42 CFR 447.54 - Maximum allowable and nominal charges.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., any co-payments it imposes under a fee-for-service delivery system do not exceed the amounts shown in... Deductible, Coinsurance, Co-Payment Or Similar Cost-Sharing Charge § 447.54 Maximum allowable and nominal... paragraph (a)(3)(i) of this section for comparable services under a fee-for-service delivery system. When...

Recent Advancement and Technological Aspects of Pulsatile Drug Delivery System - A Laconic Review.

PubMed

Pandit, Vinay; Kumar, Ajay; Ashawat, Mahendra S; Verma, Chander P; Kumar, Pravin

2017-01-01

Pulsatile drug delivery system (PDDS) shows potential significance in the field of drug delivery to release the maximum amount of drug at a definite site and at specific time. PDDS are mainly time controlled delivery devices having a definite pause period for drug release, which is not affected by acidity, alkalinity, motility and enzymes present in the gastrointestinal tract. Pulsatile medication possess the potential to deliver the drugs in the therapy of diseases where drug dose is essential during sleep, drugs having greater first pass metabolism and absorption at precise location in digestive tract. The review article, discuss the general concepts, marketed formulations and patents or any other recent advancement in pulsatile release technology. It also highlights on diseases requiring therapy by pulsatile release, various researches on herbal pulsatile formulations and quality control aspects of PDDS. Pulsatile medication possess the potential to deliver the drugs in the therapy of diseases where drug dose is essential during sleep, drugs having greater first pass metabolism and absorption at precise location in digestive tract. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Simultaneous minimization of leaf travel distance and tongue-and-groove effect for segmental intensity-modulated radiation therapy.

PubMed

Dai, Jianrong; Que, William

2004-12-07

This paper introduces a method to simultaneously minimize the leaf travel distance and the tongue-and-groove effect for IMRT leaf sequences to be delivered in segmental mode. The basic idea is to add a large enough number of openings through cutting or splitting existing openings for those leaf pairs with openings fewer than the number of segments so that all leaf pairs have the same number of openings. The cutting positions are optimally determined with a simulated annealing technique called adaptive simulated annealing. The optimization goal is set to minimize the weighted summation of the leaf travel distance and tongue-and-groove effect. Its performance was evaluated with 19 beams from three clinical cases; one brain, one head-and-neck and one prostate case. The results show that it can reduce the leaf travel distance and (or) tongue-and-groove effect; the reduction of the leaf travel distance reaches its maximum of about 50% when minimized alone; the reduction of the tongue-and-groove reaches its maximum of about 70% when minimized alone. The maximum reduction in the leaf travel distance translates to a 1 to 2 min reduction in treatment delivery time per fraction, depending on leaf speed. If the method is implemented clinically, it could result in significant savings in treatment delivery time, and also result in significant reduction in the wear-and-tear of MLC mechanics.

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

Liang, Xiaodong, E-mail: lxdctopone@sina.com; Ni, Lingqin; Hu, Wei

The objective of this study was to evaluate the dose conformity and feasibility of whole-brain radiotherapy with a simultaneous integrated boost by forward intensity-modulated radiation therapy in patients with 1 to 3 brain metastases. Forward intensity-modulated radiation therapy plans were generated for 10 patients with 1 to 3 brain metastases on Pinnacle 6.2 Treatment Planning System. The prescribed dose was 30 Gy to the whole brain (planning target volume [PTV]{sub wbrt}) and 40 Gy to individual brain metastases (PTV{sub boost}) simultaneously, and both doses were given in 10 fractions. The maximum diameters of individual brain metastases ranged from 1.6 tomore » 6 cm, and the summated PTVs per patient ranged from 1.62 to 69.81 cm{sup 3}. Conformity and feasibility were evaluated regarding conformation number and treatment delivery time. One hundred percent volume of the PTV{sub boost} received at least 95% of the prescribed dose in all cases. The maximum doses were less than 110% of the prescribed dose to the PTV{sub boost}, and all of the hot spots were within the PTV{sub boost}. The volume of the PTV{sub wbrt} that received at least 95% of the prescribed dose ranged from 99.2% to 100%. The mean values of conformation number were 0.682. The mean treatment delivery time was 2.79 minutes. Ten beams were used on an average in these plans. Whole-brain radiotherapy with a simultaneous integrated boost by forward intensity-modulated radiation therapy in 1 to 3 brain metastases is feasible, and treatment delivery time is short.« less

Comparative Study of Oral and Vaginal Misoprostol for Induction of Labour, Maternal and Foetal Outcome

PubMed Central

Komala, Kambhampati; Reddy, Meherlatha; Quadri, Iqbal Jehan; B., Suneetha; V., Ramya

2013-01-01

Background: Misoprostol is a new promising agent for cervical ripening and induction of labour .The ideal dose, route and frequency of administration of misoprostol are still under investigation. Although, vaginal application of misoprostol has been validated as a reasonable mean of induction, there is a patient resistance to digital examination and there is a risk of ascending infection. For this reason, oral administration of misoprostol for cervical ripening and labour induction has been tried. Aims and Objectives: To compare 50μg of oral misoprostol versus 25μg of intravaginal misoprostol for induction of labour at term and maternal, foetal outcomes. Methods: Two hundred women who were at term, with indication for induction of labour and Bishop scores of ≤5 were randomly assigned to receive misoprostol 50μg or 25μg intravaginal, every 4-6 hours, for a maximum of 5 doses. In either group, pregnant females with inadequate uterine contractions despite being given maximum 5 doses of misoprostol, were augmented using oxytocin. The primary outcome measure was time-interval from induction to vaginal delivery and vaginal delivery rate within 24 hours. Results: The median induction to vaginal delivery time in oral group (12.92h) and vaginal group (14.04 h) was not significant. Oral misoprostol resulted in more number of vaginal deliveries as compared to vaginal misoprostol (94% as compared to 86%), which was not significant. There was a significantly higher incidence of uterine tachysystole in the vaginal group, as compared to oral group. There were no significant differences between the groups with respect to oxytocin augmentation, caesarean section rate, analgesic requirement and neonatal outcome. Conclusion: Oral misoprostol is as efficacious as vaginal misoprostol because of shorter induction delivery interval, lower caesarean section rates, and lower incidence of failed induction rates. Lower incidence of foetal distress and easy intake are observed if the drug is administered orally. PMID:24551660

Optimizing light delivery for a photoacoustic surgical system

NASA Astrophysics Data System (ADS)

Eddins, Blackberrie; Lediju Bell, Muyinatu A.

