; Rath, Goutam

    2018-04-24

    Science of drug delivery has achieved tremendous milestones in the last few decades. Emergence of novel drug delivery techniques and the most popular nanotechnology directed the drug delivery to another level. Without any doubt, present technology holds the proficiency to approach even the intercellular targets. Between all these success auras, there lies wads of giant challenges. One such challenge is delivering the molecule directly to the blood stream. Parenteral route is considered as the most effective route for delivering active pharmaceutical substances, but is associated with major disadvantages of painful drug delivery. Modern drug delivery suggests several approaches to outstrip this painful phenomenon. In the present article, we represent a new systematic vision to understand the ability and desirability of mucosal sites to achieve painless drug delivery. Human mucosa presents supreme proximity to the blood circulation that one can even observe with naked eye. Advances in drug delivery provide numerous approaches to exploit the mucosa for systemic reach. However, the revolutionary success is still unapproachable, with an understandable reason of associated complexities and challenges. This manuscript summarizes the significance of each mucosal site, on the basis of anatomical-physiological grounds. Particular attention is given to rationalize the selection of disease and a suitable drug delivery approach for its treatment.

  20. Polymeric micelles for multi-drug delivery in cancer.

    PubMed

    Cho, Hyunah; Lai, Tsz Chung; Tomoda, Keishiro; Kwon, Glen S

    2015-02-01

    Drug combinations are common in cancer treatment and are rapidly evolving, moving beyond chemotherapy combinations to combinations of signal transduction inhibitors. For the delivery of drug combinations, i.e., multi-drug delivery, major considerations are synergy, dose regimen (concurrent versus sequential), pharmacokinetics, toxicity, and safety. In this contribution, we review recent research on polymeric micelles for multi-drug delivery in cancer. In concurrent drug delivery, polymeric micelles deliver multi-poorly water-soluble anticancer agents, satisfying strict requirements in solubility, stability, and safety. In sequential drug delivery, polymeric micelles participate in pretreatment strategies that "prime" solid tumors and enhance the penetration of secondarily administered anticancer agent or nanocarrier. The improved delivery of multiple poorly water-soluble anticancer agents by polymeric micelles via concurrent or sequential regimens offers novel and interesting strategies for drug combinations in cancer treatment.

  1. Oral Drug Delivery Systems Comprising Altered Geometric Configurations for Controlled Drug Delivery

    PubMed Central

    Moodley, Kovanya; Pillay, Viness; Choonara, Yahya E.; du Toit, Lisa C.; Ndesendo, Valence M. K.; Kumar, Pradeep; Cooppan, Shivaan; Bawa, Priya

    2012-01-01

    Recent pharmaceutical research has focused on controlled drug delivery having an advantage over conventional methods. Adequate controlled plasma drug levels, reduced side effects as well as improved patient compliance are some of the benefits that these systems may offer. Controlled delivery systems that can provide zero-order drug delivery have the potential for maximizing efficacy while minimizing dose frequency and toxicity. Thus, zero-order drug release is ideal in a large area of drug delivery which has therefore led to the development of various technologies with such drug release patterns. Systems such as multilayered tablets and other geometrically altered devices have been created to perform this function. One of the principles of multilayered tablets involves creating a constant surface area for release. Polymeric materials play an important role in the functioning of these systems. Technologies developed to date include among others: Geomatrix® multilayered tablets, which utilizes specific polymers that may act as barriers to control drug release; Procise®, which has a core with an aperture that can be modified to achieve various types of drug release; core-in-cup tablets, where the core matrix is coated on one surface while the circumference forms a cup around it; donut-shaped devices, which possess a centrally-placed aperture hole and Dome Matrix® as well as “release modules assemblage”, which can offer alternating drug release patterns. This review discusses the novel altered geometric system technologies that have been developed to provide controlled drug release, also focusing on polymers that have been employed in such developments. PMID:22312236

  2. Nanomedicines for Back of the Eye Drug Delivery, Gene Delivery, and Imaging

    PubMed Central

    Kompella, Uday B.; Amrite, Aniruddha C.; Ravi, Rashmi Pacha; Durazo, Shelley A.

    2013-01-01

    Treatment and management of diseases of the posterior segment of the eye such as diabetic retinopathy, retinoblastoma, retinitis pigmentosa, and choroidal neovascularization is a challenging task due to the anatomy and physiology of ocular barriers. For instance, traditional routes of drug delivery for therapeutic treatment are hindered by poor intraocular penetration and/or rapid ocular elimination. One possible approach to improve ocular therapy is to employ nanotechnology. Nanomedicines, products of nanotechnology, having at least one dimension in the nanoscale include nanoparticles, micelles, nanotubes, and dendrimers, with and without targeting ligands, are making a significant impact in the fields of ocular drug delivery, gene delivery, and imaging, the focus of this review. Key applications of nanotechnology discussed in this review include a) bioadhesive nanomedicines; b) functionalized nanomedicines that enhance target recognition and/or cell entry; c) nanomedicines capable of controlled release of the payload; d) nanomedicines capable of enhancing gene transfection and duration of transfection; f) nanomedicines responsive to stimuli including light, heat, ultrasound, electrical signals, pH, and oxidative stress; g) diversely sized and colored nanoparticles for imaging, and h) nanowires for retinal prostheses. Additionally, nanofabricated delivery systems including implants, films, microparticles, and nanoparticles are described. Although the above nanomedicines may be administered by various routes including topical, intravitreal, intravenous, transscleral, suprachoroidal, and subretinal routes, each nanomedicine should be tailored for the disease, drug, and site of administration. In addition to the nature of materials used in nanomedicine design, depending on the site of nanomedicine administration, clearance and toxicity are expected to differ. PMID:23603534

  3. Nanoparticles incorporating pH-responsive surfactants as a viable approach to improve the intracellular drug delivery.

    PubMed

    Nogueira, Daniele R; Scheeren, Laís E; Pilar Vinardell, M; Mitjans, Montserrat; Rosa Infante, M; Rolim, Clarice M B

    2015-12-01

    The pH-responsive delivery systems have brought new advances in the field of functional nanodevices and might allow more accurate and controllable delivery of specific cargoes, which is expected to result in promising applications in different clinical therapies. Here we describe a family of chitosan-TPP (tripolyphosphate) nanoparticles (NPs) for intracellular drug delivery, which were designed using two pH-sensitive amino acid-based surfactants from the family N(α),N(ε)-dioctanoyl lysine as bioactive compounds. Low and medium molecular weight chitosan (LMW-CS and MMW-CS, respectively) were used for NP preparation, and it was observed that the size distribution for NPs with LMW-CS were smaller (~168 nm) than that for NPs prepared with MMW-CS (~310 nm). Hemolysis assay demonstrated the pH-dependent biomembrane disruptional capability of the constructed NPs. The nanostructures incorporating the surfactants cause negligible membrane permeabilization at pH7.4. However, at acidic pH, prevailing in endosomes, membrane-destabilizing activity in an erythrocyte lysis assay became evident. When pH decreased to 6.6 and 5.4, hemolytic capability of chitosan NPs increased along with the raise of concentration. Furthermore, studies with cell culture showed that these pH-responsive NPs displayed low cytotoxic effects against 3T3 fibroblasts. The influence of chitosan molecular weight, chitosan to TPP weight ratio, nanoparticle size and nature of the surfactant counterion on the membrane-disruptive properties of nanoparticles was discussed in detail. Altogether, the results achieved here showed that by inserting the lysine-based amphiphiles into chitosan NPs, pH-sensitive membranolytic and potentially endosomolytic nanocarriers were developed, which, therefore, demonstrated ideal feasibility for intracellular drug delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Ultrasound-mediated drug delivery for cardiovascular disease

    PubMed Central

    Sutton, Jonathan T; Haworth, Kevin J; Pyne-Geithman, Gail; Holland, Christy K

    2014-01-01

    Introduction Ultrasound (US) has been developed as both a valuable diagnostic tool and a potent promoter of beneficial tissue bioeffects for the treatment of cardiovascular disease. These effects can be mediated by mechanical oscillations of circulating microbubbles, or US contrast agents, which may also encapsulate and shield a therapeutic agent in the bloodstream. Oscillating microbubbles can create stresses directly on nearby tissue or induce fluid effects that effect drug penetration into vascular tissue, lyse thrombi or direct drugs to optimal locations for delivery. Areas covered The present review summarizes investigations that have provided evidence for US-mediated drug delivery as a potent method to deliver therapeutics to diseased tissue for cardiovascular treatment. In particular, the focus will be on investigations of specific aspects relating to US-mediated drug delivery, such as delivery vehicles, drug transport routes, biochemical mechanisms and molecular targeting strategies. Expert opinion These investigations have spurred continued research into alternative therapeutic applications, such as bioactive gas delivery and new US technologies. Successful implementation of US-mediated drug delivery has the potential to change the way many drugs are administered systemically, resulting in more effective and economical therapeutics, and less-invasive treatments. PMID:23448121

  5. PLGA: a unique polymer for drug delivery.

    PubMed

    Kapoor, Deepak N; Bhatia, Amit; Kaur, Ripandeep; Sharma, Ruchi; Kaur, Gurvinder; Dhawan, Sanju

    2015-01-01

    Biodegradable polymers have played an important role in the delivery of drugs in a controlled and targeted manner. Polylactic-co-glycolic acid (PLGA) is one of the extensively researched synthetic biodegradable polymers due to its favorable properties. It is also known as a 'Smart Polymer' due to its stimuli sensitive behavior. A wide range of PLGA-based drug delivery systems have been reported for the treatment or diagnosis of various diseases and disorders. The present review provides an overview of the chemistry, physicochemical properties, biodegradation behavior, evaluation parameters and applications of PLGA in drug delivery. Different drug-polymer combinations developed into drug delivery or carrier systems are enumerated and discussed.

  6. Communications data delivery system analysis task 2 report : high-level options for secure communications data delivery systems.

    DOT National Transportation Integrated Search

    2012-05-16

    This Communications Data Delivery System Analysis Task 2 report describes and analyzes options for Vehicle to Vehicle (V2V) and Vehicle to Infrastructure (V2I) communications data delivery systems using various communication media (Dedicated Short Ra...

  7. Transdermal Drug Delivery: Opportunities and Challenges for Controlled Delivery of Therapeutic Agents Using Nanocarriers.

    PubMed

    Kurmi, Balak Das; Tekchandani, Pawan; Paliwal, Rishi; Paliwal, Shivani Rai

    2017-01-01

    Transdermal drug delivery represents an extremely attractive and innovative route across the skin owing to the possibility for achieving systemic effect of drugs. The present scenario demands a special focus on developing safe medicine with minimized toxic adverse effects related to most of the pharmacologically active agents. Transdermal drug delivery would be a focal paradigm which provides patient convenience, first-pass hepatic metabolism avoidance, local targeting and reduction in toxic effect related to various categories of drugs like, analgesics, antiinflammatory, antibiotics, antiviral, anaesthetic, anticancer etc. Even this route has challenges due to highly organized structure of skin which acts as a main barrier to penetration of drug via the skin. Several alternative possible strategies are available which overcome these barriers, including use of penetration enhancer, eletroporation, iontophoresis and various nanotechnologically developed nanocarrier systems. The latest one includes employing liposome, dendrimers, nanoparticles, ethosome, carbon nanotube and many more to avoid associated limitations of conventional formulations. Numerous transdermal products such as Estrasorb, Diractin, VivaGel®, Daytrana®, Aczone, Sileryst® are available in the market having a novel strategy to achieve higher penetration of drugs. This encourages formulation fraternity to develop structurally deformable and stable nanocarriers as an alternative approach for controlled and reliable drug delivery across the skin barrier. In this review, we will discuss nanocarriers mediated approaches that come-up with the solutions to the different challenges towards transdermal drug delivery, its clinical importance and latest insight to research in it. The reports presented in this review confirm the wide application of nanocarriers for transdermal delivery of drug/gene. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Variation in vaginal breech delivery rates by hospital type.

    PubMed

    Gregory, K D; Korst, L M; Krychman, M; Cane, P; Platt, L D

    2001-03-01

    To relate vaginal breech delivery rates to the following hospital types: public, health maintenance organization, private teaching, or private nonteaching. In a retrospective study using administrative discharge data from Los Angeles County, California, we calculated the vaginal breech delivery rates of singleton breech deliveries during calendar years 1988 and 1991. Ten thousand four hundred breech deliveries were identified, 8988 (86.4%) term and 1412 (13.6%) preterm. Twelve percent (1252 of 10,400) were vaginal deliveries (10.1% term and 24.5% preterm). Term vaginal breech deliveries varied by hospital type and were more frequent in public hospitals (28.4%, 95% confidence interval [CI] 26.1%, 30.7%) and less frequent in private nonteaching hospitals (5.4%, 95% CI 4.8%, 5.9%). Term vaginal deliveries were 2.4 to 11.3 times more likely among black women and 1.3 to 6.3 times more likely for Hispanic women across all hospital types, compared with white women in private nonteaching hospitals. There was no difference in the proportion of preterm vaginal breech deliveries by hospital type (mean 24.5%). However, with the exception of public hospitals, the proportion of vaginal breech deliveries for both term and preterm deliveries varied significantly by ethnicity. The use of vaginal breech delivery varied by hospital type and patient ethnicity. Within private teaching and nonteaching hospitals, vaginal breech delivery was more likely for black women than for women of other ethnic groups. Further study is needed to understand the hospital policies or organizational factors, as well as the patient-related sociocultural and clinical factors, that contribute to those differences.

  9. A spatial model to quantify the mortality impact of service delivery in Sub-Saharan Africa: an ecological design utilizing data from South Africa

    PubMed Central

    2013-01-01

    Background Sub Saharan Africa is confronted with a wide range of interlinked health and economic problems that include high levels of mortality and poor service delivery. The objective of the paper is to develop a spatial model for Sub-Saharan Africa that can quantify the mortality impact of (poor) service delivery at sub-district level in order to integrate related health and local level policy interventions. In this regard, an expanded composite service delivery index was developed, and the data were analysed using a Bayesian Poisson spatial model. Results The results indicate significant differences in the risk of mortality and poor service delivery at sub-district level. In particular, the results indicate clusters of high mortality and poor service delivery in two of the bigger, poorer provinces with large rural communities. Conversely, two of the wealthier provinces have lower levels of mortality and higher levels of service delivery, but income inequality is more widespread. The bivariate and multivariate models, moreover, reflect significant positive linkages (p < 0.01) between increased mortality and poor service delivery after adjusting for HIV/AIDS, income inequality, population density and the protective influence of metropolitan areas. Finally, the hypothesized provision of a basket of services reduced the mortality rate in South Africa’s 248 sub-districts by an average of 5.3 (0.3-15.4) deaths per 1000. Conclusion The results indicate that the model can accurately plot mortality and service delivery “hotspots’ at sub-district level, as well as explain their associations and causality. A mortality reduction index shows that mortality in the highest risk sub-districts can be reduced by as much as 15.4 deaths per 1000 by providing a range of basic services. The ability to use the model in a wider SSA context and elsewhere is also feasible given the innovative use of available databases. Finally, the paper illustrates the importance of

  10. A spatial model to quantify the mortality impact of service delivery in Sub-Saharan Africa: an ecological design utilizing data from South Africa.

    PubMed

    Sartorius, Kurt; Sartorius, Benn K D

    2013-02-20

    Sub Saharan Africa is confronted with a wide range of interlinked health and economic problems that include high levels of mortality and poor service delivery. The objective of the paper is to develop a spatial model for Sub-Saharan Africa that can quantify the mortality impact of (poor) service delivery at sub-district level in order to integrate related health and local level policy interventions. In this regard, an expanded composite service delivery index was developed, and the data were analysed using a Bayesian Poisson spatial model. The results indicate significant differences in the risk of mortality and poor service delivery at sub-district level. In particular, the results indicate clusters of high mortality and poor service delivery in two of the bigger, poorer provinces with large rural communities. Conversely, two of the wealthier provinces have lower levels of mortality and higher levels of service delivery, but income inequality is more widespread. The bivariate and multivariate models, moreover, reflect significant positive linkages (p < 0.01) between increased mortality and poor service delivery after adjusting for HIV/AIDS, income inequality, population density and the protective influence of metropolitan areas. Finally, the hypothesized provision of a basket of services reduced the mortality rate in South Africa's 248 sub-districts by an average of 5.3 (0.3-15.4) deaths per 1000. The results indicate that the model can accurately plot mortality and service delivery "hotspots' at sub-district level, as well as explain their associations and causality. A mortality reduction index shows that mortality in the highest risk sub-districts can be reduced by as much as 15.4 deaths per 1000 by providing a range of basic services. The ability to use the model in a wider SSA context and elsewhere is also feasible given the innovative use of available databases. Finally, the paper illustrates the importance of developing policy in SSA that can

  11. Drug delivery with microsecond laser pulses into gelatin

    NASA Astrophysics Data System (ADS)

    Shangguan, Hanqun; Casperson, Lee W.; Shearin, Alan; Gregory, Kenton W.; Prahl, Scott A.

    1996-07-01

    Photoacoustic drug delivery is a technique for localized drug delivery by laser-induced hydrodynamic pressure following cavitation bubble expansion and collapse. Photoacoustic drug delivery was investigated on gelatin-based thrombus models with planar and cylindrical geometries by use of one microsecond laser pulses. Solutions of a hydrophobic dye in mineral oil permitted monitoring of delivered colored oil into clear gelatin-based thrombus models. Cavitation bubble development and photoacoustic drug delivery were visualized with flash photography. This study demonstrated that cavitation is the governing mechanism for photoacoustic drug delivery, and the deepest penetration of colored oil in gels followed the bubble collapse. Spatial distribution measurements revealed that colored oil could be driven a few millimeters into the gels in both axial and radial directions, and the penetration was less than 500 mu m when the gelatin structure was not fractured. localized drug delivery, cavitation bubble, laser thrombolysis.

  12. Solid lipid nanoparticles for ocular drug delivery.

    PubMed

    Seyfoddin, Ali; Shaw, John; Al-Kassas, Raida

    2010-01-01

    Ocular drug delivery remains challenging because of the complex nature and structure of the eye. Conventional systems, such as eye drops and ointments, are inefficient, whereas systemic administration requires high doses resulting in significant toxicity. There is a need to develop novel drug delivery carriers capable of increasing ocular bioavailability and decreasing both local and systemic cytotoxicity. Nanotechnology is expected to revolutionize ocular drug delivery. Many nano-structured systems have been employed for ocular drug delivery and yielded some promising results. Solid lipid nanoparticles (SLNs) have been looked at as a potential drug carrier system since the 1990s. SLNs do not show biotoxicity as they are prepared from physiological lipids. SLNs are especially useful in ocular drug delivery as they can enhance the corneal absorption of drugs and improve the ocular bioavailability of both hydrophilic and lipophilic drugs. SLNs have another advantage of allowing autoclave sterilization, a necessary step towards formulation of ocular preparations. This review outlines in detail the various production, characterization, sterilization, and stabilization techniques for SLNs. In-vitro and in-vivo methods to study the drug release profile of SLNs have been explained. Special attention has been given to the nature of lipids and surfactants commonly used for SLN production. A summary of previous studies involving the use of SLNs in ocular drug delivery is provided, along with a critical evaluation of SLNs as a potential ocular delivery system.