2017-03-01

This work explores light delivery optimization for a photoacoustic surgical system previously proposed to provide real-time, intraoperative visualization of the internal carotid arteries hidden by bone during minimally invasive neurosurgeries. Monte Carlo simulations were employed to study 3D light propagation in tissue. For a 2.4 mm diameter drill shaft and 2.9 mm spherical drill tip, the optimal fiber distance from the drill shaft was 2 mm, determined from the maximum normalized fluence seen by the artery. A single fiber was insufficient to deliver light to arteries separated by a minimum of 8 mm. Using similar drill geometry and the optimal 2 mm fiber-to-drill shaft distance, Zemax ray tracing simulations were employed to propagate a 950 nm wavelength Gaussian beam through one or more 600 μm core diameter optical fibers, and the resulting optical beam profile was detected on the representative bone surface. For equally spaced fibers, a single merged optical profile formed with 7 or more fibers, determined by thresholding the resulting light profile images at 1/e times the maximum intensity. The corresponding spot size was larger than that of a single fiber transmitting the same input energy, thus reducing the fluence delivered to the sphenoid bone and enabling higher energies within safety limits. A prototype was designed and built based on these optimization parameters. The methodology we used to optimize our light delivery system to surround surgical tools is generalizable to multiple interventional photoacoustic applications.

SU-E-T-755: Timing Characteristics of Proton and Carbon Ion Treatments Using a Synchrotron and Modulated Scanning

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

Zhao, J; Li, Y; Huang, Z

2015-06-15

Purpose: The time required to deliver a treatment impacts not only the number of patients that can be treated each day but also the accuracy of delivery due to potential movements of patient tissues. Both macroscopic and microscopic timing characteristics of a beam delivery system were studied to examine their impacts on patient treatments. Methods: 35 patients were treated during a clinical trial to demonstrate safety and efficacy of a Siemens Iontris system prior to receiving approval from the Chinese Food and Drug Administration. The system has a variable cycle time and can provide proton beams from 48 to 221more » MeV/n and carbon ions from 86 to 430 MeV/n. A modulated scanning beam delivery technique is used where the beam remains stationary at each spot aiming location and is not turned off while the spot quickly moves from one aiming location to the next. The treatment log files for 28 of the trial patients were analyzed to determine several timing characteristics. Results: The average portal time per target dose was 172.5 s/Gy for protons and 150.7 s/Gy for carbon ions. The maximum delivery time for any portal was less than 300 s. The average dwell time per spot was 12 ms for protons and 3.0 ms for carbon ions. The number of aiming positions per energy layer varied from 1 to 258 for protons and 1 to 621 for carbon ions. The average spill time and cycle time per energy layer were 1.20 and 2.68 s for protons and 0.95 and 4.73 s for carbon ions respectively. For 3 of the patients, the beam was gated on and off to reduce the effects of respiration. Conclusion: For a typical target volume of 153 cc as used in this clinical trial, the portal delivery times were acceptable.« less

Distinctive features of "chronotherapeutic" and "pulsatile" drug delivery systems negating the practice of their interchangeable terminology.

PubMed

Ali, Javed; Baboota, Sanjula; Ahuja, Alka; Saigal, Nitin

2010-07-01

The term pulsatile drug delivery has often been used as a synonym to chronotherapeutic drug delivery. This needs to be given a thought as both the drug delivery systems are entirely addressing different needs of the patients as well as the intentions of the formulators being different. Chronotherapeutic systems are based completely on circadian needs and response of the body and the need of the drug to be in its maximum concentrations at a particular time of the day, the fact being supported by endless list of ailments which elicit the related symptoms at a particular time of the day. Considering the formulation approach, one does not find major differences among site-specific chronotherapeutic systems and the basic and more conventional intestinal or colon targeted systems due to the mechanism and the site of landing of drug of both being almost similar even though the intention of the formulator being different. An ideal pulsatile system is the one delivering drug in different pulses with multiple troughs in release profile. The article explores the major differences in between the two systems and highlights the need of using appropriate terminology for these individual and distinct systems catering different needs.

SU-E-T-106: An Institutional Review of Using Commercially Available Software to Evaluate Treatment Plan Quality for Various Treatment Sites and Beam Deliveries

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

Esquivel, C; Patton, L; Walker, S

Purpose: Use Sun Nuclear Quality Reports™ with PlanIQ™ to evaluate different treatment delivery techniques for various treatment sites. Methods: Fifteen random patients with different treatment sites were evaluated. These include the Head/Neck, prostate, pelvis, lung, esophagus, axilla, bladder and abdomen. Initially, these sites were planned on the Pinnacle {sup 3} V9.6 treatment planning system and utilized nine 6MV step-n-shoot IMRT fields. The RT plan, dose and structure sets were sent to Quality Reports™ where a DVH was recreated and the plans were compared to a unique Plan Algorithm for each treatment site. Each algorithm has its own plan quality metricsmore » and objectives, which include the PTV coverage, PTV maximum dose, the prescription dose outside the target, doses to the critical structures, and the global maximum dose and its location. Each plan was scored base on meeting each objective. Plans may have been reoptimized and reevaluated with Quality Reports™ based on the initial score. PlanIQ™ was used to evaluate if any objective not met was achievable or difficult to obtain. A second plan using VMAT delivery was created for each patient and scored with Quality Reports™. Results: There were a wide range of scores for the different treatment sites with some scoring better for IMRT plans and some better for the VMAT deliveries. The variation in the scores could be attributed to the treatment site, location, and shape of the target. Most deliveries were chosen for the VMAT due to the short treatment times and quick patient throughput with acceptable plan scores. Conclusion: The tools are provided for both physician and dosimetrist to objectively evaluate the use of VMAT delivery versus the step-n-shoot IMRT delivery for various sites. PlanIQ validates if objectives can be met. For the physicist, a concise pass/fail report is created for plan evaluation.« less

Current Multistage Drug Delivery Systems Based on the Tumor Microenvironment

PubMed Central

Chen, Binlong; Dai, Wenbing; He, Bing; Zhang, Hua; Wang, Xueqing; Wang, Yiguang; Zhang, Qiang

2017-01-01

The development of traditional tumor-targeted drug delivery systems based on EPR effect and receptor-mediated endocytosis is very challenging probably because of the biological complexity of tumors as well as the limitations in the design of the functional nano-sized delivery systems. Recently, multistage drug delivery systems (Ms-DDS) triggered by various specific tumor microenvironment stimuli have emerged for tumor therapy and imaging. In response to the differences in the physiological blood circulation, tumor microenvironment, and intracellular environment, Ms-DDS can change their physicochemical properties (such as size, hydrophobicity, or zeta potential) to achieve deeper tumor penetration, enhanced cellular uptake, timely drug release, as well as effective endosomal escape. Based on these mechanisms, Ms-DDS could deliver maximum quantity of drugs to the therapeutic targets including tumor tissues, cells, and subcellular organelles and eventually exhibit the highest therapeutic efficacy. In this review, we expatiate on various responsive modes triggered by the tumor microenvironment stimuli, introduce recent advances in multistage nanoparticle systems, especially the multi-stimuli responsive delivery systems, and discuss their functions, effects, and prospects. PMID:28255348

Current Multistage Drug Delivery Systems Based on the Tumor Microenvironment.

PubMed

Chen, Binlong; Dai, Wenbing; He, Bing; Zhang, Hua; Wang, Xueqing; Wang, Yiguang; Zhang, Qiang

2017-01-01

The development of traditional tumor-targeted drug delivery systems based on EPR effect and receptor-mediated endocytosis is very challenging probably because of the biological complexity of tumors as well as the limitations in the design of the functional nano-sized delivery systems. Recently, multistage drug delivery systems (Ms-DDS) triggered by various specific tumor microenvironment stimuli have emerged for tumor therapy and imaging. In response to the differences in the physiological blood circulation, tumor microenvironment, and intracellular environment, Ms-DDS can change their physicochemical properties (such as size, hydrophobicity, or zeta potential) to achieve deeper tumor penetration, enhanced cellular uptake, timely drug release, as well as effective endosomal escape. Based on these mechanisms, Ms-DDS could deliver maximum quantity of drugs to the therapeutic targets including tumor tissues, cells, and subcellular organelles and eventually exhibit the highest therapeutic efficacy. In this review, we expatiate on various responsive modes triggered by the tumor microenvironment stimuli, introduce recent advances in multistage nanoparticle systems, especially the multi-stimuli responsive delivery systems, and discuss their functions, effects, and prospects.

MO-FG-202-08: Real-Time Monte Carlo-Based Treatment Dose Reconstruction and Monitoring for Radiotherapy

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

Tian, Z; Shi, F; Gu, X

2016-06-15

Purpose: This proof-of-concept study is to develop a real-time Monte Carlo (MC) based treatment-dose reconstruction and monitoring system for radiotherapy, especially for the treatments with complicated delivery, to catch treatment delivery errors at the earliest possible opportunity and interrupt the treatment only when an unacceptable dosimetric deviation from our expectation occurs. Methods: First an offline scheme is launched to pre-calculate the expected dose from the treatment plan, used as ground truth for real-time monitoring later. Then an online scheme with three concurrent threads is launched while treatment delivering, to reconstruct and monitor the patient dose in a temporally resolved fashionmore » in real-time. Thread T1 acquires machine status every 20 ms to calculate and accumulate fluence map (FM). Once our accumulation threshold is reached, T1 transfers the FM to T2 for dose reconstruction ad starts to accumulate a new FM. A GPU-based MC dose calculation is performed on T2 when MC dose engine is ready and a new FM is available. The reconstructed instantaneous dose is directed to T3 for dose accumulation and real-time visualization. Multiple dose metrics (e.g. maximum and mean dose for targets and organs) are calculated from the current accumulated dose and compared with the pre-calculated expected values. Once the discrepancies go beyond our tolerance, an error message will be send to interrupt the treatment delivery. Results: A VMAT Head-and-neck patient case was used to test the performance of our system. Real-time machine status acquisition was simulated here. The differences between the actual dose metrics and the expected ones were 0.06%–0.36%, indicating an accurate delivery. ∼10Hz frequency of dose reconstruction and monitoring was achieved, with 287.94s online computation time compared to 287.84s treatment delivery time. Conclusion: Our study has demonstrated the feasibility of computing a dose distribution in a temporally resolved fashion in real-time and quantitatively and dosimetrically monitoring the treatment delivery.« less

SU-E-T-197: Helical Cranial-Spinal Treatments with a Linear Accelerator

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

Anderson, J; Bernard, D; Liao, Y

2014-06-01

Purpose: Craniospinal irradiation (CSI) of systemic disease requires a high level of beam intensity modulation to reduce dose to bone marrow and other critical structures. Current helical delivery machines can take 30 minutes or more of beam-on time to complete these treatments. This pilot study aims to test the feasibility of performing helical treatments with a conventional linear accelerator using longitudinal couch travel during multiple gantry revolutions. Methods: The VMAT optimization package of the Eclipse 10.0 treatment planning system was used to optimize pseudo-helical CSI plans of 5 clinical patient scans. Each gantry revolution was divided into three 120° arcsmore » with each isocenter shifted longitudinally. Treatments requiring more than the maximum 10 arcs used multiple plans with each plan after the first being optimized including the dose of the others (Figure 1). The beam pitch was varied between 0.2 and 0.9 (couch speed 5- 20cm/revolution and field width of 22cm) and dose-volume histograms of critical organs were compared to tomotherapy plans. Results: Viable pseudo-helical plans were achieved using Eclipse. Decreasing the pitch from 0.9 to 0.2 lowered the maximum lens dose by 40%, the mean bone marrow dose by 2.1% and the maximum esophagus dose by 17.5%. (Figure 2). Linac-based helical plans showed dose results comparable to tomotherapy delivery for both target coverage and critical organ sparing, with the D50 of bone marrow and esophagus respectively 12% and 31% lower in the helical linear accelerator plan (Figure 3). Total mean beam-on time for the linear accelerator plan was 8.3 minutes, 54% faster than the tomotherapy average for the same plans. Conclusions: This pilot study has demonstrated the feasibility of planning pseudo-helical treatments for CSI targets using a conventional linac and dynamic couch movement, and supports the ongoing development of true helical optimization and delivery.« less

Qualification of a sublimation tool applied to the case of metalorganic chemical vapor deposition of In{sub 2}O{sub 3} from In(tmhd){sub 3} as a solid precursor

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

Szkutnik, P. D., E-mail: pierre.szkutnik@cea.fr; Jiménez, C.; Angélidès, L.

2016-02-15

A solid delivery system consisting of a source canister, a gas management, and temperature controlled enclosure designed and manufactured by Air Liquide Electronics Systems was tested in the context of gas-phase delivery of the In(tmhd){sub 3} solid precursor. The precursor stream was delivered to a thermal metalorganic chemical vapor deposition reactor to quantify deposition yield under various conditions of carrier gas flow and sublimation temperature. The data collected allowed the determination of characteristic parameters such as the maximum precursor flow rate (18.2 mg min{sup −1} in specified conditions) and the critical mass (defined as the minimum amount of precursor ablemore » to attain the maximum flow rate) found to be about 2.4 g, as well as an understanding of the influence of powder distribution inside the canister. Furthermore, this qualification enabled the determination of optimal delivery conditions which allowed for stable and reproducible precursor flow rates over long deposition times (equivalent to more than 47 h of experiment). The resulting In{sub 2}O{sub 3} layers was compared with those elaborated via pulsed liquid injection obtained in the same chemical vapor deposition chamber and under the same deposition conditions.« less

Design of a multifiber light delivery system for photoacoustic-guided surgery.

PubMed

Eddins, Blackberrie; Bell, Muyinatu A Lediju

2017-04-01

This work explores light delivery optimization for photoacoustic-guided minimally invasive surgeries, such as the endonasal transsphenoidal approach. Monte Carlo simulations were employed to study three-dimensional light propagation in tissue, comprising one or two 4-mm diameter arteries located 3 mm below bone, an absorbing metallic drill contacting the bone surface, and a single light source placed next to the 2.4-mm diameter drill shaft with a 2.9-mm diameter spherical drill tip. The optimal fiber distance from the drill shaft was determined from the maximum normalized fluence to the underlying artery. Using this optimal fiber-to-drill shaft distance, Zemax simulations were employed to propagate Gaussian beams through one or more 600 micron-core diameter optical fibers for detection on the bone surface. When the number of equally spaced fibers surrounding the drill increased, a single merged optical profile formed with seven or more fibers, determined by thresholding the resulting light profile images at 1 / e times the maximum intensity. We used these simulations to inform design requirements, build a one to seven multifiber light delivery prototype to surround a surgical drill, and demonstrate its ability to simultaneously visualize the tool tip and blood vessel targets in the absence and presence of bone. The results and methodology are generalizable to multiple interventional photoacoustic applications.