  13. Delivery of primary health care to persons who are socio-economically disadvantaged: does the organizational delivery model matter?

    PubMed Central

    2013-01-01

    Background As health systems evolve, it is essential to evaluate their impact on the delivery of health services to socially disadvantaged populations. We evaluated the delivery of primary health services for different socio-economic groups and assessed the performance of different organizational models in terms of equality of health care delivery in Ontario, Canada. Methods Cross sectional study of 5,361 patients receiving care from primary care practices using Capitation, Salaried or Fee-For-Service remuneration models. We assessed self-reported health status of patients, visit duration, number of visits per year, quality of health service delivery, and quality of health promotion. We used multi-level regressions to study service delivery across socio-economic groups and within each delivery model. Identified disparities were further analysed using a t-test to determine the impact of service delivery model on equity. Results Low income individuals were more likely to be women, unemployed, recent immigrants, and in poorer health. These individuals were overrepresented in the Salaried model, reported more visits/year across all models, and tended to report longer visits in the Salaried model. Measures of primary care services generally did not differ significantly between low and higher income/education individuals; when they did, the difference favoured better service delivery for at-risk groups. At-risk patients in the Salaried model were somewhat more likely to report health promotion activities than patients from Capitation and Fee-For-Service models. At-risk patients from Capitation models reported a smaller increase in the number of additional clinic visits/year than Fee-For-Service and Salaried models. At-risk patients reported better first contact accessibility than their non-at-risk counterparts in the Fee-For-Service model only. Conclusions Primary care service measures did not differ significantly across socio-economic status or primary care delivery

  14. Delivery of primary health care to persons who are socio-economically disadvantaged: does the organizational delivery model matter?

    PubMed

    Dahrouge, Simone; Hogg, William; Ward, Natalie; Tuna, Meltem; Devlin, Rose Anne; Kristjansson, Elizabeth; Tugwell, Peter; Pottie, Kevin

    2013-12-17

    As health systems evolve, it is essential to evaluate their impact on the delivery of health services to socially disadvantaged populations. We evaluated the delivery of primary health services for different socio-economic groups and assessed the performance of different organizational models in terms of equality of health care delivery in Ontario, Canada. Cross sectional study of 5,361 patients receiving care from primary care practices using Capitation, Salaried or Fee-For-Service remuneration models. We assessed self-reported health status of patients, visit duration, number of visits per year, quality of health service delivery, and quality of health promotion. We used multi-level regressions to study service delivery across socio-economic groups and within each delivery model. Identified disparities were further analysed using a t-test to determine the impact of service delivery model on equity. Low income individuals were more likely to be women, unemployed, recent immigrants, and in poorer health. These individuals were overrepresented in the Salaried model, reported more visits/year across all models, and tended to report longer visits in the Salaried model. Measures of primary care services generally did not differ significantly between low and higher income/education individuals; when they did, the difference favoured better service delivery for at-risk groups. At-risk patients in the Salaried model were somewhat more likely to report health promotion activities than patients from Capitation and Fee-For-Service models. At-risk patients from Capitation models reported a smaller increase in the number of additional clinic visits/year than Fee-For-Service and Salaried models. At-risk patients reported better first contact accessibility than their non-at-risk counterparts in the Fee-For-Service model only. Primary care service measures did not differ significantly across socio-economic status or primary care delivery models. In Ontario, capitation

  15. 29 CFR 780.153 - Delivery “to storage.”

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 3 2012-07-01 2012-07-01 false Delivery âto storage.â 780.153 Section 780.153 Labor... of Agriculture Specified Delivery Operations § 780.153 Delivery “to storage.” The term “delivery to storage” includes taking agricultural or horticultural commodities, dairy products, livestock, bees or...

  16. 29 CFR 780.153 - Delivery “to storage.”

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 3 2011-07-01 2011-07-01 false Delivery âto storage.â 780.153 Section 780.153 Labor... of Agriculture Specified Delivery Operations § 780.153 Delivery “to storage.” The term “delivery to storage” includes taking agricultural or horticultural commodities, dairy products, livestock, bees or...

  17. 29 CFR 780.153 - Delivery “to storage.”

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 3 2013-07-01 2013-07-01 false Delivery âto storage.â 780.153 Section 780.153 Labor... of Agriculture Specified Delivery Operations § 780.153 Delivery “to storage.” The term “delivery to storage” includes taking agricultural or horticultural commodities, dairy products, livestock, bees or...

  18. 29 CFR 780.153 - Delivery “to storage.”

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 3 2014-07-01 2014-07-01 false Delivery âto storage.â 780.153 Section 780.153 Labor... of Agriculture Specified Delivery Operations § 780.153 Delivery “to storage.” The term “delivery to storage” includes taking agricultural or horticultural commodities, dairy products, livestock, bees or...

  19. Polymer nanogels: a versatile nanoscopic drug delivery platform

    PubMed Central

    Chacko, Reuben T.; Ventura, Judy; Zhuang, Jiaming; Thayumanavan, S.

    2012-01-01

    In this review we put the spotlight on crosslinked polymer nanogels, a promising platform that has the characteristics of an “ideal” drug delivery vehicle. Some of the key aspects of drug delivery vehicle design like stability, response to biologically relevant stimuli, passive targeting, active targeting, toxicity and ease of synthesis are discussed. We discuss several delivery systems in this light and highlight some examples of systems, which satisfy some or all of these design requirements. In particular, we point to the advantages that crosslinked polymeric systems bring to drug delivery. We review some of the synthetic methods of nanogel synthesis and conclude with the diverse applications in drug delivery where nanogels have been fruitfully employed. PMID:22342438

  20. Modeling the Delivery Physiology of Distributed Learning Systems.

    ERIC Educational Resources Information Center

    Paquette, Gilbert; Rosca, Ioan

    2003-01-01

    Discusses instructional delivery models and their physiology in distributed learning systems. Highlights include building delivery models; types of delivery models, including distributed classroom, self-training on the Web, online training, communities of practice, and performance support systems; and actors (users) involved, including experts,…

  1. 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.

  2. Lunar Cycle Influences Spontaneous Delivery in Cows

    PubMed Central

    Yonezawa, Tomohiro; Uchida, Mona; Tomioka, Michiko; Matsuki, Naoaki

    2016-01-01

    There is a popular belief that the lunar cycle influences spontaneous delivery in both humans and cattle. To assess this relationship, we investigated the synodic distribution of spontaneous deliveries in domestic Holstein cows. We used retrospective data from 428 spontaneous, full-term deliveries within a three-year period derived from the calving records of a private farm in Hokkaido, Japan. Spontaneous birth frequency increased uniformly from the new moon to the full moon phase and decreased until the waning crescent phase. There was a statistically significant peak between the waxing gibbous and full moon phases compared with those between the last quarter and the waning crescent. These changes were clearly observed in deliveries among multiparous cows, whereas they were not evident in deliveries among nulliparous cows. These data suggest the utility of dairy cows as models for bio-meteorological studies, and indicate that monitoring lunar phases may facilitate comprehensive understanding of parturition. PMID:27580019

  3. Smart Drug Delivery Systems in Cancer Therapy.

    PubMed

    Unsoy, Gozde; Gunduz, Ufuk

    2018-02-08

    Smart nanocarriers have been designed for tissue-specific targeted drug delivery, sustained or triggered drug release and co-delivery of synergistic drug combinations to develop safer and more efficient therapeutics. Advances in drug delivery systems provide reduced side effects, longer circulation half-life and improved pharmacokinetics. Smart drug delivery systems have been achieved successfully in the case of cancer. These nanocarriers can serve as an intelligent system by considering the differences of tumor microenvironment from healthy tissue, such as low pH, low oxygen level, or high enzymatic activity of matrix metalloproteinases. The performance of anti-cancer agents used in cancer diagnosis and therapy is improved by enhanced cellular internalization of smart nanocarriers and controlled drug release. Here, we review targeting, cellular internalization; controlled drug release and toxicity of smart drug delivery systems. We are also emphasizing the stimulus responsive controlled drug release from smart nanocarriers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Drug Delivery Research: The Invention Cycle.

    PubMed

    Park, Kinam

    2016-07-05

    Controlled drug delivery systems have been successful in introducing improved formulations for better use of existing drugs and novel delivery of biologicals. The initial success of producing many oral products and some injectable depot formulations, however, reached a plateau, and the progress over the past three decades has been slow. This is likely due to the difficulties of formulating hydrophilic, high molecular weight drugs, such as proteins and nucleic acids, for targeting specific cells, month-long sustained delivery, and pulsatile release. Since the approaches that have served well for delivery of small molecules are not applicable to large molecules, it is time to develop new methods for biologicals. The process of developing future drug delivery systems, termed as the invention cycle, is proposed, and it starts with clearly defining the problems for developing certain formulations. Once the problems are well-defined, creative imagination examines all potential options and selects the best answer and alternatives. Then, innovation takes over to generate unique solutions for developing new formulations that resolve the previously identified problems. Ultimately, the new delivery systems will have to go through a translational process to produce the final formulations for clinical use. The invention cycle also emphasizes examining the reasons for success of certain formulations, not just the reasons for failure of many systems. Implementation of the new invention cycle requires new mechanisms of funding the younger generation of scientists and a new way of identifying their achievements, thereby releasing them from the burden of short-termism.

  5. 49 CFR 663.35 - Post-delivery Buy America certification.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 7 2010-10-01 2010-10-01 false Post-delivery Buy America certification. 663.35...-Delivery Audits § 663.35 Post-delivery Buy America certification. For purposes of this part, a post-delivery Buy America certification is a certification that the recipient keeps on file that— (a) There is a...

  6. 49 CFR 663.35 - Post-delivery Buy America certification.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 7 2014-10-01 2014-10-01 false Post-delivery Buy America certification. 663.35...-Delivery Audits § 663.35 Post-delivery Buy America certification. For purposes of this part, a post-delivery Buy America certification is a certification that the recipient keeps on file that— (a) There is a...

  7. 49 CFR 663.35 - Post-delivery Buy America certification.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 7 2012-10-01 2012-10-01 false Post-delivery Buy America certification. 663.35...-Delivery Audits § 663.35 Post-delivery Buy America certification. For purposes of this part, a post-delivery Buy America certification is a certification that the recipient keeps on file that— (a) There is a...

  8. 49 CFR 663.35 - Post-delivery Buy America certification.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 7 2013-10-01 2013-10-01 false Post-delivery Buy America certification. 663.35...-Delivery Audits § 663.35 Post-delivery Buy America certification. For purposes of this part, a post-delivery Buy America certification is a certification that the recipient keeps on file that— (a) There is a...

  9. 49 CFR 663.35 - Post-delivery Buy America certification.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 7 2011-10-01 2011-10-01 false Post-delivery Buy America certification. 663.35...-Delivery Audits § 663.35 Post-delivery Buy America certification. For purposes of this part, a post-delivery Buy America certification is a certification that the recipient keeps on file that— (a) There is a...

  10. Recent advances in chitosan-based nanoparticulate pulmonary drug delivery

    NASA Astrophysics Data System (ADS)

    Islam, Nazrul; Ferro, Vito

    2016-07-01

    The advent of biodegradable polymer-encapsulated drug nanoparticles has made the pulmonary route of administration an exciting area of drug delivery research. Chitosan, a natural biodegradable and biocompatible polysaccharide has received enormous attention as a carrier for drug delivery. Recently, nanoparticles of chitosan (CS) and its synthetic derivatives have been investigated for the encapsulation and delivery of many drugs with improved targeting and controlled release. Herein, recent advances in the preparation and use of micro-/nanoparticles of chitosan and its derivatives for pulmonary delivery of various therapeutic agents (drugs, genes, vaccines) are reviewed. Although chitosan has wide applications in terms of formulations and routes of drug delivery, this review is focused on pulmonary delivery of drug-encapsulated nanoparticles of chitosan and its derivatives. In addition, the controversial toxicological effects of chitosan nanoparticles for lung delivery will also be discussed.

  11. Implementation of a Flexible Online Delivery Model to Replace a Traditional Face-to-Face Delivery of a PGCE ICT Module

    ERIC Educational Resources Information Center

    Watts, Martin

    2007-01-01

    This paper describes aspects of the planning and delivery of a 10 credit module to learners participating in a full-time, Secondary Informational Communication Technology (ICT) PGCE course and the decision to replace an existing face-to-face delivery with a flexible, online delivery. The paper focuses upon four associated aspects of the module,…

  12. Challenges and opportunities in dermal/transdermal delivery

    PubMed Central

    Paudel, Kalpana S; Milewski, Mikolaj; Swadley, Courtney L; Brogden, Nicole K; Ghosh, Priyanka; Stinchcomb, Audra L

    2010-01-01

    Transdermal drug delivery is an exciting and challenging area. There are numerous transdermal delivery systems currently available on the market. However, the transdermal market still remains limited to a narrow range of drugs. Further advances in transdermal delivery depend on the ability to overcome the challenges faced regarding the permeation and skin irritation of the drug molecules. Emergence of novel techniques for skin permeation enhancement and development of methods to lessen skin irritation would widen the transdermal market for hydrophilic compounds, macromolecules and conventional drugs for new therapeutic indications. As evident from the ongoing clinical trials of a wide variety of drugs for various clinical conditions, there is a great future for transdermal delivery of drugs. PMID:21132122

  13. Stimuli-responsive nanomaterials for therapeutic protein delivery.

    PubMed

    Lu, Yue; Sun, Wujin; Gu, Zhen

    2014-11-28

    Protein therapeutics have emerged as a significant role in treatment of a broad spectrum of diseases, including cancer, metabolic disorders and autoimmune diseases. The efficacy of protein therapeutics, however, is limited by their instability, immunogenicity and short half-life. In order to overcome these barriers, tremendous efforts have recently been made in developing controlled protein delivery systems. Stimuli-triggered release is an appealing and promising approach for protein delivery and has made protein delivery with both spatiotemporal- and dosage-controlled manners possible. This review surveys recent advances in controlled protein delivery of proteins or peptides using stimuli-responsive nanomaterials. Strategies utilizing both physiological and external stimuli are introduced and discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Stimuli-Responsive Nanomaterials for Therapeutic Protein Delivery

    PubMed Central

    Lu, Yue; Sun, Wujin; Gu, Zhen

    2014-01-01

    Protein therapeutics have emerged as a significant role in treatment of a broad spectrum of diseases, including cancer, metabolic disorders and autoimmune diseases. The efficacy of protein therapeutics, however, is limited by their instability, immunogenicity and short half-life. In order to overcome these barriers, tremendous efforts have recently been made in developing controlled protein delivery systems. Stimuli-triggered release is an appealing and promising approach for protein delivery and has made protein delivery with both spatiotemporal- and dosage-controlled manners possible. This review surveys recent advances in controlled protein delivery of proteins or peptides using stimuli-responsive nanomaterials. Strategies utilizing both physiological and external stimuli are introduced and discussed. PMID:25151983

  15. Research on JD e-commerce's delivery model

    NASA Astrophysics Data System (ADS)

    Fan, Zhiguo; Ma, Mengkun; Feng, Chaoying

    2017-03-01

    E-commerce enterprises represented by JD have made a great contribution to the economic growth and economic development of our country. Delivery, as an important part of logistics, has self-evident importance. By establishing efficient and perfect self-built logistics systems and building good cooperation models with third-party logistics enterprises, e-commerce enterprises have created their own logistics advantages. Characterized by multi-batch and small-batch, e-commerce is much more complicated than traditional transaction. It's not easy to decide which delivery model e-commerce enterprises should adopt. Having e-commerce's logistics delivery as the main research object, this essay aims to find a more suitable logistics delivery model for JD's development.

  16. Smart Polymers in Nasal Drug Delivery

    PubMed Central

    Chonkar, Ankita; Nayak, Usha; Udupa, N.

    2015-01-01

    Nasal drug delivery has now been recognized as a promising route for drug delivery due to its capability of transporting a drug to systemic circulation and central nervous system. Though nasal mucosa offers improved bioavailability and quick onset of action of the drug, main disadvantage associated with nasal drug delivery is mucocilliary clearance due to which drug particles get cleared from the nose before complete absorption through nasal mucosa. Therefore, mucoadhesive polymeric approach can be successfully used to enhance the retention of the drug on nasal mucosal surface. Here, some of the aspects of the stimuli responsive polymers have been discussed which possess liquid state at the room temperature and in response to nasal temperature, pH and ions present in mucous, can undergo in situ gelation in nasal cavity. In this review, several temperature responsive, pH responsive and ion responsive polymers used in nasal delivery, their gelling mechanisms have been discussed. Smart polymers not only able to enhance the retention of the drug in nasal cavity but also provide controlled release, ease of administration, enhanced permeation of the drug and protection of the drug from mucosal enzymes. Thus smart polymeric approach can be effectively used for nasal delivery of peptide drugs, central nervous system dugs and hormones. PMID:26664051

  17. Obstetric management in vacuum-extraction deliveries.

    PubMed

    Ahlberg, Mia; Saltvedt, Sissel; Ekéus, Cecilia

    2016-06-01

    The aim of this observational study was to describe the obstetric management in vacuum extraction (VE) deliveries and to compare these findings to instructions in clinical guidelines on VE. In 2013, detailed data on management of 600 VE cases were consecutively collected from six different delivery units in Sweden. Each unit also contributed their own clinical VE guideline. In total, 93% of the VEs ended with a vaginal delivery while 7% failed and were converted to an emergency cesarean section. In 2.3% extraction time exceeded 20 minutes, and in 6% more than six pulls were used to deliver the fetus. Cup detachment occurred in 14.6%, and fundal pressure was used in 11% of the deliveries. In 2.3%, fetal station was assessed as above the level of the maternal ischial spines. The clinical guidelines on VE varied in scope and content between units, and were often incomplete according to best practice. The vast majority of the VEs were conducted in accordance with safety recommendations. However, in a few extractions, safety rules were disregarded and more than six pulls or an extraction time of more than 20 minutes were used to complete the delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Microneedles for intradermal and transdermal delivery

    PubMed Central

    Tuan-Mahmood, Tuan-Mazlelaa; McCrudden, Maeliosa T.C.; Torrisi, Barbara M.; McAlister, Emma; Garland, Martin J; Singh, Thakur Raghu Raj; Donnelly, Ryan F

    2014-01-01

    The formidable barrier properties of the uppermost layer of the skin, the stratum corneum impose significant limitations for successful systemic delivery of a broad range of therapeutic molecules, particularly macromolecules and genetic material. Microneedle delivery has been proposed as a strategy to breach the SC barrier function in order to facilitate effective transport of molecules across the skin. This strategy involves the use of micron sized needles fabricated from different materials and using different geometries to create transient aqueous conduits across the skin. Microneedles in isolation, or in combination with other enhancing strategies, have been shown to dramatically enhance the skin permeability of numerous therapeutic molecules including biopharmaceuticals either in vitro, ex vivo or in vivo. Progress in the areas of microneedle design, development and manufacture have proven promising in terms of the potential use of this emerging delivery method in clinical applications such as insulin delivery, transcutaneous immunisations and cutaneous gene delivery. This review article focuses on recent and potential future developments in microneedle technologies. This will include the detailing of progress made in microneedle design, an exploration of the challenges faced in this field and potential forward strategies to embrace the exploitation of microneedle methodologies, while considering the inherent safety aspects of such therapeutic tools. PMID:23680534

  19. Transorbital therapy delivery: phantom testing

    NASA Astrophysics Data System (ADS)

    Ingram, Martha-Conley; Atuegwu, Nkiruka; Mawn, Louise; Galloway, Robert L.

    2011-03-01

    We have developed a combined image-guided and minimally invasive system for the delivery of therapy to the back of the eye. It is composed of a short 4.5 mm diameter endoscope with a magnetic tracker embedded in the tip. In previous work we have defined an optimized fiducial placement for accurate guidance to the back of the eye and are now moving to system testing. The fundamental difficulty in testing performance is establishing a target in a manner which closely mimics the physiological task. We have to have a penetrable material which obscures line of sight, similar to the orbital fat. In addition we need to have some independent measure of knowing when a target has been reached to compare to the ideal performance. Lastly, the target cannot be rigidly attached to the skull phantom since the optic nerve lies buried in the orbital fat. We have developed a skull phantom with white cloth stellate balls supporting a correctly sized globe. Placed in the white balls are red, blue, orange and yellow balls. One of the colored balls has been soaked in barium to make it bright on CT. The user guides the tracked endoscope to the target as defined by the images and tells us its color. We record task accuracy and time to target. We have tested this with 28 residents, fellows and attending physicians. Each physician performs the task twice guided and twice unguided. Results will be presented.

  20. 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.

  1. Nanomaterials in cancer-therapy drug delivery system.

    PubMed

    Zhang, Gen; Zeng, Xin; Li, Ping

    2013-05-01

    Nanomaterials can enhance the delivery and treatment efficiency of anti-cancer drugs, and the mechanisms of the tumor-reducing activity of nanomaterials with cancer drug have been investigated. The task for drug to reach pathological areas has facilitated rapid advances in nanomedicine. Herein, we summarize promising findings with respect to cancer therapeutics based on nano-drug delivery vectors. Relatively high toxicity of uncoated nanoparticles restricts the use of these materials in humans. In order to reduce toxicity, many approaches have focused on the encapsulation of nanoparticles with biocompatible materials. Efficient delivery systems have been developed that utilized nanoparticles loaded with high dose of cancer drug in the presence of bilayer molecules. Well-established nanotechnologies have been designed for drug delivery with specific bonding. Surface-modified nanoparticles as vehicles for drug delivery system that contains multiple nano-components, each specially designed to achieve aimed task for the emerging application delivery of therapeutics. Drug-coated polymer nanoparticles could efficiently increase the intracellular accumulation of anti-cancer drugs. This review also introduces the nanomaterials with drug on the induction of apoptosis in cancer cells in vitro and in vivo. Direct interactions between the particles and cellular molecules to cause adverse biological responses are also discussed.

  2. 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.

  3. Tumor Penetrating Theranostic Nanoparticles for Enhancement of Targeted and Image-guided Drug Delivery into Peritoneal Tumors following Intraperitoneal Delivery.

    PubMed

    Gao, Ning; Bozeman, Erica N; Qian, Weiping; Wang, Liya; Chen, Hongyu; Lipowska, Malgorzata; Staley, Charles A; Wang, Y Andrew; Mao, Hui; Yang, Lily

    2017-01-01

    The major obstacles in intraperitoneal (i.p.) chemotherapy of peritoneal tumors are fast absorption of drugs into the blood circulation, local and systemic toxicities, inadequate drug penetration into large tumors, and drug resistance. Targeted theranostic nanoparticles offer an opportunity to enhance the efficacy of i.p. therapy by increasing intratumoral drug delivery to overcome resistance, mediating image-guided drug delivery, and reducing systemic toxicity. Herein we report that i.p. delivery of urokinase plasminogen activator receptor (uPAR) targeted magnetic iron oxide nanoparticles (IONPs) led to intratumoral accumulation of 17% of total injected nanoparticles in an orthotopic mouse pancreatic cancer model, which was three-fold higher compared with intravenous delivery. Targeted delivery of near infrared dye labeled IONPs into orthotopic tumors could be detected by non-invasive optical and magnetic resonance imaging. Histological analysis revealed that a high level of uPAR targeted, PEGylated IONPs efficiently penetrated into both the peripheral and central tumor areas in the primary tumor as well as peritoneal metastatic tumor. Improved theranostic IONP delivery into the tumor center was not mediated by nonspecific macrophage uptake and was independent from tumor blood vessel locations. Importantly, i.p. delivery of uPAR targeted theranostic IONPs carrying chemotherapeutics, cisplatin or doxorubicin, significantly inhibited the growth of pancreatic tumors without apparent systemic toxicity. The levels of proliferating tumor cells and tumor vessels in tumors treated with the above theranostic IONPs were also markedly decreased. The detection of strong optical signals in residual tumors following i.p. therapy suggested the feasibility of image-guided surgery to remove drug-resistant tumors. Therefore, our results support the translational development of i.p. delivery of uPAR-targeted theranostic IONPs for image-guided treatment of peritoneal tumors.

  4. Controlled drug delivery systems: past forward and future back.

    PubMed

    Park, Kinam

    2014-09-28

    Controlled drug delivery technology has progressed over the last six decades. This progression began in 1952 with the introduction of the first sustained release formulation. The 1st generation of drug delivery (1950-1980) focused on developing oral and transdermal sustained release systems and establishing controlled drug release mechanisms. The 2nd generation (1980-2010) was dedicated to the development of zero-order release systems, self-regulated drug delivery systems, long-term depot formulations, and nanotechnology-based delivery systems. The latter part of the 2nd generation was largely focused on studying nanoparticle formulations. The Journal of Controlled Release (JCR) has played a pivotal role in the 2nd generation of drug delivery technologies, and it will continue playing a leading role in the next generation. The best path towards a productive 3rd generation of drug delivery technology requires an honest, open dialog without any preconceived ideas of the past. The drug delivery field needs to take a bold approach to designing future drug delivery formulations primarily based on today's necessities, to produce the necessary innovations. The JCR provides a forum for sharing the new ideas that will shape the 3rd generation of drug delivery technology. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. 22 CFR 228.55 - Delivery services.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Delivery services. 228.55 Section 228.55 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT RULES ON SOURCE, ORIGIN AND NATIONALITY FOR COMMODITIES AND SERVICES FINANCED BY USAID Waivers § 228.55 Delivery services. (a) Ocean transportation. A...

  6. 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.

  7. Dendrimer Nanovectors for SiRNA Delivery.

    PubMed

    Liu, Xiaoxuan; Peng, Ling

    2016-01-01

    Small interfering RNA (SiRNA) delivery remains a major challenge in RNAi-based therapy. Dendrimers are emerging as appealing nonviral vectors for SiRNA delivery thanks to their well-defined architecture and their unique cooperativity and multivalency confined within a nanostructure. We have recently demonstrated that structurally flexible poly(amidoamine) (PAMAM) dendrimers are safe and effective nanovectors for SiRNA delivery in various disease models in vitro and in vivo. The present chapter showcases these dendrimers can package different SiRNA molecules into stable and nanosized particles, which protect SiRNA from degradation and promote cellular uptake of SiRNA, resulting in potent gene silencing at both mRNA and protein level in the prostate cancer cell model. Our results demonstrate this set of flexible PAMAM dendrimers are indeed safe and effective nonviral vectors for SiRNA delivery and hold great promise for further applications in functional genomics and RNAi-based therapies.

  8. Drug delivery technologies for autoimmune disease.

    PubMed

    Phillips, Brett E; Giannoukakis, Nick

    2010-11-01

    Targeting autoimmune disease poses two main challenges. The first is to identify unique targets to suppress directly or indirectly autoreactive cells exclusively. The second is to penetrate target tissues to deliver specifically drugs to desired cells that can achieve a therapeutic outcome. Herein, the range of drug delivery methods available and under development and how they can be useful to treat autoimmune diseases are discussed. Polymer delivery methods, as well as biological methods that include fusion proteins, targeted antibodies, recombinant viruses and cell products are compared. Readers will gain insight into the progression of clinical trials for different technologies and drug delivery methods useful for targeting and modulating the function of autoreactive immune cells. Several tissue-specific polymer-based and biologic drug delivery systems are now in Phase II/III clinical trials. Although these trials are focused mainly on cancer treatment, lessons from these trials can guide the use of the same agents for autoimmunity therapeutics.

  9. Multiscale benchmarking of drug delivery vectors.

    PubMed

    Summers, Huw D; Ware, Matthew J; Majithia, Ravish; Meissner, Kenith E; Godin, Biana; Rees, Paul

    2016-10-01

    Cross-system comparisons of drug delivery vectors are essential to ensure optimal design. An in-vitro experimental protocol is presented that separates the role of the delivery vector from that of its cargo in determining the cell response, thus allowing quantitative comparison of different systems. The technique is validated through benchmarking of the dose-response of human fibroblast cells exposed to the cationic molecule, polyethylene imine (PEI); delivered as a free molecule and as a cargo on the surface of CdSe nanoparticles and Silica microparticles. The exposure metrics are converted to a delivered dose with the transport properties of the different scale systems characterized by a delivery time, τ. The benchmarking highlights an agglomeration of the free PEI molecules into micron sized clusters and identifies the metric determining cell death as the total number of PEI molecules presented to cells, determined by the delivery vector dose and the surface density of the cargo. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Bioengineered Nanoparticles for siRNA delivery

    PubMed Central

    Kozielski, Kristen L.; Tzeng, Stephany Y.; Green, Jordan J.

    2014-01-01

    Short interfering RNA (siRNA) has been an important laboratory tool in the last two decades and has allowed researchers to better understand the functions of non-protein-coding genes through RNA interference (RNAi). Although RNAi holds great promise for this purpose as well as for treatment of many diseases, efforts at using siRNA have been hampered by the difficulty of safely and effectively introducing it into cells of interest, both in vitro and in vivo. To overcome this challenge, many biomaterials and nanoparticles (NPs) have been developed and optimized for siRNA delivery, often taking cues from the DNA delivery field, although different barriers exist for these two types of molecules. In this review, we discuss general properties of biomaterials and nanoparticles that are necessary for effective nucleic acid delivery. We also discuss specific examples of bioengineered materials, including lipid-based NPs, polymeric NPs, inorganic NPs, and RNA-based NPs, which clearly illustrate the problems and successes in siRNA delivery. PMID:23821336

  11. Intracarotid Delivery of Drugs: The Potential and the Pitfalls

    PubMed Central

    Joshi, Shailendra; Meyers, Phillip M.; Ornstein, Eugene

    2014-01-01

    The major efforts to selectively deliver drugs to the brain in the last decade have relied on smart molecular techniques to penetrate the blood brain barrier while intraarterial drug delivery has drawn relatively little attention. In the last decade there have been rapid advances in endovascular techniques. Modern endovascular procedures can permit highly targeted drug delivery by intracarotid route. Intracarotid drug delivery can be the primary route of drug delivery or it could be used to facilitate the delivery of smart-neuropharmaceuticals. There have been few attempts to systematically understand the kinetics of intracarotid drugs. Anecdotal data suggests that intracarotid drug delivery is effective in the treatment of cerebral vasospasm, thromboembolic strokes, and neoplasms. Neuroanesthesiologists are frequently involved in the care of such high-risk patients. Therefore, it is necessary to understand the applications of intracarotid drug delivery and the unusual kinetics of intracarotid drugs. PMID:18719453

  12. Project Delivery Methods.

    ERIC Educational Resources Information Center

    Dolan, Thomas G.

    2003-01-01

    Describes project delivery methods that are replacing the traditional Design/Bid/Build linear approach to the management, design, and construction of new facilities. These variations can enhance construction management and teamwork. (SLD)

  13. Recent advances of controlled drug delivery using microfluidic platforms.

    PubMed

    Sanjay, Sharma T; Zhou, Wan; Dou, Maowei; Tavakoli, Hamed; Ma, Lei; Xu, Feng; Li, XiuJun

    2018-03-15

    Conventional systematically-administered drugs distribute evenly throughout the body, get degraded and excreted rapidly while crossing many biological barriers, leaving minimum amounts of the drugs at pathological sites. Controlled drug delivery aims to deliver drugs to the target sites at desired rates and time, thus enhancing the drug efficacy, pharmacokinetics, and bioavailability while maintaining minimal side effects. Due to a number of unique advantages of the recent microfluidic lab-on-a-chip technology, microfluidic lab-on-a-chip has provided unprecedented opportunities for controlled drug delivery. Drugs can be efficiently delivered to the target sites at desired rates in a well-controlled manner by microfluidic platforms via integration, implantation, localization, automation, and precise control of various microdevice parameters. These features accordingly make reproducible, on-demand, and tunable drug delivery become feasible. On-demand self-tuning dynamic drug delivery systems have shown great potential for personalized drug delivery. This review presents an overview of recent advances in controlled drug delivery using microfluidic platforms. The review first briefly introduces microfabrication techniques of microfluidic platforms, followed by detailed descriptions of numerous microfluidic drug delivery systems that have significantly advanced the field of controlled drug delivery. Those microfluidic systems can be separated into four major categories, namely drug carrier-free micro-reservoir-based drug delivery systems, highly integrated carrier-free microfluidic lab-on-a-chip systems, drug carrier-integrated microfluidic systems, and microneedles. Microneedles can be further categorized into five different types, i.e. solid, porous, hollow, coated, and biodegradable microneedles, for controlled transdermal drug delivery. At the end, we discuss current limitations and future prospects of microfluidic platforms for controlled drug delivery. Copyright

  14. Impact of delivery mode on the colostrum microbiota composition.

    PubMed

    Toscano, Marco; De Grandi, Roberta; Peroni, Diego Giampietro; Grossi, Enzo; Facchin, Valentina; Comberiati, Pasquale; Drago, Lorenzo

    2017-09-25

    Breast milk is a rich nutrient with a temporally dynamic nature. In particular, numerous alterations in the nutritional, immunological and microbiological content occur during the transition from colostrum to mature milk. The objective of our study was to evaluate the potential impact of delivery mode on the microbiota of colostrum, at both the quantitative and qualitative levels (bacterial abundance and microbiota network). Twenty-nine Italian mothers (15 vaginal deliveries vs 14 Cesarean sections) were enrolled in the study. The microbiota of colostrum samples was analyzed by next generation sequencing (Ion Torrent Personal Genome Machine). The colostrum microbiota network associated with Cesarean section and vaginal delivery was evaluated by means of the Auto Contractive Map (AutoCM), a mathematical methodology based on Artificial Neural Network (ANN) architecture. Numerous differences between Cesarean section and vaginal delivery colostrum were observed. Vaginal delivery colostrum had a significant lower abundance of Pseudomonas spp., Staphylococcus spp. and Prevotella spp. when compared to Cesarean section colostrum samples. Furthermore, the mode of delivery had a strong influence on the microbiota network, as Cesarean section colostrum showed a higher number of bacterial hubs if compared to vaginal delivery, sharing only 5 hubs. Interestingly, the colostrum of mothers who had a Cesarean section was richer in environmental bacteria than mothers who underwent vaginal delivery. Finally, both Cesarean section and vaginal delivery colostrum contained a greater number of anaerobic bacteria genera. The mode of delivery had a large impact on the microbiota composition of colostrum. Further studies are needed to better define the meaning of the differences we observed between Cesarean section and vaginal delivery colostrum microbiota.

  15. Negotiating the Digital Library: Document Delivery.

    ERIC Educational Resources Information Center

    Jacobs, Neil; Morris, Anne

    1999-01-01

    The eLib-funded FIDDO (Focused Investigation of Document Delivery Options) project provides library managers/others with information to support policy decisions. Senior libraries were interviewed about the future of document delivery and interviews were analyzed with the support of NUD*IST (Nonnumerical Unstructured Data by Indexing, Searching and…

  16. Development of controlled drug delivery systems for bone fracture-targeted therapeutic delivery: A review.

    PubMed

    Wang, Yuchen; Newman, Maureen R; Benoit, Danielle S W

    2018-06-01

    Impaired fracture healing is a major clinical problem that can lead to patient disability, prolonged hospitalization, and significant financial burden. Although the majority of fractures heal using standard clinical practices, approximately 10% suffer from delayed unions or non-unions. A wide range of factors contribute to the risk for nonunions including internal factors, such as patient age, gender, and comorbidities, and external factors, such as the location and extent of injury. Current clinical approaches to treat nonunions include bone grafts and low-intensity pulsed ultrasound (LIPUS), which realizes clinical success only to select patients due to limitations including donor morbidities (grafts) and necessity of fracture reduction (LIPUS), respectively. To date, therapeutic approaches for bone regeneration rely heavily on protein-based growth factors such as INFUSE, an FDA-approved scaffold for delivery of bone morphogenetic protein 2 (BMP-2). Small molecule modulators and RNAi therapeutics are under development to circumvent challenges associated with traditional growth factors. While preclinical studies has shown promise, drug delivery has become a major hurdle stalling clinical translation. Therefore, this review overviews current therapies employed to stimulate fracture healing pre-clinically and clinically, including a focus on drug delivery systems for growth factors, parathyroid hormone (PTH), small molecules, and RNAi therapeutics, as well as recent advances and future promise of fracture-targeted drug delivery. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. 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

  18. Microneedles: quick and easy delivery methods of vaccines

    PubMed Central

    2017-01-01

    Vaccination is the most efficient method for infectious disease prevention. Parenteral injections such as intramuscular, intradermal, and subcutaneous injections have several advantages in vaccine delivery, but there are many drawbacks. Thus, the development of a new vaccine delivery system has long been required. Recently, microneedles have been attracting attention as new vaccination tools. Microneedle is a highly effective transdermal vaccine delivery method due to its mechanism of action, painlessness, and ease of use. Here, we summarized the characteristics of microneedles and the possibilities as a new vaccine delivery route. PMID:28775980

  19. Silk-based delivery systems of bioactive molecules

    PubMed Central

    Numata, Keiji; Kaplan, David L

    2010-01-01

    Silks are biodegradable, biocompatible, self-assemblying proteins that can also be tailored via genetic engineering to contain specific chemical features, offering utility for drug and gene delivery. Silkworm silk has been used in biomedical sutures for decades and has recently achieved Food and Drug Administration approval for expanded biomaterials device utility. With the diversity and control of size, structure and chemistry, modified or recombinant silk proteins can be designed and utilized in various biomedical application, such as for the delivery of bioactive molecules. This review focuses on the biosynthesis and applications of silk-based multi-block copolymer systems and related silk protein drug delivery systems. The utility of these systems for the delivery of small molecule drugs, proteins and genes are reviewed. PMID:20298729