Design of a multifiber light delivery system for photoacoustic-guided surgery

NASA Astrophysics Data System (ADS)

Eddins, Blackberrie; Bell, Muyinatu A. Lediju

2017-04-01

This work explores light delivery optimization for photoacoustic-guided minimally invasive surgeries, such as the endonasal transsphenoidal approach. Monte Carlo simulations were employed to study three-dimensional light propagation in tissue, comprising one or two 4-mm diameter arteries located 3 mm below bone, an absorbing metallic drill contacting the bone surface, and a single light source placed next to the 2.4-mm diameter drill shaft with a 2.9-mm diameter spherical drill tip. The optimal fiber distance from the drill shaft was determined from the maximum normalized fluence to the underlying artery. Using this optimal fiber-to-drill shaft distance, Zemax simulations were employed to propagate Gaussian beams through one or more 600 micron-core diameter optical fibers for detection on the bone surface. When the number of equally spaced fibers surrounding the drill increased, a single merged optical profile formed with seven or more fibers, determined by thresholding the resulting light profile images at 1/e times the maximum intensity. We used these simulations to inform design requirements, build a one to seven multifiber light delivery prototype to surround a surgical drill, and demonstrate its ability to simultaneously visualize the tool tip and blood vessel targets in the absence and presence of bone. The results and methodology are generalizable to multiple interventional photoacoustic applications.

Installation Restoration Program. Site Investigation Report. Volume 1. 152nd Tactical Reconnaissance Group, Nevada Air National Guard, Reno Cannon International Airport, Reno, Nevada

DTIC Science & Technology

1994-04-01

measure RRI - Rapid Response Initiative RT - retention time s - seconds SDG - sample delivery group I SI - site investigation SMCLS - secondary maximum...tape and a compass and each grid node was marked with a wooden stake or fluorescent orange paint. At least one point on the grid was surveyed so the

The safety and pharmacokinetics of rapid iloprost aerosol delivery via the BREELIB nebulizer in pulmonary arterial hypertension

PubMed Central

Gessler, Tobias; Ghofrani, Hossein-Ardeschir; Held, Matthias; Klose, Hans; Leuchte, Hanno; Olschewski, Horst; Rosenkranz, Stephan; Fels, Lueder; Li, Na; Ren, Dawn; Kaiser, Andreas; Schultze-Mosgau, Marcus-Hillert; Müllinger, Bernhard; Rohde, Beate; Seeger, Werner

2017-01-01

The BREELIB nebulizer was developed for iloprost to reduce inhalation times for patients with pulmonary arterial hypertension (PAH). This multicenter, randomized, unblinded, four-part study compared inhalation time, pharmacokinetics, and acute tolerability of iloprost 5 µg at mouthpiece delivered via BREELIB versus the standard I-Neb nebulizer in 27 patients with PAH. The primary safety outcome was the proportion of patients with a maximum increase in heart rate (HR) ≥ 25% and/or a maximum decrease in systolic blood pressure ≥ 20% within 30 min after inhalation. Other safety outcomes included systolic, diastolic, and mean blood pressure, HR, oxygen saturation, and adverse events (AEs). Median inhalation times were considerably shorter with BREELIB versus I-Neb (2.6 versus 10.9 min; n = 24). Maximum iloprost plasma concentration and systemic exposure (area under the plasma concentration–time curve) were 77% and 42% higher, respectively, with BREELIB versus I-Neb. Five patients experienced a maximum systolic blood pressure decrease ≥ 20%, four with BREELIB (one mildly and transiently symptomatic), and one with I-Neb; none required medical intervention. AEs reported during the study were consistent with the known safety profile of iloprost. The BREELIB nebulizer offers reduced inhalation time, good tolerability, and may improve iloprost aerosol therapy convenience and thus compliance for patients with PAH. PMID:28597762

Type of delivery and gestational age is not affected by pregnant Latin-American women engaging in vigorous exercise: a secondary analysis of data from a controlled randomized trial.

PubMed

Pinzón, Diana C; Zamora, Katherine; Martínez, Jorge H; Floréz-López, María E; de Plata, Ana C Aguilar; Mosquera, Mildrey; Ramírez-Vélez, Robinson

2012-10-01

There is controversy concerning whether exercise during pregnancy may increase preterm delivery risk and type of delivery. The effect of pregnant Latin-American women engaging in vigorous exercise during the second and third trimester was examined regarding type of delivery and gestational age. This was a secondary analysis of data from a controlled randomized trial for determining the influence of physical exercise on pregnant women's endothelial function. The study included 35 nulliparous women, gestational week 16-20 attending prenatal care at three tertiary hospitals in Colombia, who were randomly assigned to one of two groups. The experimental group engaged in aerobic exercise involving 55 % - 75 % maximum heart rate for 60 min, three times a week for 12 weeks. The control group engaged in their usual physical activity. Maternal weight, height, weight gain, blood pressure and type of delivery were recorded; gender, abdominal and head circumference (cm), weight (g), height (cm), vitality (Apgar score at 1 and 5 min) and gestational age at the time of delivery (in weeks, days) were recorded for the newborn. There was no difference in type of delivery by the end of the 12-week program (p > 0.05), nor regarding newborn anthropometric variables, Apgar score, or maternal variables concerning weight, height, relative weight gain, blood pressure or weeks of gestation (p>0.05). The potential public health benefits of vigorous exercise were enormous. This study supported existing guidelines indicating that Latin-American women may begin or maintain an on-going exercise program during pregnancy. NCT00741312.

Compensators: An alternative IMRT delivery technique

PubMed Central

Chang, Sha X.; Cullip, Timothy J.; Deschesne, Katharin M.; Miller, Elizabeth P.; Rosenman, Julian G.

2004-01-01

Seven years of experience in compensator intensity‐modulated radiotherapy (IMRT) clinical implementation are presented. An inverse planning dose optimization algorithm was used to generate intensity modulation maps, which were delivered via either the compensator or segmental multileaf collimator (MLC) IMRT techniques. The in‐house developed compensator‐IMRT technique is presented with the focus on several design issues. The dosimetry of the delivery techniques was analyzed for several clinical cases. The treatment time for both delivery techniques on Siemens accelerators was retrospectively analyzed based on the electronic treatment record in LANTIS for 95 patients. We found that the compensator technique consistently took noticeably less time for treatment of equal numbers of fields compared to the segmental technique. The typical time needed to fabricate a compensator was 13 min, 3 min of which was manual processing. More than 80% of the approximately 700 compensators evaluated had a maximum deviation of less than 5% from the calculation in intensity profile. Seventy‐two percent of the patient treatment dosimetry measurements for 340 patients have an error of no more than 5%. The pros and cons of different IMRT compensator materials are also discussed. Our experience shows that the compensator‐IMRT technique offers robustness, excellent intensity modulation resolution, high treatment delivery efficiency, simple fabrication and quality assurance (QA) procedures, and the flexibility to be used in any teletherapy unit. PACS numbers: 87.53Mr, 87.53Tf PMID:15753937

Pelvic floor muscle exercise by biofeedback and electrical stimulation to reinforce the pelvic floor muscle after normal delivery.