  20. Controlling subcellular delivery to optimize therapeutic effect

    PubMed Central

    Mossalam, Mohanad; Dixon, Andrew S; Lim, Carol S

    2010-01-01

    This article focuses on drug targeting to specific cellular organelles for therapeutic purposes. Drugs can be delivered to all major organelles of the cell (cytosol, endosome/lysosome, nucleus, nucleolus, mitochondria, endoplasmic reticulum, Golgi apparatus, peroxisomes and proteasomes) where they exert specific effects in those particular subcellular compartments. Delivery can be achieved by chemical (e.g., polymeric) or biological (e.g., signal sequences) means. Unidirectional targeting to individual organelles has proven to be immensely successful for drug therapy. Newer technologies that accommodate multiple signals (e.g., protein switch and virus-like delivery systems) mimic nature and allow for a more sophisticated approach to drug delivery. Harnessing different methods of targeting multiple organelles in a cell will lead to better drug delivery and improvements in disease therapy. PMID:21113240

  1. Micro-scale Devices for Transdermal Drug Delivery

    PubMed Central

    Arora, Anubhav; Prausnitz, Mark; Mitragotri, Samir

    2009-01-01

    Skin makes an excellent site for drug and vaccine delivery due to easy accessibility, immuno-surveillance functions, avoidance of macromolecular degradation in the gastrointestinal tract and possibility of self-administration. However, macromolecular drug delivery across the skin is primarily accomplished using hypodermic needles, which have several disadvantages including accidental needle-sticks, pain and needle phobia. These limitations have led to extensive research and development of alternative methods for drug and vaccine delivery across the skin. This review focuses on the recent trends and developments in this field of micro-scale devices for transdermal macromolecular delivery. These include liquid jet injectors, powder injectors, microneedles and thermal microablation. The historical perspective, mechanisms of action, important design parameters, applications and challenges are discussed for each method. PMID:18805472

  2. Variability in Nose-to-Lung Aerosol Delivery

    PubMed Central

    Walenga, Ross L; Tian, Geng; Hindle, Michael; Yelverton, Joshua; Dodson, Kelley; Longest, P. Worth

    2014-01-01

    Nasal delivery of lung targeted pharmaceutical aerosols is ideal for drugs that need to be administered during high flow nasal cannula (HFNC) gas delivery, but based on previous studies losses and variability through both the delivery system and nasal cavity are expected to be high. The objective of this study was to assess the variability in aerosol delivery through the nose to the lungs with a nasal cannula interface for conventional and excipient enhanced growth (EEG) delivery techniques. A database of nasal cavity computed tomography (CT) scans was collected and analyzed, from which four models were selected to represent a wide range of adult anatomies, quantified based on the nasal surface area-to-volume ratio (SA/V). Computational fluid dynamics (CFD) methods were validated with existing in vitro data and used to predict aerosol delivery through a streamlined nasal cannula and the four nasal models at a steady state flow rate of 30 L/min. Aerosols considered were solid particles for EEG delivery (initial 0.9 μm and 1.5 μm aerodynamic diameters) and conventional droplets (5 μm) for a control case. Use of the EEG approach was found to reduce depositional losses in the nasal cavity by an order of magnitude and substantially reduce variability. Specifically, for aerosol deposition efficiency in the four geometries, the 95% confidence intervals (CI) for 0.9 and 5 μm aerosols were 2.3-3.1 and 15.5-66.3%, respectively. Simulations showed that the use of EEG as opposed to conventional methods improved delivered dose of aerosols through the nasopharynx, expressed as penetration fraction (PF), by approximately a factor of four. Variability of PF, expressed by the coefficient of variation (CV), was reduced by a factor of four with EEG delivery compared with the control case. Penetration fraction correlated well with SA/V for larger aerosols, but smaller aerosols showed some dependence on nasopharyngeal exit hydraulic diameter. In conclusion, results indicated that

  3. SU-F-T-459: ArcCHECK Machine QA : Highly Efficient Quality Assurance Tool for VMAT, SRS & SBRT Linear Accelerator Delivery

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

    Mhatre, V; Patwe, P; Dandekar, P

    Purpose: Quality assurance (QA) of complex linear accelerators is critical and highly time consuming. ArcCHECK Machine QA tool is used to test geometric and delivery aspects of linear accelerator. In this study we evaluated the performance of this tool. Methods: Machine QA feature allows user to perform quality assurance tests using ArcCHECK phantom. Following tests were performed 1) Gantry Speed 2) Gantry Rotation 3) Gantry Angle 4)MLC/Collimator QA 5)Beam Profile Flatness & Symmetry. Data was collected on trueBEAM stX machine for 6 MV for a period of one year. The Gantry QA test allows to view errors in gantry angle,more » rotation & assess how accurately the gantry moves around the isocentre. The MLC/Collimator QA tool is used to analyze & locate the differences between leaf bank & jaw position of linac. The flatness & Symmetry test quantifies beam flatness & symmetry in IEC-y & x direction. The Gantry & Flatness/Symmetry test can be performed for static & dynamic delivery. Results: The Gantry speed was 3.9 deg/sec with speed maximum deviation around 0.3 deg/sec. The Gantry Isocentre for arc delivery was 0.9mm & static delivery was 0.4mm. The maximum percent positive & negative difference was found to be 1.9 % & – 0.25 % & maximum distance positive & negative diff was 0.4mm & – 0.3 mm for MLC/Collimator QA. The Flatness for Arc delivery was 1.8 % & Symmetry for Y was 0.8 % & X was 1.8 %. The Flatness for gantry 0°,270°,90° & 180° was 1.75,1.9,1.8 & 1.6% respectively & Symmetry for X & Y was 0.8,0.6% for 0°, 0.6,0.7% for 270°, 0.6,1% for 90° & 0.6,0.7% for 180°. Conclusion: ArcCHECK Machine QA is an useful tool for QA of Modern linear accelerators as it tests both geometric & delivery aspects. This is very important for VMAT, SRS & SBRT treatments.« less

  4. Nanocrystal for ocular drug delivery: hope or hype.

    PubMed

    Sharma, Om Prakash; Patel, Viral; Mehta, Tejal

    2016-08-01

    The complexity of the structure and nature of the eye emanates a challenge for drug delivery to formulation scientists. Lower bioavailability concern of conventional ocular formulation provokes the interest of researchers in the development of novel drug delivery system. Nanotechnology-based formulations have been extensively investigated and found propitious in improving bioavailability of drugs by overcoming ocular barriers prevailing in the eye. The advent of nanocrystals helped in combating the problem of poorly soluble drugs specifically for oral and parenteral drug delivery and led to development of various marketed products. Nanocrystal-based formulations explored for ocular drug delivery have been found successful in achieving increase in retention time, bioavailability, and permeability of drugs across the corneal and conjunctival epithelium. In this review, we have highlighted the ocular physiology and barriers in drug delivery. A comparative analysis of various nanotechnology-based ocular formulations is done with their pros and cons. Consideration is also given to various methods of preparation of nanocrystals with their patented technology. This article highlights the success achieved in conquering various challenges of ocular delivery by the use of nanocrystals while emphasizing on its advantages and application for ocular formulation. The perspectives of nanocrystals as an emerging flipside to explore the frontiers of ocular drug delivery are discussed.

  5. 25 CFR 135.23 - Refusal of water delivery.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Refusal of water delivery. 135.23 Section 135.23 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR FINANCIAL ACTIVITIES CONSTRUCTION ASSESSMENTS, CROW... District § 135.23 Refusal of water delivery. The right is reserved to refuse the delivery of water to any...

  6. 48 CFR 552.211-80 - Age on Delivery.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false Age on Delivery. 552.211... AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 552.211-80 Age on Delivery. As prescribed in 511.404(a)(2) insert the following clause: Age on Delivery (FEB 1996...

  7. 48 CFR 552.211-80 - Age on Delivery.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false Age on Delivery. 552.211... AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 552.211-80 Age on Delivery. As prescribed in 511.404(a)(2) insert the following clause: Age on Delivery (FEB 1996...

  8. 48 CFR 552.211-80 - Age on Delivery.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Age on Delivery. 552.211... AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 552.211-80 Age on Delivery. As prescribed in 511.404(a)(2) insert the following clause: Age on Delivery (FEB 1996...

  9. 48 CFR 552.211-80 - Age on Delivery.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false Age on Delivery. 552.211... AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 552.211-80 Age on Delivery. As prescribed in 511.404(a)(2) insert the following clause: Age on Delivery (FEB 1996...

  10. 48 CFR 552.211-80 - Age on Delivery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Age on Delivery. 552.211... AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 552.211-80 Age on Delivery. As prescribed in 511.404(a)(2) insert the following clause: Age on Delivery (FEB 1996...

  11. 25 CFR 135.23 - Refusal of water delivery.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Refusal of water delivery. 135.23 Section 135.23 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR FINANCIAL ACTIVITIES CONSTRUCTION ASSESSMENTS, CROW... District § 135.23 Refusal of water delivery. The right is reserved to refuse the delivery of water to any...

  12. 25 CFR 135.23 - Refusal of water delivery.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true Refusal of water delivery. 135.23 Section 135.23 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR FINANCIAL ACTIVITIES CONSTRUCTION ASSESSMENTS, CROW... District § 135.23 Refusal of water delivery. The right is reserved to refuse the delivery of water to any...

  13. 25 CFR 135.23 - Refusal of water delivery.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Refusal of water delivery. 135.23 Section 135.23 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR FINANCIAL ACTIVITIES CONSTRUCTION ASSESSMENTS, CROW... District § 135.23 Refusal of water delivery. The right is reserved to refuse the delivery of water to any...

  14. Enhancing endosomal escape for nanoparticle mediated siRNA delivery

    NASA Astrophysics Data System (ADS)

    Ma, Da

    2014-05-01

    Gene therapy with siRNA is a promising biotechnology to treat cancer and other diseases. To realize siRNA-based gene therapy, a safe and efficient delivery method is essential. Nanoparticle mediated siRNA delivery is of great importance to overcome biological barriers for systemic delivery in vivo. Based on recent discoveries, endosomal escape is a critical biological barrier to be overcome for siRNA delivery. This feature article focuses on endosomal escape strategies used for nanoparticle mediated siRNA delivery, including cationic polymers, pH sensitive polymers, calcium phosphate, and cell penetrating peptides. Work has been done to develop different endosomal escape strategies based on nanoparticle types, administration routes, and target organ/cell types. Also, enhancement of endosomal escape has been considered along with other aspects of siRNA delivery to ensure target specific accumulation, high cell uptake, and low toxicity. By enhancing endosomal escape and overcoming other biological barriers, great progress has been achieved in nanoparticle mediated siRNA delivery.

  15. Composite nanoparticles for gene delivery.

    PubMed

    Wang, Yuhua; Huang, Leaf

    2014-01-01

    Nanoparticle-mediated gene and siRNA delivery has been an appealing area to gene therapists when they attempt to treat the diseases by manipulating the genetic information in the target cells. However, the advances in materials science could not keep up with the demand for multifunctional nanomaterials to achieve desired delivery efficiency. Researchers have thus taken an alternative approach to incorporate various materials into single composite nanoparticle using different fabrication methods. This approach allows nanoparticles to possess defined nanostructures as well as multiple functionalities to overcome the critical extracellular and intracellular barriers to successful gene delivery. This chapter will highlight the advances of fabrication methods that have the most potential to translate nanoparticles from bench to bedside. Furthermore, a major class of composite nanoparticle-lipid-based composite nanoparticles will be classified based on the components and reviewed in details.

  16. Calcium phosphate ceramics in drug delivery

    NASA Astrophysics Data System (ADS)

    Bose, Susmita; Tarafder, Solaiman; Edgington, Joe; Bandyopadhyay, Amit

    2011-04-01

    Calcium phosphate (CaP) particulates, cements and scaffolds have attracted significant interest as drug delivery vehicles. CaP systems, including both hydroxyapaptite and tricalcium phosphates, possess variable stoichiometry, functionality and dissolution properties which make them suitable for cellular delivery. Their chemical similarity to bone and thus biocompatibility, as well as variable surface charge density contribute to their controlled release properties. Among specific research areas, nanoparticle size, morphology, surface area due to porosity, and chemistry controlled release kinetics are the most active. This article discusses CaP systems in their particulate, cements, and scaffold forms for drug, protein, and growth factor delivery toward orthopedic and dental applications.

  17. Bioengineering approaches to controlled protein delivery.

    PubMed

    Kobsa, Serge; Saltzman, W Mark

    2008-05-01

    Proteins are of crucial importance in all biologic organisms, in terms of both structure and function. Their deficits play central roles in many pathologic states, and their potential as powerful therapeutic agents has been widely recognized. Many issues, however, exist in delivery of biologically active proteins to target tissues and organs. Recent advances in biomedical engineering have lead to development of advanced techniques for controlled delivery of peptides and proteins, paving the way for their efficient use in treating human injury and disease. With a particular emphasis on most recent advances, this review discusses currently available techniques for controlled delivery of proteins and considers future research directions.

  18. Twin vaginal delivery: innovate or abdicate.

    PubMed

    Easter, Sarah Rae; Taouk, Laura; Schulkin, Jay; Robinson, Julian N

    2017-05-01

    Neonatal safety data along with national guidelines have prompted renewed interest in vaginal delivery of twins, particularly in the case of the noncephalic second twin. Yet, the rising rate of twin cesarean deliveries, coupled with the national decline in operative obstetrics, raises concerns about the availability of providers who are skilled in twin vaginal birth. Providers are key stakeholders for increasing rates of twin vaginal delivery. We surveyed a group of practicing obstetricians to explore potential barriers to the vaginal birth of twins with a focus on delivery of the noncephalic second twin. Among 107 responding providers, only 57% would deliver a noncephalic second twin by breech extraction. Providers who preferred breech extraction had a higher rate of maternal-fetal medicine subspecialty training (26.2% vs 4.3%; P<.01) and were more likely to be in an academic practice environment (36.1% vs 10.9%; P<.01) and to practice in high-volume centers that deliver >30 sets of twins annually (57.4% vs 34.8%; P=.02). Most providers (54.2%) were familiar with the findings from the recent randomized trial that demonstrated the safety of twin vaginal birth. However, knowledge of the trial was not associated statistically with a preference for breech extraction (62.3% vs 43.5%; P=.05). Providers who preferred breech extraction were more likely to agree with recent society guidelines that encourage the vaginal birth of twins (86.9% vs 63.0%; P<.01). In an adjusted analysis, the 46% of providers with a perceived need for more training were far less likely to prefer breech extraction for delivery of a noncephalic second twin (adjusted odds ratio, 0.38; 95% confidence interval, 0.16-0.95). Furthermore, 57% of providers who would not offer their patient breech extraction would be willing to consult a colleague for support with a noncephalic twin delivery. These results suggest that scientific evidence and society opinion are likely insufficient to reverse the national

  19. Health Service Delivery in Developing Countries

    ERIC Educational Resources Information Center

    Benyoussef, Amor

    1977-01-01

    Reviews recent work dealing with methodological and technical issues in health and development; presents examples of the application of social sciences, including health demography and economics, in questions of health services delivery; and analyzes delivery of health services to rural and nomadic populations in Africa, Asia, and Latin America.…

  20. Information Delivery Options over Three Decades.

    ERIC Educational Resources Information Center

    Kennedy, H. Edward

    1986-01-01

    The rate of new technology-driven innovations for information delivery has accelerated over the past three decades. New information delivery formats in the 1950s and 1960s included microforms and, in response to demands from librarians, indexing and abstracting services began to make their publications available on this medium. Electronic…

  1. Micro injector sample delivery system for charged molecules

    DOEpatents

    Davidson, James C.; Balch, Joseph W.

    1999-11-09

    A micro injector sample delivery system for charged molecules. The injector is used for collecting and delivering controlled amounts of charged molecule samples for subsequent analysis. The injector delivery system can be scaled to large numbers (>96) for sample delivery to massively parallel high throughput analysis systems. The essence of the injector system is an electric field controllable loading tip including a section of porous material. By applying the appropriate polarity bias potential to the injector tip, charged molecules will migrate into porous material, and by reversing the polarity bias potential the molecules are ejected or forced away from the tip. The invention has application for uptake of charged biological molecules (e.g. proteins, nucleic acids, polymers, etc.) for delivery to analytical systems, and can be used in automated sample delivery systems.

  2. Accurate mass measurement: terminology and treatment of data.

    PubMed

    Brenton, A Gareth; Godfrey, A Ruth

    2010-11-01

    High-resolution mass spectrometry has become ever more accessible with improvements in instrumentation, such as modern FT-ICR and Orbitrap mass spectrometers. This has resulted in an increase in the number of articles submitted for publication quoting accurate mass data. There is a plethora of terms related to accurate mass analysis that are in current usage, many employed incorrectly or inconsistently. This article is based on a set of notes prepared by the authors for research students and staff in our laboratories as a guide to the correct terminology and basic statistical procedures to apply in relation to mass measurement, particularly for accurate mass measurement. It elaborates on the editorial by Gross in 1994 regarding the use of accurate masses for structure confirmation. We have presented and defined the main terms in use with reference to the International Union of Pure and Applied Chemistry (IUPAC) recommendations for nomenclature and symbolism for mass spectrometry. The correct use of statistics and treatment of data is illustrated as a guide to new and existing mass spectrometry users with a series of examples as well as statistical methods to compare different experimental methods and datasets. Copyright © 2010. Published by Elsevier Inc.

  3. Porous Inorganic Drug Delivery Systems-a Review.

    PubMed

    Sayed, E; Haj-Ahmad, R; Ruparelia, K; Arshad, M S; Chang, M-W; Ahmad, Z

    2017-07-01

    Innovative methods and materials have been developed to overcome limitations associated with current drug delivery systems. Significant developments have led to the use of a variety of materials (as excipients) such as inorganic and metallic structures, marking a transition from conventional polymers. Inorganic materials, especially those possessing significant porosity, are emerging as good candidates for the delivery of a range of drugs (antibiotics, anticancer and anti-inflammatories), providing several advantages in formulation and engineering (encapsulation of drug in amorphous form, controlled delivery and improved targeting). This review focuses on key selected developments in porous drug delivery systems. The review provides a short broad overview of porous polymeric materials for drug delivery before focusing on porous inorganic materials (e.g. Santa Barbara Amorphous (SBA) and Mobil Composition of Matter (MCM)) and their utilisation in drug dosage form development. Methods for their preparation and drug loading thereafter are detailed. Several examples of porous inorganic materials, drugs used and outcomes are discussed providing the reader with an understanding of advances in the field and realistic opportunities.

  4. 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

  5. Biopolymers as transdermal drug delivery systems in dermatology therapy.

    PubMed

    Basavaraj, K H; Johnsy, George; Navya, M A; Rashmi, R; Siddaramaiah

    2010-01-01

    The skin is considered a complex organ for drug delivery because of its structure. Drug delivery systems are designed for the controlled release of drugs through the skin into the systemic circulation, maintaining consistent efficacy and reducing the dose of the drugs and their related side effects. Transdermal drug delivery represents one of the most rapidly advancing areas of novel drug delivery. The excellent impervious nature of the skin is the greatest challenge that must be overcome for successful drug delivery. Today, polymers have been proven to be successful for long-term drug delivery applications as no single polymer can satisfy all of the requirements. Biopolymers in the field of dermal application are rare and the mechanisms that affect skin absorption are almost unknown. Biopolymers are widely used as drug delivery systems, but as such the use of biopolymers as drug delivery systems in dermatologic therapy is still in progress. Commonly used biopolymers include hydrocolloids, alginates, hydrogels, polyurethane, collagen, poly(lactic-co-glycolic acid), chitosan, proteins and peptides, pectin, siRNAs, and hyaluronic acid. These new and exciting methods for drug delivery are already increasing the number and quality of dermal and transdermal therapies. This article reviews current research on biopolymers and focuses on their potential as drug carriers, particularly in relation to the dermatologic aspects of their use.

  6. 25 CFR 135.6 - Refusal of water delivery.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Refusal of water delivery. 135.6 Section 135.6 Indians... INDIAN IRRIGATION PROJECT Charges Assessed Against Irrigation District Lands § 135.6 Refusal of water delivery. The right is reserved to the United States to refuse the delivery of water to each of the said...

  7. 25 CFR 135.6 - Refusal of water delivery.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Refusal of water delivery. 135.6 Section 135.6 Indians... INDIAN IRRIGATION PROJECT Charges Assessed Against Irrigation District Lands § 135.6 Refusal of water delivery. The right is reserved to the United States to refuse the delivery of water to each of the said...

  8. 25 CFR 135.6 - Refusal of water delivery.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true Refusal of water delivery. 135.6 Section 135.6 Indians... INDIAN IRRIGATION PROJECT Charges Assessed Against Irrigation District Lands § 135.6 Refusal of water delivery. The right is reserved to the United States to refuse the delivery of water to each of the said...

  9. 25 CFR 135.6 - Refusal of water delivery.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Refusal of water delivery. 135.6 Section 135.6 Indians... INDIAN IRRIGATION PROJECT Charges Assessed Against Irrigation District Lands § 135.6 Refusal of water delivery. The right is reserved to the United States to refuse the delivery of water to each of the said...

  10. 4D laser camera for accurate patient positioning, collision avoidance, image fusion and adaptive approaches during diagnostic and therapeutic procedures.

    PubMed

    Brahme, Anders; Nyman, Peter; Skatt, Björn

    2008-05-01

    A four-dimensional (4D) laser camera (LC) has been developed for accurate patient imaging in diagnostic and therapeutic radiology. A complementary metal-oxide semiconductor camera images the intersection of a scanned fan shaped laser beam with the surface of the patient and allows real time recording of movements in a three-dimensional (3D) or four-dimensional (4D) format (3D +time). The LC system was first designed as an accurate patient setup tool during diagnostic and therapeutic applications but was found to be of much wider applicability as a general 4D photon "tag" for the surface of the patient in different clinical procedures. It is presently used as a 3D or 4D optical benchmark or tag for accurate delineation of the patient surface as demonstrated for patient auto setup, breathing and heart motion detection. Furthermore, its future potential applications in gating, adaptive therapy, 3D or 4D image fusion between most imaging modalities and image processing are discussed. It is shown that the LC system has a geometrical resolution of about 0, 1 mm and that the rigid body repositioning accuracy is about 0, 5 mm below 20 mm displacements, 1 mm below 40 mm and better than 2 mm at 70 mm. This indicates a slight need for repeated repositioning when the initial error is larger than about 50 mm. The positioning accuracy with standard patient setup procedures for prostate cancer at Karolinska was found to be about 5-6 mm when independently measured using the LC system. The system was found valuable for positron emission tomography-computed tomography (PET-CT) in vivo tumor and dose delivery imaging where it potentially may allow effective correction for breathing artifacts in 4D PET-CT and image fusion with lymph node atlases for accurate target volume definition in oncology. With a LC system in all imaging and radiation therapy rooms, auto setup during repeated diagnostic and therapeutic procedures may save around 5 min per session, increase accuracy and allow

  11. Getting to Grips with Online Delivery.

    ERIC Educational Resources Information Center

    Booker, Di

    This booklet, which is intended for general readers wishing to understand important trends in vocational education and training (VET) in Australia, provides an overview of the basic issues in online delivery of VET. The following topics are discussed in the booklet's first six sections: (1) basic principles of online delivery; (2) benefits and…

  12. Distance Synchronous Information Systems Course Delivery

    ERIC Educational Resources Information Center

    Peslak, Alan R.; Lewis, Griffith R.; Aebli, Fred

    2014-01-01

    Teaching computer information systems via distance education is a challenge for both student and faculty. Much research work has been performed on methods of teaching via distance education. Today we are faced with a variety of options for course delivery. Asynchronous delivery via online or lesson instruction still remains most common. But…

  13. Recent developments in solid lipid nanoparticle and surface-modified solid lipid nanoparticle delivery systems for oral delivery of phyto-bioactive compounds in various chronic diseases

    PubMed Central

    Ko, Young Tag; Choi, Dong-Kug

    2018-01-01

    Solid lipid nanoparticle (SLN) delivery systems have a wide applicability in the delivery of phyto-bioactive compounds to treat various chronic diseases, including diabetes, cancer, obesity and neurodegenerative diseases. The multiple benefits of SLN delivery include improved stability, smaller particle size, leaching prevention and enhanced lymphatic uptake of the bioactive compounds through oral delivery. However, the burst release makes the SLN delivery systems inadequate for the oral delivery of various phyto-bioactive compounds that can treat such chronic diseases. Recently, the surface-modified SLN (SMSLN) was observed to overcome this limitation for oral delivery of phyto-bioactive compounds, and there is growing evidence of an enhanced uptake of curcumin delivered orally via SMSLNs in the brain. This review focuses on different SLN and SMSLN systems that are useful for oral delivery of phyto-bioactive compounds to treat various chronic diseases. PMID:29588585

  14. Continuous intraputamenal convection-enhanced delivery in adult rhesus macaques.

    PubMed

    Fan, Xiaotong; Nelson, Brian D; Ai, Yi; Stiles, David K; Gash, Don M; Hardy, Peter A; Zhang, Zhiming

    2015-12-01

    Assessing the safety and feasibility of chronic delivery of compounds to the brain using convection-enhanced delivery (CED) is important for the further development of this important therapeutic technology. The objective of this study was to follow and model the distribution of a compound delivered by CED into the putamen of rhesus monkeys. The authors sequentially implanted catheters into 4 sites spanning the left and right putamen in each of 6 rhesus monkeys. The catheters were connected to implanted pumps, which were programmed to deliver a 5-mM solution of the MRI contrast agent Gd-DTPA at 0.1 μl/minute for 7 days and 0.3 μl/minute for an additional 7 days. The animals were followed for 28 days per implant cycle during which they were periodically examined with MRI. All animals survived the 4 surgeries with no deficits in behavior. Compared with acute infusion, the volume of distribution (Vd) increased 2-fold with 7 days of chronic infusion. Increasing the flow rate 3-fold over the next week increased the Vd an additional 3-fold. Following withdrawal of the compound, the half-life of Gd-DTPA in the brain was estimated as 3.1 days based on first-order pharmacokinetics. Histological assessment of the brain showed minimal tissue damage limited to the insertion site. These results demonstrate several important features in the development of a chronically implanted pump and catheter system: 1) the ability to place catheters accurately in a predetermined target; 2) the ability to deliver compounds in a chronic fashion to the putamen; and 3) the use of MRI and MR visible tracers to follow the evolution of the infusion volume over time.

  15. Silk-based delivery systems of bioactive molecules.

    PubMed

    Numata, Keiji; Kaplan, David L

    2010-12-30

    Silks are biodegradable, biocompatible, self-assembling proteins that can also be tailored via genetic engineering to contain specific chemical features, offering utility for drug and gene delivery. Silkworm silk has been used in biomedical sutures for decades and has recently achieved Food and Drug Administration approval for expanded biomaterials device utility. With the diversity and control of size, structure and chemistry, modified or recombinant silk proteins can be designed and utilized in various biomedical application, such as for the delivery of bioactive molecules. This review focuses on the biosynthesis and applications of silk-based multi-block copolymer systems and related silk protein drug delivery systems. The utility of these systems for the delivery of small molecule drugs, proteins and genes is reviewed. Copyright © 2010 Elsevier B.V. All rights reserved.

  16. Multi-Sided Markets for Transforming Healthcare Service Delivery.

    PubMed

    Kuziemsky, Craig; Vimarlund, Vivian

    2018-01-01

    Changes in healthcare delivery needs have necessitated the design of new models for connecting providers and consumers of services. While healthcare delivery has traditionally been a push market, multi-sided markets offer the potential for transitioning to a pull market for service delivery. However, there is a need to better understand the business model for multi-sided markets as a first step to using them in healthcare. This paper addressed that need and describes a multi-sided market evaluation framework. Our framework identifies patient, governance and service delivery as three levels of brokerage consideration for evaluating multi-sided markets in healthcare.

  17. Fetal presentation and successful twin vaginal delivery.

    PubMed

    Easter, Sarah Rae; Lieberman, Ellice; Carusi, Daniela

    2016-01-01

    Despite the demonstrated safety of a trial of labor for pregnancies with a vertex-presenting twin and clinical guidelines in support of this plan, the rate of planned cesarean delivery for twin pregnancies remains high. This high rate, as well as variation in cesarean rates for twin pregnancies across providers, may be influenced strongly by concern about delivery of the second twin, particularly when it is in a nonvertex presentation. There are limited data in the literature that has examined the impact of the position of the nonpresenting twin on successful vaginal delivery or maternal/neonatal morbidity. We hypothesized that nonvertex presentation of the second twin would be associated with lower rates of successful vaginal birth for those patients attempting labor. This institutional review board-approved, retrospective cohort study of women who labored with twin pregnancies in a single urban hospital from 2007-2011. We included women with vertex-presenting first twins at >32 weeks gestation without a contraindication to labor and excluded those with uterine scar or lethal fetal anomaly. Vaginal delivery rates were evaluated according to vertex or nonvertex presentation of the second twin at admission and again at delivery. Maternal and neonatal morbidities were evaluated separately. Logistic regression was used to control for multiple confounders. Seven hundred sixteen patients met the inclusion criteria; 349 patients (49%) underwent a trial of labor. This included 73% (296/406) of eligible vertex/vertex twins and 17% (53/310) eligible vertex/nonvertex twins (P < .01). When compared with laboring patients with vertex/vertex-presenting twins, those with vertex/nonvertex twins were younger (median age, 32 vs 33 years; P = .05), were more often multiparous (60% vs 43%; P = .02), and were less likely to have hypertension (13% vs 27%; P = .03). Eighty-five percent of patients with nonvertex second twins at admission delivered vaginally, compared with 70% of

  18. Ultrasound mediated nanoparticle drug delivery

    NASA Astrophysics Data System (ADS)

    Mullin, Lee B.

    Ultrasound is not only a powerful diagnostic tool, but also a promising therapeutic technology that can be used to improve localized drug delivery. Microbubble contrast agents are micron sized encapsulated gas filled bubbles that are administered intravenously. Originally developed to enhance ultrasound images, microbubbles are highly echogenic due to the gas core that provides a detectable impedance difference from the surrounding medium. The core also allows for controlled response of the microbubbles to ultrasound pulses. Microbubbles can be pushed using acoustic radiation force and ruptured using high pressures. Destruction of microbubbles can increase permeability at the cellular and vascular level, which can be advantageous for drug delivery. Advances in drug delivery methods have been seen with the introduction of nanoparticles, nanometer sized objects often carrying a drug payload. In chemotherapy, nanoparticles can deliver drugs to tumors while limiting systemic exposure due to abnormalities in tumor vasculature such large gaps between endothelial cells that allow nanoparticles to enter into the interstitial space; this is referred to as the enhanced permeability and retention (EPR) effect. However, this effect may be overestimated in many tumors. Additionally, only a small percentage of the injected dose accumulates in the tumor, which most the nanoparticles accumulating in the liver and spleen. It is hypothesized that combining the acoustic activity of an ultrasound contrast agent with the high payload and extravasation ability of a nanoparticle, localized delivery to the tumor with reduced systemic toxicity can be achieved. This method can be accomplished by either loading nanoparticles onto the shell of the microbubble or through a coadministration method of both nanoparticles and microbubbles. The work presented in this dissertation utilizes novel and commercial nanoparticle formulations, combined with microbubbles and a variety of ultrasound systems

  19. A review of implantable biosensors for closed-loop glucose control and other drug delivery applications.

    PubMed

    Scholten, Kee; Meng, Ellis

    2018-06-15

    Closed-loop drug delivery promises autonomous control of pharmacotherapy through the continuous monitoring of biomarker levels. For decades, researchers have strived for portable closed-loop systems capable of treating ambulatory patients with chronic conditions such as diabetes mellitus. After years of development, the first of these systems have left the laboratory and entered commercial use. This long-awaited advance reflects recent development of chronically stable implantable biosensors able to accurately measure biomarker levels in vivo. This review discusses the role of implantable biosensors in closed-loop drug delivery applications, with the intent to provide a resource for engineers and researchers studying such systems. We provide an overview of common biosensor designs and review the principle challenges in implementing long indwelling sensors: namely device sensitivity, selectivity, and lifetime. This review examines novel advances in transducer design, biological interface, and material biocompatibility, with a focus on recent academic and commercial work which provide successful strategies to overcome perennial challenges. This review focuses primarily on the topics of closed-loop glucose control and continuous glucose monitoring biosensors, which make up the overwhelming majority of published research in this area. We conclude with an overview of recent advances in closed-loop systems targeting applications outside blood glucose management. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. A novel pen-based Bluetooth-enabled insulin delivery system with insulin dose tracking and advice.

    PubMed

    Bailey, Timothy S; Stone, Jenine Y

    2017-05-01

    Diabetes is growing in prevalence internationally. As more individuals require insulin as part of their treatment, technology evolves to optimize delivery, improve adherence, and reduce dosing errors. Insulin pens outperform vial and syringe in simplicity, dosing accuracy, and user preference. Bolus advisors improve dosing confidence and treatment adherence. The InPen System offers a novel approach to treatment via a wireless pen that syncs to a mobile application featuring a bolus advisor, enabling convenient insulin dose tracking and more accurate bolus advice among other features. Areas covered: Existing technology for insulin delivery and bolus advice are reviewed. The mechanics and functionality of the InPen device are delineated. Findings from formative testing and usability studies of the InPen system are reported. Future directions for the InPen system in the treatment of diabetes are discussed. Expert opinion: Diabetes management is complex and largely data-driven. The InPen System offers a promising new opportunity to avail insulin pen-users of features known to improve treatment efficacy, which have otherwise primarily been available to those using pumps. Given that the majority of insulin users do not use insulin pumps, the InPen System is poised to improve glucose control in a significant portion of the diabetes population.

  1. Drug delivery with microsecond laser pulses into gelatin.

    PubMed

    Shangguan, H; Casperson, L W; Shearin, A; Gregory, K W; Prahl, S A

    1996-07-01

    Photo acoustic drug delivery is a technique for localized drug delivery by laser-induced hydrodynamic pressure following cavitation bubble expansion and collapse. Photoacoustic drug delivery was investigated on gelatin-based thrombus models with planar and cylindrical geometries by use of one microsecond laser pulses. Solutions of a hydrophobic dye in mineral oil permitted monitoring of delivered colored oil into clear gelatin-based thrombus models. Cavitation bubble development and photoacoustic drug delivery were visualized with flash photography. This study demonstrated that cavitation is the governing mechanism for photoacoustic drug delivery, and the deepest penetration of colored oil in gels followed the bubble collapse. Spatial distribution measurements revealed that colored oil could be driven a few millimeters into the gels in both axial and radial directions, and the penetration was less than 500 µm when the gelatin structure was not fractured.

  2. Optical diagnostics integrated with laser spark delivery system

    DOEpatents

    Yalin, Azer [Fort Collins, CO; Willson, Bryan [Fort Collins, CO; Defoort, Morgan [Fort Collins, CO; Joshi, Sachin [Fort Collins, CO; Reynolds, Adam [Fort Collins, CO

    2008-09-02

    A spark delivery system for generating a spark using a laser beam is provided, and includes a laser light source and a laser delivery assembly. The laser delivery assembly includes a hollow fiber and a launch assembly comprising launch focusing optics to input the laser beam in the hollow fiber. The laser delivery assembly further includes exit focusing optics that demagnify an exit beam of laser light from the hollow fiber, thereby increasing the intensity of the laser beam and creating a spark. Other embodiments use a fiber laser to generate a spark. Embodiments of the present invention may be used to create a spark in an engine. Yet other embodiments include collecting light from the spark or a flame resulting from the spark and conveying the light for diagnostics. Methods of using the spark delivery systems and diagnostic systems are provided.

  3. Gene delivery in tissue engineering and regenerative medicine.

    PubMed

    Fang, Y L; Chen, X G; W T, Godbey

    2015-11-01

    As a promising strategy to aid or replace tissue/organ transplantation, gene delivery has been used for regenerative medicine applications to create or restore normal function at the cell and tissue levels. Gene delivery has been successfully performed ex vivo and in vivo in these applications. Excellent proliferation capabilities and differentiation potentials render certain cells as excellent candidates for ex vivo gene delivery for regenerative medicine applications, which is why multipotent and pluripotent cells have been intensely studied in this vein. In this review, gene delivery is discussed in detail, along with its applications to tissue engineering and regenerative medicine. A definition of a stem cell is compared to a definition of a stem property, and both provide the foundation for an in-depth look at gene delivery investigations from a germ lineage angle. © 2014 Wiley Periodicals, Inc.