PubMed

Lee, In Sook; Choi, Euy Soon

2006-12-01

This study was conducted to investigate the effectiveness of pelvic floor muscle exercise using biofeedback and electrical stimulation after normal delivery. The subjects of this study were 49 (experimental group: 25, control group: 24) postpartum women who passed 6 weeks after normal delivery without complication of pregnancy, delivery and postpartum. The experimental group was applied to the pelvic muscle enforcement program by biofeedback and electrical stimulation for 30 minutes per session, twice a week for 6 weeks, after then self-exercise of pelvic floor muscle was done 50-60 repetition per session, 3 times a day for 6 weeks. Maximum pressure of pelvic floor muscle contraction (MPPFMC), average pressure of pelvic floor muscle contraction (APPFMC), duration time of pelvic floor muscle contraction (DTPFMC) and the subjective lower urinary symptoms were measured by digital perineometer and Bristol Female Urinary Symptom Questionnaire and compared between two groups prior to trial, at the end of treatment and 6 weeks after treatment. The results of this study indicated that MPPFMC, APPFMC, DTPFMC were significantly increased and subjective lower urinary symptoms were significantly decreased after treatment in the experimental group than in the control group. This study suggested that the pelvic floor muscle exercise using biofeedback and electrical stimulation might be a safer and more effective program for reinforcing pelvic floor muscle after normal delivery.

Preliminary pharmacology of galactosylated chitosan/5-fluorouracil nanoparticles and its inhibition of hepatocellular carcinoma in mice

PubMed Central

Cheng, Mingrong; Liu, Zheng; Wan, Tao; He, Bing; Zha, Bingbing; Han, Jiang; Chen, Houxiang; Yang, Fengxiao; Li, Qing; Wang, Wei; Xu, Hongzhi; Ye, Tao

2012-01-01

Biodegradable polymer nanoparticle drug delivery systems are characterized by targeted drug delivery, improved pharmacokinetic and biodistribution, enhanced drug stability and lowered side effects; these drug delivery systems are widely used for delivery of cytotoxic agents. The galactosylated chitosan (GC)/5-fluorouracil (5-FU) nanoparticle is a nanomaterial made by coupling GC, a polymer known to have the advantages described above, and 5-FU. The GC/5-FU nanoparticle is a sustained release system, it was showed that the peak time, half-life time, mean residence time (MRT) and area of under curve (AUC) of GC/5-FU were longer or more than those of the 5-FU group, but the maximum concentration (Cmax) was lower. The distribution of GC/5-FU in vivo revealed the greatest accumulation in the hepatic cancer tissues, and the hepatic cell was the target of the nanoparticles. Toxicology research showed that the toxicity of GC-5-FU was lower than that of 5-FU in mice. In vivo experiments showed that GC/5-FU can significantly inhibit tumor growth in an orthotropic liver cancer mouse model. GC/5-FU treatment can significantly lower the tumor weight and increase the survival time of mice when compared with 5-FU treatment alone. Flow cytometry and the TUNEL assay revealed that compared with 5-FU, GC/5-FU caused higher rates of G0-G1 arrest and apoptosis in hepatic cancer cells. PMID:22954702

Low-Radiation Cellular Inductive Powering of Rodent Wireless Brain Interfaces: Methodology and Design Guide.

PubMed

Soltani, Nima; Aliroteh, Miaad S; Salam, M Tariqus; Perez Velazquez, Jose Luis; Genov, Roman

2016-08-01

This paper presents a general methodology of inductive power delivery in wireless chronic rodent electrophysiology applications. The focus is on such systems design considerations under the following key constraints: maximum power delivery under the allowable specific absorption rate (SAR), low cost and spatial scalability. The methodology includes inductive coil design considerations within a low-frequency ferrite-core-free power transfer link which includes a scalable coil-array power transmitter floor and a single-coil implanted or worn power receiver. A specific design example is presented that includes the concept of low-SAR cellular single-transmitter-coil powering through dynamic tracking of a magnet-less receiver spatial location. The transmitter coil instantaneous supply current is monitored using a small number of low-cost electronic components. A drop in its value indicates the proximity of the receiver due to the reflected impedance of the latter. Only the transmitter coil nearest to the receiver is activated. Operating at the low frequency of 1.5 MHz, the inductive powering floor delivers a maximum of 15.9 W below the IEEE C95 SAR limit, which is over three times greater than that in other recently reported designs. The power transfer efficiency of 39% and 13% at the nominal and maximum distances of 8 cm and 11 cm, respectively, is maintained.

Guaranteed epsilon-optimal treatment plans with the minimum number of beams for stereotactic body radiation therapy

NASA Astrophysics Data System (ADS)

Yarmand, Hamed; Winey, Brian; Craft, David

2013-09-01

Stereotactic body radiation therapy (SBRT) is characterized by delivering a high amount of dose in a short period of time. In SBRT the dose is delivered using open fields (e.g., beam’s-eye-view) known as ‘apertures’. Mathematical methods can be used for optimizing treatment planning for delivery of sufficient dose to the cancerous cells while keeping the dose to surrounding organs at risk (OARs) minimal. Two important elements of a treatment plan are quality and delivery time. Quality of a plan is measured based on the target coverage and dose to OARs. Delivery time heavily depends on the number of beams used in the plan as the setup times for different beam directions constitute a large portion of the delivery time. Therefore the ideal plan, in which all potential beams can be used, will be associated with a long impractical delivery time. We use the dose to OARs in the ideal plan to find the plan with the minimum number of beams which is guaranteed to be epsilon-optimal (i.e., a predetermined maximum deviation from the ideal plan is guaranteed). Since the treatment plan optimization is inherently a multi-criteria-optimization problem, the planner can navigate the ideal dose distribution Pareto surface and select a plan of desired target coverage versus OARs sparing, and then use the proposed technique to reduce the number of beams while guaranteeing epsilon-optimality. We use mixed integer programming (MIP) for optimization. To reduce the computation time for the resultant MIP, we use two heuristics: a beam elimination scheme and a family of heuristic cuts, known as ‘neighbor cuts’, based on the concept of ‘adjacent beams’. We show the effectiveness of the proposed technique on two clinical cases, a liver and a lung case. Based on our technique we propose an algorithm for fast generation of epsilon-optimal plans.

Delivery of high energy Er:YAG pulsed laser light at 2.94 µm through a silica hollow core photonic crystal fibre.