  4. Nanomedicine Drug Delivery across Mucous Membranes

    NASA Astrophysics Data System (ADS)

    Lancina, Michael George, III

    Control over the distribution of therapeutic compounds is a complex and somewhat overlooked field of pharmaceutical research. When swallowing a pill or receiving an injection, it is commonly assumed that drug will spread throughout the body in a more or less uniform concentration and find its way to wherever it is needed. In truth, drug biodistribuition is highly non-uniform and dependent on a large number of factors. The development of advanced drug delivery systems to control biodistribution can produce significant advances in clinical treatments without the need to discover new therapeutic compounds. This work focuses on a number of nanostructured materials designed to improve drug delivery by direct and efficient transfer of drugs across one of the body's external mucous membranes. Chapter 1 outlines the central concept that unites these studies: nanomaterials and cationic particles can be used to delivery therapeutic compounds across mucous membranes. Special attention is given to dendritic nanoparticles. In chapter 2, uses for dendrimers in ocular drug delivery are presented. The studies are divided into two main groups: topical and injectable formulations. Chapter 3 does not involve dendrimers but instead another cationic particle used in transmembrane drug delivery, chitosan. Next, a dendrimer based nanofiber mat was used to deliver anti-glaucoma drugs in chapter 4. A three week in vivo efficacy trial showed dendrimer nanofiber mats outperformed traditional eye drops in terms of intra-ocular pressure decrease in a normotensive rat model. Finally, we have developed a new dendrimer based anti-glaucoma drug in chapter 5. Collectively, these studies demonstrate some of the potential applications for nanotechnology to improve transmembrane drug delivery. These particles and fibers are able to readily adhere and penetrate across epithelial cell lays. Utilizing these materials to improve drug absorption through these portals has the potential to improve the

  5. Accurate Finite Difference Algorithms

    NASA Technical Reports Server (NTRS)

    Goodrich, John W.

    1996-01-01

    Two families of finite difference algorithms for computational aeroacoustics are presented and compared. All of the algorithms are single step explicit methods, they have the same order of accuracy in both space and time, with examples up to eleventh order, and they have multidimensional extensions. One of the algorithm families has spectral like high resolution. Propagation with high order and high resolution algorithms can produce accurate results after O(10(exp 6)) periods of propagation with eight grid points per wavelength.

  6. Radiation delivery system and method

    DOEpatents

    Sorensen, Scott A.; Robison, Thomas W.; Taylor, Craig M. V.

    2002-01-01

    A radiation delivery system and method are described. The system includes a treatment configuration such as a stent, balloon catheter, wire, ribbon, or the like, a portion of which is covered with a gold layer. Chemisorbed to the gold layer is a radiation-emitting self-assembled monolayer or a radiation-emitting polymer. The radiation delivery system is compatible with medical catheter-based technologies to provide a therapeutic dose of radiation to a lesion following an angioplasty procedure.

  7. Dual delivery systems based on polyamine analog BENSpm as prodrug and gene delivery vectors

    NASA Astrophysics Data System (ADS)

    Zhu, Yu

    Combination drug and gene therapy shows promise in cancer treatment. However, the success of such strategy requires careful selection of the therapeutic agents, as well as development of efficient delivery vectors. BENSpm (N 1, N11-bisethylnorspermine), a polyamine analogue targeting the intracellular polyamine pathway, draws our special attention because of the following reasons: (1) polyamine pathway is frequently dysregulated in cancer; (2) BENSpm exhibits multiple functions to interfere with the polyamine pathway, such as to up-regulate polyamine metabolism enzymes and down-regulate polyamine biosynthesis enzymes. Therefore BENSpm depletes all natural polyamines and leads to apoptosis and cell growth inhibition in a wide range of cancers; (3) preclinical studies proved that BENSpm can act synergistically with various chemotherapy agents, making it a promising candidate in combination therapy; (4) multiple positive charges in BENSpm enable it as a suitable building block for cationic polymers, which can be further applied to gene delivery. In this dissertation, our goal was to design dual-function delivery vector based on BENSpm that can function as a gene delivery vector and, after intracellular degradation, as an active anticancer agent targeting dysregulated polyamine metabolism. We first demonstrated strong synergism between BENSpm and a potential therapeutic gene product TRAIL. Strong synergism was obtained in both estrogen-dependent MCF-7 breast cancer cells and triple-negative MDA-MB-231 breast cancer cells. Significant dose reduction of TRAIL in combination with BENSpm in MDA-MB-231 cells, together with the fact that BENSpm rendered MCF-7 cells more sensitive to TRAIL treatment verified our rationale of designing BENSpm-based delivery platform. This was expected to be beneficial for overcoming drug resistance in chemotherapy, as well as boosting the therapeutic effect of therapeutic genes. We first designed a lipid-based BENSpm dual vector (Lipo

  8. Oral transmucosal delivery of naratriptan.

    PubMed

    Sattar, Mohammed; Lane, Majella E

    2016-11-30

    Naratriptan (NAR) is currently used as the hydrochloride salt (NAR.HCl) for the treatment of migraine and is available in tablet dosage forms for oral administration. Buccal drug delivery offers a number of advantages compared with conventional oral delivery including rapid absorption, avoidance of first pass metabolism and improved patient compliance. We have previously prepared and characterised the base form of NAR and shown that it has more favourable properties for buccal delivery compared with NAR.HCl. This study describes the design and evaluation of a range of formulations for oral transmucosal delivery of NAR base. Permeation studies were conducted using excised porcine buccal tissue mounted in Franz cells. Of the neat solvents examined, Transcutol ® P (TC) showed the greatest enhancement effects and was the vehicle in which NAR was most soluble. The mechanisms by which TC might promote permeation were further probed using binary systems containing TC with either buffer or Miglyol 812 ® (MG). Mass balance studies were also conducted for these systems. The permeation of TC as well as NAR was also monitored for TC:MG formulations. Overall, TC appears to promote enhanced membrane permeation of NAR because of its rapid uptake into the buccal tissue. Synergistic enhancement of buccal permeation was observed when TC was combined with MG and this is attributed to the increased thermodynamic activity of NAR in these formulations. Significantly enhanced permeation of NAR was achieved for TC:MG and this was also associated with less TC remaining on the tissue or in the tissue at the end of the experiment. To our knowledge this is the first report where both enhancer and active have been monitored in buccal permeation studies. The findings underline the importance of understanding the fate of vehicle components for rational formulation design of buccal delivery systems. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Strategies for Controlled Delivery of Biologics for Cartilage Repair

    PubMed Central

    Lam, Johnny; Lu, Steven; Kasper, F. Kurtis; Mikos, Antonios G.

    2014-01-01

    The delivery of biologics is an important component in the treatment of osteoarthritis and the functional restoration of articular cartilage. Numerous factors have been implicated in the cartilage repair process, but the uncontrolled delivery of these factors may not only reduce their full reparative potential and can also cause unwanted morphological effects. It is therefore imperative to consider the type of biologic to be delivered, the method of delivery, and the temporal as well as spatial presentation of the biologic to achieve the desired effect in cartilage repair. Additionally, the delivery of a single factor may not be sufficient in guiding neo-tissue formation, motivating recent research towards the delivery of multiple factors. This review will discuss the roles of various biologics involved in cartilage repair and the different methods of delivery for appropriate healing responses. A number of spatiotemporal strategies will then be emphasized for the controlled delivery of single and multiple bioactive factors in both in vitro and in vivo cartilage tissue engineering applications. PMID:24993610

  10. Biophotonic techniques for manipulation and characterization of drug delivery nanosystems in cancer therapy.

    PubMed

    Spyratou, E; Makropoulou, M; Mourelatou, E A; Demetzos, C

    2012-12-31

    Reactive oxygen species (ROS) are usually involved in two opposite procedures related to cancer: initiation, progression and metastasis of cancer, as well as in all non-surgical therapeutic approaches for cancer, including chemotherapy, radiotherapy and photodynamic therapy. This review is concentrated in new therapeutic strategies that take advantage of increased ROS in cancer cells to enhance therapeutic activity and selectivity. Novel biophotonic techniques for manipulation and characterization of drug delivery nanosystems in cancer therapy are discussed, including optical tweezers and atomic force microscopy. This review highlights how these techniques are playing a critical role in recent and future cancer fighting applications. We can conclude that Biophotonics and nanomedicine are the future for cancer biology and disease management, possessing unique potential for early detection, accurate diagnosis, dosimetry and personalized treatment of biomedical applications targeting cancer. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  11. Delivery confirmation of bolus electron conformal therapy combined with intensity modulated x-ray therapy

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

    Kavanaugh, James A.; Hogstrom, Kenneth R.; Fontenot, Jonas P.

    2013-02-15

    .1% and 94.62%, respectively, for the bolus ECT plans and 89.2% and 95.1%, respectively, for the mixed beam plans. For all regions, pass rates for the parotid and CW plans were 98.8% and 97.3%, respectively, for the bolus ECT plans and 97.5% and 95.9%, respectively, for the mixed beam plans. For the IMXT component of the mixed beam plans, pass rates for the parotid and CW plans were 93.7% and 95.8%. Conclusions: Bolus ECT and mixed beam therapy dose delivery to the phantom were more accurate than IMXT delivery, adding confidence to the use of planning, fabrication, and delivery for bolus ECT tools either alone or as part of mixed beam therapy. The methodology reported in this work could serve as a basis for future standardization of the commissioning of bolus ECT or mixed beam therapy. When applying this technology to patients, it is recommended that an electron dose algorithm more accurate than the pencil beam algorithm, e.g., a Monte Carlo algorithm or analytical transport such as the pencil beam redefinition algorithm, be used for planning to ensure the desired accuracy.« less

  12. Loop electrosurgical excision procedure and the risk for preterm delivery.

    PubMed

    Heinonen, Annu; Gissler, Mika; Riska, Annika; Paavonen, Jorma; Tapper, Anna-Maija; Jakobsson, Maija

    2013-05-01

    To estimate whether the severity of cervical intraepithelial neoplasia (CIN) and the loop electrosurgical excision procedure (LEEP) increase the risk for preterm delivery, and to evaluate the role of repeat LEEP and time interval since LEEP. This was a retrospective register-based study from Finland from 1997 to 2009. We linked Hospital Discharge Register and Finnish Medical Birth Register data. Case group women consisted of 20,011 women who underwent LEEP during the study period and their subsequent singleton deliveries in 1998-2009. Control population included women from the Medical Birth Register with no LEEP (n=430,975). The main outcome measure was preterm delivery before 37 weeks of gestation. The risk for preterm delivery increased after LEEP. Women with previous LEEP had 547 (7.2%) preterm deliveries, whereas the control population had 30,151 (4.6%) preterm deliveries (odds ratio [OR] 1.61, confidence interval [CI] 1.47-1.75, number needed to harm 38.5). The overall preterm delivery rate in the study period was 4.6% for singleton deliveries. Repeat LEEP was associated with an almost threefold risk for preterm delivery (OR 2.80, CI 2.28-3.44). The severity of CIN did not increase the risk for preterm delivery. However, with LEEP for carcinoma in situ or microinvasive cancer, the risk for preterm delivery was higher (OR 2.55, CI 1.68-3.87). The increased risk also was associated with non-CIN lesions (OR 2.04, CI 1.46-2.87). Similarly, the risk was increased after diagnostic LEEP (OR 1.39, 95% CI 1.16-1.67). Time interval since LEEP was not associated with preterm delivery. Adjusting for maternal age, parity, socioeconomic or marital status, urbanism, and previous preterm deliveries did not change the results. The risk for preterm delivery was increased after LEEP regardless of the histopathologic diagnosis. The risk was highest after repeat LEEP, which should be avoided, especially among women of reproductive age. II.

  13. Magnetic nanoparticles: Applications in gene delivery and gene therapy.

    PubMed

    Majidi, Sima; Zeinali Sehrig, Fatemeh; Samiei, Mohammad; Milani, Morteza; Abbasi, Elham; Dadashzadeh, Kianoosh; Akbarzadeh, Abolfazl

    2016-06-01

    Gene therapy is defined as the direct transfer of genetic material to tissues or cells for the treatment of inherited disorders and acquired diseases. For gene delivery, magnetic nanoparticles (MNPs) are typically combined with a delivery platform to encapsulate the gene, and promote cell uptake. Delivery technologies that have been used with MNPs contain polymeric, viral, as well as non-viral platforms. In this review, we focus on targeted gene delivery using MNPs.

  14. 30 CFR 56.6802 - Bulk delivery vehicles.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... § 56.6802 Bulk delivery vehicles. No welding or cutting shall be performed on a bulk delivery vehicle... cutting on a hollow shaft, the shaft shall be thoroughly cleaned inside and out and vented with a minimum...

  15. Assuring Quality in Online Course Delivery

    ERIC Educational Resources Information Center

    Matuga, Julia M.; Wooldridge, Deborah G.; Poirier, Sandra

    2011-01-01

    This paper examines the critical issue of assuring quality online course delivery by examining four key components of online teaching and learning. The topic of course delivery is viewed as a cultural issue that permeates processes from the design of an online course to its evaluation. First, the authors examine and review key components of and…

  16. Neonatal Resuscitation in the Delivery Room from a Tertiary Level Hospital: Risk Factors and Outcome

    PubMed Central

    Afjeh, Seyyed-Abolfazl; Sabzehei, Mohammad-Kazem; Esmaili, Fatemeh

    2013-01-01

    Objective Timely identification and prompt resuscitation of newborns in the delivery room may cause a decline in neonatal morbidity and mortality. We try to identify risk factors in mother and fetus that result in birth of newborns needing resuscitation at birth. Methods Case notes of all deliveries and neonates born from April 2010 to March 2011 in Mahdieh Medical Center (Tehran, Iran), a Level III Neonatal Intensive Care Unit, were reviewed; relevant maternal, fetal and perinatal data was extracted and analyzed. Findings During the study period, 4692 neonates were delivered; 4522 (97.7%) did not require respiratory assistance. One-hundred seven (2.3%) newborns needed resuscitation with bag and mask ventilation in the delivery unit, of whom 77 (1.6%) babies responded to bag and mask ventilation while 30 (0.65%) neonates needed endotracheal intubation and 15 (0.3%) were given chest compressions. Epinephrine/volume expander was administered to 10 (0.2%) newborns. In 17 patients resuscitation was continued for >10 mins. There was a positive correlation between the need for resuscitation and following risk factors: low birth weight, preterm labor, chorioamnionitis, pre-eclampsia, prolonged rupture of membranes, abruptio placentae, prolonged labor, meconium staining of amniotic fluid, multiple pregnancy and fetal distress. On multiple regression; low birth weight, meconium stained liquor and chorioamnionitis revealed as independent risk factors that made endotracheal intubation necessary. Conclusion Accurate identification of risk factors and anticipation at the birth of a high-risk neonate would result in adequate preparation and prompt resuscitation of neonates who need some level of intervention and thus, reducing neonatal morbidity and mortality. PMID:24910747

  17. Ion-Responsive Drug Delivery Systems.

    PubMed

    Yoshida, Takayuki; Shakushiro, Kohsuke; Sako, Kazuhiro

    2018-02-08

    Some kinds of cations and anions are contained in body fluids such as blood, interstitial fluid, gastrointestinal juice, and tears at relatively high concentration. Ionresponsive drug delivery is available to design the unique dosage formulations which provide optimized drug therapy with effective, safe and convenient dosing of drugs. The objective of the present review was to collect, summarize, and categorize recent research findings on ion-responsive drug delivery systems. Ions in body fluid/formulations caused structural changes of polymers/molecules contained in the formulations, allow formulations exhibit functions. The polymers/molecules responding to ions were ion-exchange resins/fibers, anionic or cationic polymers, polymers exhibiting transition at lower critical solution temperature, self-assemble supramolecular systems, peptides, and metalorganic frameworks. The functions of ion-responsive drug delivery systems were categorized to controlled drug release, site-specific drug release, in situ gelation, prolonged retention at the target sites, and enhancement of drug permeation. Administration of the formulations via oral, ophthalmic, transdermal, and nasal routes has showed significant advantages in the recent literatures. Many kinds of drug delivery systems responding to ions have been reported recently for several administration routes. Improvement and advancement of these systems can maximize drugs potential and contribute to patients in the world. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Trends in provider-initiated versus spontaneous preterm deliveries, 2004–2013

    PubMed Central

    Ada, Melissa L.; Hacker, Michele R.; Golen, Toni H.; Haviland, Miriam J.; Shainker, Scott A.; Burris, Heather H.

    2017-01-01

    Objectives 1) To estimate the proportion of preterm deliveries at a tertiary perinatal center that were provider-initiated vs. spontaneous before and after a 2009 policy to reduce elective early-term deliveries. 2) To evaluate if shifts in type of preterm delivery varied by race/ethnicity. Methods We performed a retrospective cohort study of preterm deliveries over a 10-year period, 2004–2013, including detailed review of 929 of 5,566 preterm deliveries to designate each delivery as provider-initiated or spontaneous. We dichotomized the time period into early (2004–2009) and late (2010–2013). We used log-binomial regression to calculate adjusted risk ratios. Results Of the 46,981 deliveries, 5,566 (11.8%) were preterm, with a significant reduction in the overall incidence of preterm delivery from 12.3% to 11.2% (P=0.0003). Among the 929 preterm deliveries analyzed, there was a reduction in the proportion of provider-initiated deliveries from 48.3% to 41.8% that was not statistically significant. The proportion of provider-initiated preterm deliveries among black, but not white, women declined from 50.8% to 39.7% (adjusted RR: 0.66; 95%CI: 0.45–0.97). This coincided with a larger reduction in overall preterm deliveries among black women (16.2% to 12.8%) vs. white women (12.3% to 11.2%) (P interaction=0.038). By 2013, the incidence of preterm deliveries had decreased for both black (12.1%) and white women (11.4%) and the difference was no longer statistically significant (P=0.7). Conclusion We found a reduction in preterm deliveries after a policy targeted at reducing elective early-term deliveries in 2009 that coincided with reductions in the proportion of provider-initiated preterm deliveries, especially among black women. PMID:28749488

  19. Mucosal delivery of liposome-chitosan nanoparticle complexes.

    PubMed

    Carvalho, Edison L S; Grenha, Ana; Remuñán-López, Carmen; Alonso, Maria José; Seijo, Begoña

    2009-01-01

    Designing adequate drug carriers has long been a major challenge for those working in drug delivery. Since drug delivery strategies have evolved for mucosal delivery as the outstanding alternative to parenteral administration, many new drug delivery systems have been developed which evidence promising properties to address specific issues. Colloidal carriers, such as nanoparticles and liposomes, have been referred to as the most valuable approaches, but still have some limitations that can become more inconvenient as a function of the specific characteristics of administration routes. To overcome these limitations, we developed a new drug delivery system that results from the combination of chitosan nanoparticles and liposomes, in an approach of combining their advantages, while avoiding their individual limitations. These lipid/chitosan nanoparticle complexes are, thus, expected to protect the encapsulated drug from harsh environmental conditions, while concomitantly providing its controlled release. To prepare these assemblies, two different strategies have been applied: one focusing on the simple hydration of a previously formed dry lipid film with a suspension of chitosan nanoparticles, and the other relying on the lyophilization of both basic structures (nanoparticles and liposomes) with a subsequent step of hydration with water. The developed systems are able to provide a controlled release of the encapsulated model peptide, insulin, evidencing release profiles that are dependent on their lipid composition. Moreover, satisfactory in vivo results have been obtained, confirming the potential of these newly developed drug delivery systems as drug carriers through distinct mucosal routes.