PubMed

Urich, A; Maier, R R J; Mangan, B J; Renshaw, S; Knight, J C; Hand, D P; Shephard, J D

2012-03-12

In this paper the delivery of high power Er:YAG laser pulses through a silica hollow core photonic crystal fibre is demonstrated. The Er:YAG wavelength of 2.94 µm is well beyond the normal transmittance of bulk silica but the unique hollow core guidance allows silica to guide in this regime. We have demonstrated for the first time the ability to deliver high energy pulses through an all-silica fibre at 2.94 µm. These silica fibres are mechanically and chemically robust, biocompatible and have low sensitivity to bending. A maximum pulse energy of 14 mJ at 2.94 µm was delivered through the fibre. This, to our knowledge, is the first time a silica hollow core photonic crystal fibre has been shown to transmit 2.94 μm laser light at a fluence exceeding the thresholds required for modification (e.g. cutting and drilling) of hard biological tissue. Consequently, laser delivery systems based on these fibres have the potential for the realization of novel, minimally-invasive surgical procedures.

Efficient packet transportation on complex networks with nonuniform node capacity distribution

NASA Astrophysics Data System (ADS)

He, Xuan; Niu, Kai; He, Zhiqiang; Lin, Jiaru; Jiang, Zhong-Yuan

2015-03-01

Provided that node delivery capacity may be not uniformly distributed in many realistic networks, we present a node delivery capacity distribution in which each node capacity is composed of uniform fraction and degree related proportion. Based on the node delivery capacity distribution, we construct a novel routing mechanism called efficient weighted routing (EWR) strategy to enhance network traffic capacity and transportation efficiency. Compared with the shortest path routing and the efficient routing strategies, the EWR achieves the highest traffic capacity. After investigating average path length, network diameter, maximum efficient betweenness, average efficient betweenness, average travel time and average traffic load under extensive simulations, it indicates that the EWR appears to be a very effective routing method. The idea of this routing mechanism gives us a good insight into network science research. The practical use of this work is prospective in some real complex systems such as the Internet.

Geometric Verification of Dynamic Wave Arc Delivery With the Vero System Using Orthogonal X-ray Fluoroscopic Imaging.

PubMed

Burghelea, Manuela; Verellen, Dirk; Poels, Kenneth; Gevaert, Thierry; Depuydt, Tom; Tournel, Koen; Hung, Cecilia; Simon, Viorica; Hiraoka, Masahiro; de Ridder, Mark

2015-07-15

The purpose of this study was to define an independent verification method based on on-board orthogonal fluoroscopy to determine the geometric accuracy of synchronized gantry-ring (G/R) rotations during dynamic wave arc (DWA) delivery available on the Vero system. A verification method for DWA was developed to calculate O-ring-gantry (G/R) positional information from ball-bearing positions retrieved from fluoroscopic images of a cubic phantom acquired during DWA delivery. Different noncoplanar trajectories were generated in order to investigate the influence of path complexity on delivery accuracy. The G/R positions detected from the fluoroscopy images (DetPositions) were benchmarked against the G/R angulations retrieved from the control points (CP) of the DWA RT plan and the DWA log files recorded by the treatment console during DWA delivery (LogActed). The G/R rotational accuracy was quantified as the mean absolute deviation ± standard deviation. The maximum G/R absolute deviation was calculated as the maximum 3-dimensional distance between the CP and the closest DetPositions. In the CP versus DetPositions comparison, an overall mean G/R deviation of 0.13°/0.16° ± 0.16°/0.16° was obtained, with a maximum G/R deviation of 0.6°/0.2°. For the LogActed versus DetPositions evaluation, the overall mean deviation was 0.08°/0.15° ± 0.10°/0.10° with a maximum G/R of 0.3°/0.4°. The largest decoupled deviations registered for gantry and ring were 0.6° and 0.4° respectively. No directional dependence was observed between clockwise and counterclockwise rotations. Doubling the dose resulted in a double number of detected points around each CP, and an angular deviation reduction in all cases. An independent geometric quality assurance approach was developed for DWA delivery verification and was successfully applied on diverse trajectories. Results showed that the Vero system is capable of following complex G/R trajectories with maximum deviations during DWA below 0.6°. Copyright © 2015 Elsevier Inc. All rights reserved.

Ramped-rate vs continuous-rate infusions: An in vitro comparison of convection enhanced delivery protocols.

PubMed

Schomberg, Dominic; Wang, Anyi; Marshall, Hope; Miranpuri, Gurwattan; Sillay, Karl

2013-04-01

Convection enhanced delivery (CED) is a technique using infusion convection currents to deliver therapeutic agents into targeted regions of the brain. Recently, CED is gaining significant acceptance for use in gene therapy of Parkinson's disease (PD) employing direct infusion into the brain. CED offers advantages in that it targets local areas of the brain, bypasses the blood-brain barrier (BBB), minimizes systemic toxicity of the therapeutics, and allows for delivery of larger molecules that diffusion driven methods cannot achieve. Investigating infusion characteristics such as backflow and morphology is important in developing standard and effective protocols in order to successfully deliver treatments into the brain. Optimizing clinical infusion protocols may reduce backflow, improve final infusion cloud morphology, and maximize infusate penetrance into targeted tissue. The purpose of the current study was to compare metrics during ramped-rate and continuous-rate infusions using two different catheters in order to optimize current infusion protocols. Occasionally, the infusate refluxes proximally up the catheter tip, known as backflow, and minimizing this can potentially reduce undesirable effects in the clinical setting. Traditionally, infusions are performed at a constant rate throughout the entire duration, and backflow is minimized only by slow infusion rates, which increases the time required to deliver the desired amount of infusate. In this study, we investigate the effects of ramping and various infusion rates on backflow and infusion cloud morphology. The independent parameters in the study are: ramping, maximum infusion rate, time between rate changes, and increments of rate changes. Backflow was measured using two methods: i) at the point of pressure stabilization within the catheter, and ii) maximum backflow as shown by video data. Infusion cloud morphology was evaluated based on the height-to-width ratio of each infusion cloud at the end of each experiment. Results were tabulated and statistically analyzed to identify any significant differences between protocols. The experimental results show that CED rampedrate infusion protocols result in smaller backflow distances and more spherical cloud morphologies compared to continuous-rate infusion protocols ending at the same maximum infusion rate. Our results also suggest internal-line pressure measurements can approximate the time-point at which backflow ceases. Our findings indicate that ramping CED infusion protocols can potentially minimize backflow and produce more spherical infusion clouds. However, further research is required to determine the strength of this correlation, especially in relation to maximum infusion rates.

Fabrication of core-shell nanofibers for controlled delivery of bromelain and salvianolic acid B for skin regeneration in wound therapeutics.

PubMed

Shoba, Ekambaram; Lakra, Rachita; Syamala Kiran, Manikantan; Korrapati, Purna Sai

2017-06-05

The physiological and pathological complexity of the wound healing process makes it more challenging to design an ideal tissue regeneration scaffold. Precise scaffolding with high drug loading efficiency, efficient intracellular efficacy for therapeutic delivery, minimal nonspecific cellular and blood protein binding, and maximum biocompatibility forms the basis for an ideal delivery system. This paper describes a combinational multiphasic delivery system, where biomolecules are delivered through the fabrication of coaxial electrospinning of different biocompatible polymers. The ratio and specificity of polymers for specific biofunction are optimized and the delivery system is completely characterized with reference to the mechanical property and structural integrity of bromelain (debridement enzyme) and salvianolic acid B (pro-angiogenesis and re-epithelialization). The in vitro release profile illustrated the sustained release of debriding protease and bioactive component in a timely fashion. The fabricated scaffold showed angiogenic potential through in vitro migration of endothelial cells and increased new capillaries from the existing blood vessel in response to an in ovo chicken chorioallantoic membrane assay. In addition, in vivo studies confirm the efficacy of the fabricated scaffold. Our results therefore open up a new avenue for designing a bioactive combinational multiphasic delivery system to enhance wound healing.

SU-F-T-435: Helical Tomotherapy for Craniospinal Irradiation: What We Have Learned from a Multi-Institutional Study

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

Du, D; Kaprealian, T; Low, D

Purpose: To report cranio-spinal irradiation (CSI) planning experience, compare dosimetric quality and delivery efficiency with Tomotherapy from different institutions, and to investigate effect of planning parameters on plan quality and treatment time. Methods: Clinical helical tomotherapy IMRT plans for thirty-nine CSI cases from three academic institutions were retrospectively evaluated. The planning parameters: field width (FW), pitch, modulation factor (MF), and achieved dosimetric endpoints were cross-compared. A fraction-dose-delivery-timing index (FDTI), defined as treatment time per fraction dose per PTV length, was utilized to evaluate plan delivery efficiency. A lower FDTI indicates higher delivery efficiency. We studied the correlation between planning quality,more » treatment time and planning parameters by grouping the plans under specific planning parameters. Additionally, we created new plans using 5cm jaw for a subset of plans that used 2.5cm jaw to exam if treatment efficiency can be improved without sacrificing plan quality. Results: There were significant dosimetric differences for organ at risks (OARs) among different institutions (A,B,C). Using the lowest average MF (1.9±0.4) and 5cm field width, C had the highest lung, heart, kidney, liver mean doses and maximum doses for lens. Using the same field width of 5cm, but higher MF (2.6±0.6), B had lower doses to the OARs in the thorax and abdomen area. Most of A’s plans were planned with 2.5cm jaw, the plans yielded better PTV coverage, higher OAR doses and slightly shorter FDTI compared to institution B. The replanned 5cm jaw plans achieved comparable PTV coverage and OARs sparing, while saving up to 44.7% treatment time. Conclusion: Plan quality and delivery efficiency could vary significantly in CSI planning on Tomotheapy due to choice of different planning parameters. CSI plans using a 5cm jaw, with proper selection of pitch and MF, can achieve comparable/ better plan quality with shorter delivery time compared to 2.5cm jaw plans.« less

Modeling Food Delivery Dynamics For Juvenile Salmonids Under Variable Flow Regimes

NASA Astrophysics Data System (ADS)

Harrison, L.; Utz, R.; Anderson, K.; Nisbet, R.

2010-12-01

Traditional approaches for assessing instream flow needs for salmonids have typically focused on the importance of physical habitat in determining fish habitat selection. This somewhat simplistic approach does not account for differences in food delivery rates to salmonids that arise due to spatial variability in river morphology, hydraulics and temporal variations in the flow regime. Explicitly linking how changes in the flow regime influences food delivery dynamics is an important step in advancing process-based bioenergetic models that seek to predict growth rates of salmonids across various life-stages. Here we investigate how food delivery rates for juvenile salmonids vary both spatially and with flow magnitude in a meandering reach of the Merced River, CA. We utilize a two-dimensional (2D) hydrodynamic model and discrete particle tracking algorithm to simulate invertebrate drift transport rates at baseflow and a near-bankfull discharge. Modeling results indicate that at baseflow, the maximum drift density occurs in the channel thalweg, while drift densities decrease towards the channel margins due to the process of organisms settling out of the drift. During high-flow events, typical of spring dam-releases, the invertebrate drift transport pathway follows a similar trajectory along the high velocity core and the drift concentrations are greatest in the channel centerline, though the zone of invertebrate transport occupies a greater fraction of the channel width. Based on invertebrate supply rates alone, feeding juvenile salmonids would be expected to be distributed down the channel centerline where the maximum predicted food delivery rates are located in this reach. However, flow velocities in these channel sections are beyond maximum sustainable swimming speeds for most juvenile salmonids. Our preliminary findings suggest that a lack of low velocity refuge may prevent juvenile salmonids from deriving energy from the areas with maximum drift density in this reach. Future efforts will focus on integration of food delivery and bioenergetic models to account for conflicting demands of maximizing food intake while minimizing the energetic costs of swimming.

Technical aspects of real time positron emission tracking for gated radiotherapy

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

Chamberland, Marc; Xu, Tong, E-mail: txu@physics.carleton.ca; McEwen, Malcolm R.

2016-02-15

Purpose: Respiratory motion can lead to treatment errors in the delivery of radiotherapy treatments. Respiratory gating can assist in better conforming the beam delivery to the target volume. We present a study of the technical aspects of a real time positron emission tracking system for potential use in gated radiotherapy. Methods: The tracking system, called PeTrack, uses implanted positron emission markers and position sensitive gamma ray detectors to track breathing motion in real time. PeTrack uses an expectation–maximization algorithm to track the motion of fiducial markers. A normalized least mean squares adaptive filter predicts the location of the markers amore » short time ahead to account for system response latency. The precision and data collection efficiency of a prototype PeTrack system were measured under conditions simulating gated radiotherapy. The lung insert of a thorax phantom was translated in the inferior–superior direction with regular sinusoidal motion and simulated patient breathing motion (maximum amplitude of motion ±10 mm, period 4 s). The system tracked the motion of a {sup 22}Na fiducial marker (0.34 MBq) embedded in the lung insert every 0.2 s. The position of the was marker was predicted 0.2 s ahead. For sinusoidal motion, the equation used to model the motion was fitted to the data. The precision of the tracking was estimated as the standard deviation of the residuals. Software was also developed to communicate with a Linac and toggle beam delivery. In a separate experiment involving a Linac, 500 monitor units of radiation were delivered to the phantom with a 3 × 3 cm photon beam and with 6 and 10 MV accelerating potential. Radiochromic films were inserted in the phantom to measure spatial dose distribution. In this experiment, the period of motion was set to 60 s to account for beam turn-on latency. The beam was turned off when the marker moved outside of a 5-mm gating window. Results: The precision of the tracking in the IS direction was 0.53 mm for a sinusoidally moving target, with an average count rate ∼250 cps. The average prediction error was 1.1 ± 0.6 mm when the marker moved according to irregular patient breathing motion. Across all beam deliveries during the radiochromic film measurements, the average prediction error was 0.8 ± 0.5 mm. The maximum error was 2.5 mm and the 95th percentile error was 1.5 mm. Clear improvement of the dose distribution was observed between gated and nongated deliveries. The full-width at halfmaximum of the dose profiles of gated deliveries differed by 3 mm or less than the static reference dose distribution. Monitoring of the beam on/off times showed synchronization with the location of the marker within the latency of the system. Conclusions: PeTrack can track the motion of internal fiducial positron emission markers with submillimeter precision. The system can be used to gate the delivery of a Linac beam based on the position of a moving fiducial marker. This highlights the potential of the system for use in respiratory-gated radiotherapy.« less

Skin permeability enhancement by Bacillus subtilis alkaline protease: Application to transdermal drug delivery.