  20. Ultrasonic Drug Delivery – A General Review

    PubMed Central

    Pitt, William G.; Husseini, Ghaleb A.; Staples, Bryant J.

    2006-01-01

    Ultrasound (US) has an ever-increasing role in the delivery of therapeutic agents including genetic material, proteins, and chemotherapeutic agents. Cavitating gas bodies such as microbubbles are the mediators through which the energy of relatively non-interactive pressure waves is concentrated to produce forces that permeabilize cell membranes and disrupt the vesicles that carry drugs. Thus the presence of microbubbles enormously enhances delivery of genetic material, proteins and smaller chemical agents. Delivery of genetic material is greatly enhanced by ultrasound in the presence of microbubbles. Attaching the DNA directly to the microbubbles or to gas-containing liposomes enhances gene uptake even further. US-enhanced gene delivery has been studied in various tissues including cardiac, vascular, skeletal muscle, tumor and even fetal tissue. US-enhanced delivery of proteins has found most application in transdermal delivery of insulin. Cavitation events reversibly disrupt the structure of the stratus corneum to allow transport of these large molecules. Other hormones and small proteins could also be delivered transdermally. Small chemotherapeutic molecules are delivered in research settings from micelles and liposomes exposed to ultrasound. Cavitation appears to play two roles: it disrupts the structure of the carrier vesicle and releases the drug; it also makes the cell membranes and capillaries more permeable to drugs. There remains a need to better understand the physics of cavitation of microbubbles and the impact that such cavitation has upon cells and drug-carrying vesicles. PMID:16296719

  1. Electrostatic Surface Modifications to Improve Gene Delivery

    PubMed Central

    Shmueli, Ron B.; Anderson, Daniel G.

    2010-01-01

    Importance of the field Gene therapy has the potential to treat a wide variety of diseases including genetic diseases and cancer. Areas covered in this review This review introduces biomaterials used for gene delivery and then focuses on the use of electrostatic surface modifications to improve gene delivery materials. These modifications have been used to stabilize therapeutics in vivo, add cell-specific targeting ligands, and promote controlled release. Coatings of nanoparticles and microparticles as well as non-particulate surface coatings are covered in this review. Electrostatic principles are crucial for the development of multilayer delivery structures fabricated by the layer-by-layer method. What the reader will gain The reader will gain knowledge about the composition of biomaterials used for surface modifications and how these coatings and multilayers can be utilized to improve spatial control and efficiency of delivery. Examples are shown for the delivery of nucleic acids, including DNA and siRNA, to in vitro and in vivo systems. Take home message The versatile and powerful approach of electrostatic coatings and multilayers will lead to the development of enhanced gene therapies. PMID:20201712

  2. 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.

  3. Inner Ear Drug Delivery for Auditory Applications

    PubMed Central

    Swan, Erin E. Leary; Mescher, Mark J.; Sewell, William F.; Tao, Sarah L.; Borenstein, Jeffrey T.

    2008-01-01

    Many inner ear disorders cannot be adequately treated by systemic drug delivery. A blood-cochlear barrier exists, similar physiologically to the blood-brain barrier, which limits the concentration and size of molecules able to leave the circulation and gain access to the cells of the inner ear. However, research in novel therapeutics and delivery systems has led to significant progress in the development of local methods of drug delivery to the inner ear. Intratympanic approaches, which deliver therapeutics to the middle ear, rely on permeation through tissue for access to the structures of the inner ear, whereas intracochlear methods are able to directly insert drugs into the inner ear. Innovative drug delivery systems to treat various inner ear ailments such as ototoxicity, sudden sensorineural hearing loss, autoimmune inner ear disease, and for preserving neurons and regenerating sensory cells are being explored. PMID:18848590

  4. 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.

  5. Maternal obesity, caesarean delivery and caesarean delivery on maternal request: a cohort analysis from China.

    PubMed

    Zhou, Yubo; Blustein, Jan; Li, Hongtian; Ye, Rongwei; Zhu, Liping; Liu, Jianmeng

    2015-05-01

    To quantify the association between maternal obesity and caesarean delivery, particularly caesarean delivery on maternal request (CDMR), a fast-growing component of caesarean delivery in many nations. We followed 1,019,576 nulliparous women registered in the Perinatal Healthcare Surveillance System during 1993-2010. Maternal body mass index (BMI, kg/m(2) ), before pregnancy or during early pregnancy, was classified as underweight (<18.5), normal (18.5 to <23; reference), overweight (23 to <27.5), or obese (≥27.5), consistent with World Health Organization guidelines for Asian people. The association between maternal obesity and overall caesarean and its subtypes was modelled using log-binomial regression. During the 18-year period, 404,971 (39.7%) caesareans and 93,927 (9.2%) CDMRs were identified. Maternal obesity was positively associated with overall caesarean and CDMR. Adjusted risk ratios for overall caesarean in the four ascending BMI categories were 0.96 [95% confidence interval (CI) 0.94, 0.97], 1.00 (Reference), 1.16 [95% CI 1.14, 1.18], 1.39 [95% CI 1.43, 1.54], and for CDMR were 0.95 [95% CI 0.94, 0.96], 1.00 (Reference), 1.20 [95% CI 1.18, 1.22], 1.48 [95% CI 1.433, 1.54]. Positive associations were consistently found in women residing in southern and northern provinces and in subgroups stratified by year of delivery, urban or rural residence, maternal age, education, level of delivering hospital, and birthweight. In a large Chinese cohort study, maternal obesity was associated with an increased risk of caesarean delivery and its subtypes, including CDMR. Given the rising global prevalence of obesity, and in view of the growth of CDMR, it seems likely that caesarean births will increase, unless there are changes in obstetrical practice. © 2015 John Wiley & Sons Ltd.

  6. Limited Efficiency of Drug Delivery to Specific Intracellular Organelles Using Subcellularly "Targeted" Drug Delivery Systems.

    PubMed

    Maity, Amit Ranjan; Stepensky, David

    2016-01-04

    Many drugs have been designed to act on intracellular targets and to affect intracellular processes inside target cells. For the desired effects to be exerted, these drugs should permeate target cells and reach specific intracellular organelles. This subcellular drug targeting approach has been proposed for enhancement of accumulation of these drugs in target organelles and improved efficiency. This approach is based on drug encapsulation in drug delivery systems (DDSs) and/or their decoration with specific targeting moieties that are intended to enhance the drug/DDS accumulation in the intracellular organelle of interest. During recent years, there has been a constant increase in interest in DDSs targeted to specific intracellular organelles, and many different approaches have been proposed for attaining efficient drug delivery to specific organelles of interest. However, it appears that in many studies insufficient efforts have been devoted to quantitative analysis of the major formulation parameters of the DDSs disposition (efficiency of DDS endocytosis and endosomal escape, intracellular trafficking, and efficiency of DDS delivery to the target organelle) and of the resulting pharmacological effects. Thus, in many cases, claims regarding efficient delivery of drug/DDS to a specific organelle and efficient subcellular targeting appear to be exaggerated. On the basis of the available experimental data, it appears that drugs/DDS decoration with specific targeting residues can affect their intracellular fate and result in preferential drug accumulation within an organelle of interest. However, it is not clear whether these approaches will be efficient in in vivo settings and be translated into preclinical and clinical applications. Studies that quantitatively assess the mechanisms, barriers, and efficiencies of subcellular drug delivery and of the associated toxic effects are required to determine the therapeutic potential of subcellular DDS targeting.

  7. Vaginal delivery - discharge

    MedlinePlus

    ... slowly. Get plenty of rest. You can start sexual activity around 6 weeks after delivery, if the discharge or lochia has stopped. Women who breastfeed may have a lower sex drive than normal, along with vaginal dryness and pain ...

  8. The maternal childbirth experience more than a decade after delivery.

    PubMed

    Bossano, Carla M; Townsend, Kelly M; Walton, Alexandra C; Blomquist, Joan L; Handa, Victoria L

    2017-09-01

    Maternal satisfaction with the birth experience is multidimensional and influenced by many factors, including mode of delivery. To date, few studies have investigated maternal satisfaction outside of the immediate postpartum period. This study investigated whether differences in satisfaction based on mode of delivery are observed more than a decade after delivery. This was a planned, supplementary analysis of data collected for the Mothers' Outcomes after Delivery study, a longitudinal cohort study of pelvic floor disorders in parous women and their association with mode of delivery. Obstetric and demographic data were obtained through patient surveys and obstetrical chart review. Maternal satisfaction with childbirth experience was assessed via the Salmon questionnaire, administered to Mothers' Outcomes after Delivery study participants >10 years from their first delivery. This validated questionnaire yields 3 scores: fulfillment, distress, and difficulty. These 3 scores were compared by mode of delivery (cesarean prior to labor, cesarean during labor, spontaneous vaginal delivery, and operative vaginal delivery). In addition, the impact of race, age, education level, parity, episiotomy, labor induction, and duration of second stage of labor on maternal satisfaction were examined. Among 576 women, 10.1-17.5 years from delivery, significant differences in satisfaction scores were noted by delivery mode. Salmon scale scores differed between women delivering by cesarean and those delivering vaginally: women delivering vaginally reported greater fulfillment (0.40 [-0.37 to 0.92] vs 0.15 [-0.88 to 0.66], P < .001) and less distress (-0.34 [-0.88 to 0.38] vs 0.20 [-0.70 to 0.93], P < .001) than those who delivered by cesarean. Women who delivered by cesarean prior to labor reported the greatest median fulfillment scores and the lowest median difficulty scores. Median distress scores were lowest among those who delivered by spontaneous vaginal birth. Among women who

  9. Monolayer coated gold nanoparticles for delivery applications

    PubMed Central

    Rana, Subinoy; Bajaj, Avinash; Mout, Rubul; Rotello, Vincent M.

    2011-01-01

    Gold nanoparticles (AuNPs) provide attractive vehicles for delivery of drugs, genetic materials, proteins, and small molecules. AuNPs feature low core toxicity coupled with the ability to parametrically control particle size and surface properties. In this review, we focus on engineering of the AuNP surface monolayer, highlighting recent advances in tuning monolayer structures for efficient delivery of drugs and biomolecules. This review covers two broad categories of particle functionalization, organic monolayers and biomolecule coatings, and discusses their applications in drug, DNA/RNA, protein and small molecule delivery. PMID:21925556

  10. 47 CFR 64.1601 - Delivery requirements and privacy restrictions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 3 2011-10-01 2011-10-01 false Delivery requirements and privacy restrictions... Number; Privacy § 64.1601 Delivery requirements and privacy restrictions. (a) Delivery. Except as... party number (CPN) associated with an interstate call to interconnecting carriers. (b) Privacy. Except...

  11. 47 CFR 64.1601 - Delivery requirements and privacy restrictions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Delivery requirements and privacy restrictions... Number; Privacy § 64.1601 Delivery requirements and privacy restrictions. (a) Delivery. Except as... party number (CPN) associated with an interstate call to interconnecting carriers. (b) Privacy. Except...

  12. Calibrating GPS With TWSTFT For Accurate Time Transfer

    DTIC Science & Technology

    2008-12-01

    40th Annual Precise Time and Time Interval (PTTI) Meeting 577 CALIBRATING GPS WITH TWSTFT FOR ACCURATE TIME TRANSFER Z. Jiang1 and...primary time transfer techniques are GPS and TWSTFT (Two-Way Satellite Time and Frequency Transfer, TW for short). 83% of UTC time links are...Calibrating GPS With TWSTFT For Accurate Time Transfer 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT

  13. Mental models accurately predict emotion transitions.

    PubMed

    Thornton, Mark A; Tamir, Diana I

    2017-06-06

    Successful social interactions depend on people's ability to predict others' future actions and emotions. People possess many mechanisms for perceiving others' current emotional states, but how might they use this information to predict others' future states? We hypothesized that people might capitalize on an overlooked aspect of affective experience: current emotions predict future emotions. By attending to regularities in emotion transitions, perceivers might develop accurate mental models of others' emotional dynamics. People could then use these mental models of emotion transitions to predict others' future emotions from currently observable emotions. To test this hypothesis, studies 1-3 used data from three extant experience-sampling datasets to establish the actual rates of emotional transitions. We then collected three parallel datasets in which participants rated the transition likelihoods between the same set of emotions. Participants' ratings of emotion transitions predicted others' experienced transitional likelihoods with high accuracy. Study 4 demonstrated that four conceptual dimensions of mental state representation-valence, social impact, rationality, and human mind-inform participants' mental models. Study 5 used 2 million emotion reports on the Experience Project to replicate both of these findings: again people reported accurate models of emotion transitions, and these models were informed by the same four conceptual dimensions. Importantly, neither these conceptual dimensions nor holistic similarity could fully explain participants' accuracy, suggesting that their mental models contain accurate information about emotion dynamics above and beyond what might be predicted by static emotion knowledge alone.

  14. Mental models accurately predict emotion transitions

    PubMed Central

    Thornton, Mark A.; Tamir, Diana I.

    2017-01-01

    Successful social interactions depend on people’s ability to predict others’ future actions and emotions. People possess many mechanisms for perceiving others’ current emotional states, but how might they use this information to predict others’ future states? We hypothesized that people might capitalize on an overlooked aspect of affective experience: current emotions predict future emotions. By attending to regularities in emotion transitions, perceivers might develop accurate mental models of others’ emotional dynamics. People could then use these mental models of emotion transitions to predict others’ future emotions from currently observable emotions. To test this hypothesis, studies 1–3 used data from three extant experience-sampling datasets to establish the actual rates of emotional transitions. We then collected three parallel datasets in which participants rated the transition likelihoods between the same set of emotions. Participants’ ratings of emotion transitions predicted others’ experienced transitional likelihoods with high accuracy. Study 4 demonstrated that four conceptual dimensions of mental state representation—valence, social impact, rationality, and human mind—inform participants’ mental models. Study 5 used 2 million emotion reports on the Experience Project to replicate both of these findings: again people reported accurate models of emotion transitions, and these models were informed by the same four conceptual dimensions. Importantly, neither these conceptual dimensions nor holistic similarity could fully explain participants’ accuracy, suggesting that their mental models contain accurate information about emotion dynamics above and beyond what might be predicted by static emotion knowledge alone. PMID:28533373

  15. Methods and metrics challenges of delivery-system research

    PubMed Central

    2012-01-01

    Background Many delivery-system interventions are fundamentally about change in social systems (both planned and unplanned). This systems perspective raises a number of methodological challenges for studying the effects of delivery-system change--particularly for answering questions related to whether the change will work under different conditions and how the change is integrated (or not) into the operating context of the delivery system. Methods The purpose of this paper is to describe the methodological and measurement challenges posed by five key issues in delivery-system research: (1) modeling intervention context; (2) measuring readiness for change; (3) assessing intervention fidelity and sustainability; (4) assessing complex, multicomponent interventions; and (5) incorporating time in delivery-system models to discuss recommendations for addressing these issues. For each issue, we provide recommendations for how research may be designed and implemented to overcome these challenges. Results and conclusions We suggest that a more refined understanding of the mechanisms underlying delivery-system interventions (treatment theory) and the ways in which outcomes for different classes of individuals change over time are fundamental starting points for capturing the heterogeneity in samples of individuals exposed to delivery-system interventions. To support the research recommendations outlined in this paper and to advance understanding of the "why" and "how" questions of delivery-system change and their effects, funding agencies should consider supporting studies with larger organizational sample sizes; longer duration; and nontraditional, mixed-methods designs. A version of this paper was prepared under contract with the Agency for Healthcare Research and Quality (AHRQ), US Department of Health and Human Services for presentation and discussion at a meeting on "The Challenge and Promise of Delivery System Research," held in Sterling, VA, on February 16-17, 2011

  16. Liposomal systems as viable drug delivery technology for skin cancer sites with an outlook on lipid-based delivery vehicles and diagnostic imaging inputs for skin conditions'.

    PubMed

    Akhtar, Naseem; Khan, Riaz A

    2016-10-01

    Skin cancer is among one of the most common human malignancies wide-spread world-over with mortality statistics rising continuously at an alarming rate. The increasing frequency of these malignancies has marked the need for adopting effective treatment plan coupled with better and site-specific delivery options for the desired therapeutic agent's availability at the affected site. The concurrent delivery approaches to cancerous tissues are under constant challenge and, as a result, are evolving and gaining advancements in terms of delivery modes, therapeutic agents and site-specificity of the therapeutics delivery. The lipid-based liposomal drug delivery is an attractive and emerging option, and which is meticulously shaping up beyond a threshold level to a promising, and viable route for the effective delivery of therapeutic agents and other required injuctions to the skin cancer. An update on liposomal delivery of chemotherapeutic agents, natural-origin compounds, photosensitizer, and DNA repair enzymes as well as other desirable and typical delivery modes employed in drug delivery and in the treatment of skin cancers is discussed in details. Moreover, liposomal delivery of nucleic acid-based therapeutics, i.e., small interfering RNA (siRNA), mRNA therapy, and RGD-linked liposomes are among the other promising novel technology under constant development. The current clinical applicability, viable clinical plans, future prospects including transport feasibility of delivery vesicles and imaging techniques in conjunction with the therapeutic agents is also discussed. The ongoing innovations in liposomal drug delivery technology for skin cancers hold promise for further development of the methodology for better, more effective and site-specific delivery as part of the better treatment plan by ensuring faster drug transport, better and full payload delivery with enough and required concentration of the dose. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Temporal resolution required for accurate evaluation of the interplay effect in spot scanning proton therapy

    NASA Astrophysics Data System (ADS)

    Seo, Jeongmin; Han, Min Cheol; Yeom, Yeon Soo; Lee, Hyun Su; Kim, Chan Hyeong; Jeong, Jong Hwi; Kim, SeongHoon

    2017-04-01

    In proton therapy, the spot scanning method is known to suffer from the interplay effect induced from the independent movements of the proton beam and the organs in the patient during the treatment. To study the interplay effect, several investigators have performed four-dimensional (4D) dose calculations with some limited temporal resolutions (4 or 10 phases per respiratory cycle) by using the 4D computed tomography (CT) images of the patient; however, the validity of the limited temporal resolutions has not been confirmed. The aim of the present study is to determine whether the previous temporal resolutions (4 or 10 phases per respiratory cycle) are really high enough for adequate study of the interplay effect in spot scanning proton therapy. For this study, a series of 4D dose calculations were performed with a virtual water phantom moving in the vertical direction during dose delivery. The dose distributions were calculated for different temporal resolutions (4, 10, 25, 50, and 100 phases per respiratory cycle), and the calculated dose distributions were compared with the reference dose distribution, which was calculated using an almost continuously-moving water phantom ( i.e., 1000 phases per respiratory cycle). The results of the present study show that the temporal resolutions of 4 and 10 phases per respiratory cycle are not high enough for an accurate evaluation of the interplay effect for spot scanning proton therapy. The temporal resolution should be at least 14 and 17 phases per respiratory cycle for 10-mm and 20-mm movement amplitudes, respectively, even for rigid movement ( i.e., without deformation) of the homogeneous water phantom considered in the present study. We believe that even higher temporal resolutions are needed for an accurate evaluation of the interplay effect in the human body, in which the organs are inhomogeneous and deform during movement.

  18. Light-switchable systems for remotely controlled drug delivery.

    PubMed

    Shim, Gayong; Ko, Seungbeom; Kim, Dongyoon; Le, Quoc-Viet; Park, Gyu Thae; Lee, Jaiwoo; Kwon, Taekhyun; Choi, Han-Gon; Kim, Young Bong; Oh, Yu-Kyoung

    2017-12-10

    Light-switchable systems have recently received attention as a new mode of remotely controlled drug delivery. In the past, a multitude of nanomedicine studies have sought to enhance the specificity of drug delivery to target sites by focusing on receptors overexpressed on malignant cells or environmental features of diseases sites. Despite these immense efforts, however, there are few clinically available nanomedicines. We need a paradigm shift in drug delivery. One strategy that may overcome the limitations of pathophysiology-based drug delivery is the use of remotely controlled delivery technology. Unlike pathophysiology-based active drug targeting strategies, light-switchable systems are not affected by the heterogeneity of cells, tissue types, and/or microenvironments. Instead, they are triggered by remote light (i.e., near-infrared) stimuli, which are absorbed by photoresponsive molecules or three-dimensional nanostructures. The sequential conversion of light to heat or reactive oxygen species can activate drug release and allow it to be spatio-temporally controlled. Light-switchable systems have been used to activate endosomal drug escape, modulate the release of chemical and biological drugs, and alter nanoparticle structures to control the release rates of drugs. This review will address the limitations of pathophysiology-based drug delivery systems, the current status of light-based remote-switch systems, and future directions in the application of light-switchable systems for remotely controlled drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. 22 CFR 123.14 - Import certificate/delivery verification procedure.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... REGULATIONS LICENSES FOR THE EXPORT OF DEFENSE ARTICLES § 123.14 Import certificate/delivery verification procedure. (a) The Import Certificate/Delivery Verification Procedure is designed to assure that a commodity... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Import certificate/delivery verification...

  20. 22 CFR 123.14 - Import certificate/delivery verification procedure.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... REGULATIONS LICENSES FOR THE EXPORT OF DEFENSE ARTICLES § 123.14 Import certificate/delivery verification procedure. (a) The Import Certificate/Delivery Verification Procedure is designed to assure that a commodity... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Import certificate/delivery verification...

  1. Convection-enhanced delivery of SN-38-loaded polymeric micelles (NK012) enables consistent distribution of SN-38 and is effective against rodent intracranial brain tumor models.

    PubMed

    Zhang, Rong; Saito, Ryuta; Mano, Yui; Sumiyoshi, Akira; Kanamori, Masayuki; Sonoda, Yukihiko; Kawashima, Ryuta; Tominaga, Teiji

    2016-10-01

    Convection-enhanced delivery (CED) of therapeutic agents is a promising local delivery technique that has been extensively studied as a treatment for CNS diseases over the last two decades. One continuing challenge of CED is accurate and consistent delivery of the agents to the target. The present study focused on a new type of therapeutic agent, NK012, a novel SN-38-loaded polymeric micelle. Local delivery profiles of NK012 and SN-38 were studied using rodent brain and intracranial rodent brain tumor models. First, the cytotoxicity of NK012 against glioma cell lines was determined in vitro. Proliferations of glioma cells were significantly reduced after exposure to NK012. Then, the distribution and local toxicity after CED delivery of NK012 and SN-38 were evaluated in vivo. Volume of distribution of NK012 after CED was much larger than that of SN-38. Histological examination revealed minimum brain tissue damage in rat brains after delivery of 40 µg NK012 but severe damage with SN-38 at the same dose. Subsequently, the efficacy of NK012 delivered via CED was tested in 9L and U87MG rodent orthotopic brain tumor models. CED of NK012 displayed excellent efficacy in the 9L and U87MG orthotopic brain tumor models. Furthermore, NK012 and gadolinium diamide were co-delivered via CED to monitor the NK012 distribution using MRI. Volume of NK012 distribution evaluated by histology and MRI showed excellent agreement. CED of NK012 represents an effective treatment option for malignant gliomas. MRI-guided CED of NK012 has potential for clinical application.

  2. Introduction for Design of Nanoparticle Based Drug Delivery Systems.

    PubMed

    Edgar, Jun Yan Chan; Wang, Hui

    2017-01-01

    Conventional drug delivery systems contain numerous limitations such as limited targeting, low therapeutic indices, poor water solubility, and the induction of drug resistances. In order to overcome the drawbacks of conventional pathway of drug delivery, nanoparticle delivery systems are therefore designed and used as the drug carriers. Nanoparticle based drug delivery systems have been rapidly growing and are being applied to various sections of biomedicine. Drug nanocarriers based on dendrimers, liposomes, self-assembling peptides, watersoluble polymers, and block copolymer micelles are the most extensively studied types of drug delivery systems and some of them are being used in clinical therapy. In particular for cancer therapy, antineoplastic drugs are taking advantage of nanoparticulate drug carriers to improve the cure efficacy. Nanoparticle based drug carriers are capable of improving the therapeutic effectiveness of the drugs by using active targeting for the site-specific delivery, passive targeting mechanisms such as enhanced permeability and retention (EPR), de novo synthesis and uptake of low density liposome in cancer cells or by being water-soluble to improve the suboptimal pharmacokinetics in limited water-soluble delivery methods. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. 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

  4. Role of Nanodiamonds in Drug Delivery and Stem Cell Therapy.

    PubMed

    Ansari, Shakeel Ahmed; Satar, Rukhsana; Jafri, Mohammad Alam; Rasool, Mahmood; Ahmad, Waseem; Kashif Zaidi, Syed

    2016-09-01

    The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Nanodiamonds (NDs) have contributed significantly in the development of highly efficient and successful drug delivery systems, and in stem cell therapy. Drug delivery through NDs is an intricate and complex process that deserves special attention to unravel underlying molecular mechanisms in order to overcome certain bottlenecks associated with it. It has already been established that NDs based drug delivery systems have excellent biocompatibility, nontoxicity, photostability and facile surface functionalization properties. There is mounting evidence that suggests that such conjugated delivery systems well retain the properties of nanoparticles like small size, large surface area to volume ratio that provide greater biocatalytic activity to the attached drug in terms of selectivity, loading and stability. NDs based drug delivery systems may form the basis for the development of effective novel drug delivery vehicles with salient features that may facilitate their utility in fluorescence imaging, target specificity and sustainedrelease.

  5. Oleic acid-enhanced transdermal delivery pathways of fluorescent nanoparticles

    NASA Astrophysics Data System (ADS)

    Lo, Wen; Ghazaryan, Ara; Tso, Chien-Hsin; Hu, Po-Sheng; Chen, Wei-Liang; Kuo, Tsung-Rong; Lin, Sung-Jan; Chen, Shean-Jen; Chen, Chia-Chun; Dong, Chen-Yuan

    2012-05-01

    Transdermal delivery of nanocarriers provides an alternative pathway to transport therapeutic agents, alleviating pain, improving compliance of patients, and increasing overall effectiveness of delivery. In this work, enhancement of transdermal delivery of fluorescent nanoparticles and sulforhodamine B with assistance of oleic acid was visualized utilizing multiphoton microscopy (MPM) and analyzed quantitatively using multi-photon excitation-induced fluorescent signals. Results of MPM imaging and MPM intensity-based spatial depth-dependent analysis showed that oleic acid is effective in facilitating transdermal delivery of nanoparticles.

  6. Pairing Coral Geochemical Analyses with an Ecosystem Services Model to Assess Drivers and Impacts of Sediment Delivery within Micronesia's Largest Estuary, Ngeremeduu Bay

    NASA Astrophysics Data System (ADS)

    Lewis, S.; Dunbar, R. B.; Mucciarone, D.; Barkdull, M.

    2017-12-01

    VEST sediment delivery model results suggest fires increases sediment exportation by an order of magnitude compared with the other major land-use activities. A refined measure of LULC from a novel database (earth-moving permits) will be used to develop a more accurate depiction of sediment delivery to estuarine and coastal habitats.

  7. DNA barcode data accurately assign higher spider taxa

    PubMed Central

    Coddington, Jonathan A.; Agnarsson, Ingi; Cheng, Ren-Chung; Čandek, Klemen; Driskell, Amy; Frick, Holger; Gregorič, Matjaž; Kostanjšek, Rok; Kropf, Christian; Kweskin, Matthew; Lokovšek, Tjaša; Pipan, Miha; Vidergar, Nina

    2016-01-01

    The use of unique DNA sequences as a method for taxonomic identification is no longer fundamentally controversial, even though debate continues on the best markers, methods, and technology to use. Although both existing databanks such as GenBank and BOLD, as well as reference taxonomies, are imperfect, in best case scenarios “barcodes” (whether single or multiple, organelle or nuclear, loci) clearly are an increasingly fast and inexpensive method of identification, especially as compared to manual identification of unknowns by increasingly rare expert taxonomists. Because most species on Earth are undescribed, a complete reference database at the species level is impractical in the near term. The question therefore arises whether unidentified species can, using DNA barcodes, be accurately assigned to more inclusive groups such as genera and families—taxonomic ranks of putatively monophyletic groups for which the global inventory is more complete and stable. We used a carefully chosen test library of CO1 sequences from 49 families, 313 genera, and 816 species of spiders to assess the accuracy of genus and family-level assignment. We used BLAST queries of each sequence against the entire library and got the top ten hits. The percent sequence identity was reported from these hits (PIdent, range 75–100%). Accurate assignment of higher taxa (PIdent above which errors totaled less than 5%) occurred for genera at PIdent values >95 and families at PIdent values ≥ 91, suggesting these as heuristic thresholds for accurate generic and familial identifications in spiders. Accuracy of identification increases with numbers of species/genus and genera/family in the library; above five genera per family and fifteen species per genus all higher taxon assignments were correct. We propose that using percent sequence identity between conventional barcode sequences may be a feasible and reasonably accurate method to identify animals to family/genus. However, the quality of

  8. Radiographic film dosimetry of proton beams for depth‐dose constancy check and beam profile measurement

    PubMed Central

    Teran, Anthony; Ghebremedhin, Abiel; Johnson, Matt; Patyal, Baldev

    2015-01-01

    dose was reproducible within 10%. These large discrepancies were identified to have been contributed by film processor uncertainty across a layer of film and the misalignment of film edge to the frontal phantom surface. The deviations could drop from 5 to 2 mm in SOBP and from 10% to 4.5% at 5 cm depth in a well‐controlled processor condition (i.e., warm up). In addition to the validation of the calibration method done by the DD measurements, the concurrent film and IC measurement independently validated the model by showing the constancy of depth‐dependent calibration factors. For profile measurement, the film showed good agreement with ion chamber measurement. In agreement with the experimental findings, computationally obtained ratio of film dose to water dose assisted understanding of the trend of the film response by revealing relatively large and small variances of the response for DD and beam profile measurements, respectively. Conclusions are as follows. For proton beams, radiographic film proved to offer accurate beam profile measurements. The adaptive calibration method proposed in this study was validated. Using the method, film dosimetry could offer reasonably accurate DD constancy checks, when provided with a well‐controlled processor condition. Although the processor warming up can promote a uniform processing across a single layer of the film, the processing remains as a challenge. PACS number: 87 PMID:26103499

  9. 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

  10. Biodegradable nanoparticles for intracellular delivery of antimicrobial agents.

    PubMed

    Xie, Shuyu; Tao, Yanfei; Pan, Yuanhu; Qu, Wei; Cheng, Guyue; Huang, Lingli; Chen, Dongmei; Wang, Xu; Liu, Zhenli; Yuan, Zonghui

    2014-08-10

    Biodegradable nanoparticles have emerged as a promising strategy for ferrying antimicrobial agents into specific cells due to their unique properties. This review discusses the current progress and challenges of biodegradable nanoparticles for intracellular antimicrobial delivery to understand design principles for the development of ideal nanocarriers. The intracellular delivery performances of biodegradable nanoparticles for diverse antimicrobial agents are first summarized. Second, the cellular internalization and intracellular trafficking, degradation and release kinetics of nanoparticles as well as their relation with intracellular delivery of encapsulated antimicrobial agents are provided. Third, the influences of nanoparticle properties on the cellular internalization and intracellular fate of nanoparticles and their payload antimicrobial agents are discussed. Finally, the challenges and perspectives of nanoparticles for intracellular delivery of antimicrobial agents are addressed. The review will be helpful to the scientists who are interested in searching for more efficient nanosystem strategies for intracellular delivery of antimicrobial agents. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Transdermal delivery of biomacromolecules using lipid-like nanoparticles

    NASA Astrophysics Data System (ADS)

    Bello, Evelyn A.

    The transdermal delivery of biomacromolecules, including proteins and nucleic acids, is challenging, owing to their large size and the penetration-resistant nature of the stratum corneum. Thus, an urgent need exists for the development of transdermal delivery methodologies. This research focuses on the use of cationic lipid-like nanoparticles (lipidoids) for the transdermal delivery of proteins, and establishes an in vitro model for the study. The lipidoids used were first combinatorially designed and synthesized; afterwards, they were employed for protein encapsulation in a vesicular system. A skin penetration study demonstrated that lipidoids enhance penetration depth in a pig skin model, overcoming the barrier that the stratum corneum presents. This research has successfully identified active lipidoids capable of efficiently penetrating the skin; therefore, loading proteins into lipidoid nanoparticles will facilitate the transdermal delivery of proteins. Membrane diffusion experiments were used to confirm the results. This research has confirmed that lipidoids are a suitable material for transdermal protein delivery enhancement.

  12. 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

  13. Investigation of a thiolated polymer in gene delivery

    NASA Astrophysics Data System (ADS)

    Bacalocostantis, Irene

    Thiol-containing bioreducible polymers show significant potential as delivery vectors in gene therapy, a rapidly growing field which seeks to treat genetic-based disorders by delivering functional synthetic genes to diseased cells. Studies have shown that thiolated polymers exhibit improved biodegradability and prolonged in vivo circulation times over non-thiolated polymers. However, the extent to which thiol concentrations impact the carrier's delivery potential has not been well explored. The aim of this dissertation is to investigate how relative concentrations of free thiols and disulfide crosslinks impact a polymeric carriers delivery performance with respect to DNA packaging, complex stability, cargo protection, gene release, internalization efficiency and cytotoxicity. To accomplish this goal, several fluorescent polymers containing varying concentrations of thiol groups were synthesized by conjugating thiol-pendant chains onto the primary amines of cationic poly(allylamine). In vitro delivery assays and characterization techniques were employed to assess the effect of thiols in gene delivery.

  14. Infrared free electron laser enhanced transdermal drug delivery

    NASA Astrophysics Data System (ADS)

    Awazu, Kunio; Uchizono, Takeyuki; Suzuki, Sachiko; Yoshikawa, Kazushi

    2005-08-01

    It is necessary to control enhancement of transdermal drug delivery with non-invasive. The present study was investigated to assess the effectivity of enhancing the drug delivery by irradiating 6-μm region mid infrared free electron laser (MIR-FEL). The enhancement of transdermal drug (lidocaine) delivery of the samples (hairless mouse skin) irradiated with lasers was examined for flux (μg/cm2/h) and total penetration amount (μg/cm2) of lidocaine by High performance Liquid Chromatography (HPLC). The flux and total amount penatration date was enhanced 200-300 fold faster than the control date by the laser irradiation. FEL irradiating had the stratum corneum, and had the less thermal damage in epidermis. The effect of 6-μm region MIR-FEL has the enhancement of transdermal drug delivery without removing the stratum corneum because it has the less thermal damage. It leads to enhancement drug delivery system with non-invasive laser treatment.

  15. Novel Strategies for Anterior Segment Ocular Drug Delivery

    PubMed Central

    Cholkar, Kishore; Patel, Sulabh P.; Vadlapudi, Aswani Dutt

    2013-01-01

    Abstract Research advancements in pharmaceutical sciences have led to the development of new strategies in drug delivery to anterior segment. Designing a new delivery system that can efficiently target the diseased anterior ocular tissue, generate high drug levels, and maintain prolonged and effective concentrations with no or minimal side effects is the major focus of current research. Drug delivery by traditional method of administration via topical dosing is impeded by ocular static and dynamic barriers. Various products have been introduced into the market that prolong drug retention in the precorneal pocket and to improve bioavailability. However, there is a need of a delivery system that can provide controlled release to treat chronic ocular diseases with a reduced dosing frequency without causing any visual disturbances. This review provides an overview of anterior ocular barriers along with strategies to overcome these ocular barriers and deliver therapeutic agents to the affected anterior ocular tissue with a special emphasis on nanotechnology-based drug delivery approaches. PMID:23215539

  16. Advances in bioresponsive closed-loop drug delivery systems.

    PubMed

    Yu, Jicheng; Zhang, Yuqi; Yan, Junjie; Kahkoska, Anna R; Gu, Zhen

    2017-11-27

    Controlled drug delivery systems are able to improve efficacy and safety of therapeutics by optimizing the duration and kinetics of release. Among them, closed-loop delivery strategies, also known as self-regulated administration, have proven to be a practical tool for homeostatic regulation, by tuning drug release as a function of biosignals relevant to physiological and pathological processes. A typical example is glucose-responsive insulin delivery system, which can mimic the pancreatic beta cells to release insulin with a proper dose at a proper time point by responding to plasma glucose levels. Similar self-regulated systems are also important in the treatment of other diseases including thrombosis and bacterial infection. In this review, we survey the recent advances in bioresponsive closed-loop drug delivery systems, including glucose-responsive, enzyme-activated, and other biosignal-mediated delivery systems. We also discuss the future opportunities and challenges in this field. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. 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.

  18. 47 CFR 64.1601 - Delivery requirements and privacy restrictions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 3 2014-10-01 2014-10-01 false Delivery requirements and privacy restrictions... Number; Privacy § 64.1601 Delivery requirements and privacy restrictions. (a) Delivery. Except as... and transmission technology used by the carrier or VoIP provider. (b) Privacy. Except as provided in...

  19. 47 CFR 64.1601 - Delivery requirements and privacy restrictions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 3 2012-10-01 2012-10-01 false Delivery requirements and privacy restrictions... Number; Privacy § 64.1601 Delivery requirements and privacy restrictions. (a) Delivery. Except as... and transmission technology used by the carrier or VoIP provider. (b) Privacy. Except as provided in...

  20. 47 CFR 64.1601 - Delivery requirements and privacy restrictions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 3 2013-10-01 2013-10-01 false Delivery requirements and privacy restrictions... Number; Privacy § 64.1601 Delivery requirements and privacy restrictions. (a) Delivery. Except as... and transmission technology used by the carrier or VoIP provider. (b) Privacy. Except as provided in...