PubMed

Nounou, Mohamed I; Zaghloul, Taha I; Ahmed, Nehal A; Eid, Amira A; El-Khordagui, Labiba K

2017-08-30

Enzymes may offer great potentials in topical pharmaceutical applications provided that treatment conditions are controlled for efficacy and safety. In this study, the effect of alkaline protease produced by recombinant Bacillus subtilis cells on the ex-vivo permeability of rabbit ear skin was investigated under different conditions of enzyme activity (5-60 units) and exposure time (15-60min). Data for transepidermal water loss (TEWL) and permeation of a hydrophilic dye, rhodamine B (Rb), indicated biphasic activity-dependent and exposure time-dependent skin permeability. Maximum effects were obtained at 20 proteolytic units and 30min exposure. Findings proved consistent with histopathological changes indicating progressive stratum corneum (SC) loss and disruption of the dermo-epidermal junction at 20 units and up to 30min exposure time followed by dermal hyalinization at longer exposure. This was associated with progressive loss of skin hair. Applying the identified pretreatment conditions to transdermal delivery of vardenafil in a gel base across dorsal rat skin indicated a significant increase in plasma levels at 30 and 60min with minimal histopathological changes 5days post enzyme treatment. Accordingly, the recombinant B. subtilis alkaline protease offers promise as a pharmaceutical enzyme for transdermal drug delivery bioenhancement and dermatological applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Volumetric‐modulated arc therapy planning using multicriteria optimization for localized prostate cancer

PubMed Central

Ghandour, Sarah; Matzinger, Oscar

2015-01-01

The purpose of this work is to evaluate the volumetric‐modulated arc therapy (VMAT) multicriteria optimization (MCO) algorithm clinically available in the RayStation treatment planning system (TPS) and its ability to reduce treatment planning time while providing high dosimetric plan quality. Nine patients with localized prostate cancer who were previously treated with 78 Gy in 39 fractions using VMAT plans and rayArc system based on the direct machine parameter optimization (DMPO) algorithm were selected and replanned using the VMAT‐MCO system. First, the dosimetric quality of the plans was evaluated using multiple conformity metrics that account for target coverage and sparing of healthy tissue, used in our departmental clinical protocols. The conformity and homogeneity index, number of monitor units, and treatment planning time for both modalities were assessed. Next, the effects of the technical plan parameters, such as constraint leaf motion CLM (cm/°) and maximum arc delivery time T (s), on the accuracy of delivered dose were evaluated using quality assurance passing rates (QAs) measured using the Delta4 phantom from ScandiDos. For the dosimetric plan's quality analysis, the results show that the VMAT‐MCO system provides plans comparable to the rayArc system with no statistical difference for V95% (p<0.01), D1% (p<0.01), CI (p<0.01), and HI (p<0.01) of the PTV, bladder (p<0.01), and rectum (p<0.01) constraints, except for the femoral heads and healthy tissues, for which a dose reduction was observed using MCO compared with rayArc (p<0.01). The technical parameter study showed that a combination of CLM equal to 0.5 cm/degree and a maximum delivery time of 72 s allowed the accurate delivery of the VMAT‐MCO plan on the Elekta Versa HD linear accelerator. Planning evaluation and dosimetric measurements showed that VMAT‐MCO can be used clinically with the advantage of enhanced planning process efficiency by reducing the treatment planning time without impairing dosimetric quality. PACS numbers: 87.55.D, 87.55.de, 87.55.Qr PMID:26103500

Evaluating the efficacies of Maximum Tolerated Dose and metronomic chemotherapies: A mathematical approach

NASA Astrophysics Data System (ADS)

Guiraldello, Rafael T.; Martins, Marcelo L.; Mancera, Paulo F. A.

2016-08-01

We present a mathematical model based on partial differential equations that is applied to understand tumor development and its response to chemotherapy. Our primary aim is to evaluate comparatively the efficacies of two chemotherapeutic protocols, Maximum Tolerated Dose (MTD) and metronomic, as well as two methods of drug delivery. Concerning therapeutic outcomes, the metronomic protocol proves more effective in prolonging the patient's life than MTD. Moreover, a uniform drug delivery method combined with the metronomic protocol is the most efficient strategy to reduce tumor density.

Determination of prospective displacement-based gate threshold for respiratory-gated radiation delivery from retrospective phase-based gate threshold selected at 4D CT simulation.

PubMed

Vedam, S; Archambault, L; Starkschall, G; Mohan, R; Beddar, S

2007-11-01

Four-dimensional (4D) computed tomography (CT) imaging has found increasing importance in the localization of tumor and surrounding normal structures throughout the respiratory cycle. Based on such tumor motion information, it is possible to identify the appropriate phase interval for respiratory gated treatment planning and delivery. Such a gating phase interval is determined retrospectively based on tumor motion from internal tumor displacement. However, respiratory-gated treatment is delivered prospectively based on motion determined predominantly from an external monitor. Therefore, the simulation gate threshold determined from the retrospective phase interval selected for gating at 4D CT simulation may not correspond to the delivery gate threshold that is determined from the prospective external monitor displacement at treatment delivery. The purpose of the present work is to establish a relationship between the thresholds for respiratory gating determined at CT simulation and treatment delivery, respectively. One hundred fifty external respiratory motion traces, from 90 patients, with and without audio-visual biofeedback, are analyzed. Two respiratory phase intervals, 40%-60% and 30%-70%, are chosen for respiratory gating from the 4D CT-derived tumor motion trajectory. From residual tumor displacements within each such gating phase interval, a simulation gate threshold is defined based on (a) the average and (b) the maximum respiratory displacement within the phase interval. The duty cycle for prospective gated delivery is estimated from the proportion of external monitor displacement data points within both the selected phase interval and the simulation gate threshold. The delivery gate threshold is then determined iteratively to match the above determined duty cycle. The magnitude of the difference between such gate thresholds determined at simulation and treatment delivery is quantified in each case. Phantom motion tests yielded coincidence of simulation and delivery gate thresholds to within 0.3%. For patient data analysis, differences between simulation and delivery gate thresholds are reported as a fraction of the total respiratory motion range. For the smaller phase interval, the differences between simulation and delivery gate thresholds are 8 +/- 11% and 14 +/- 21% with and without audio-visual biofeedback, respectively, when the simulation gate threshold is determined based on the mean respiratory displacement within the 40%-60% gating phase interval. For the longer phase interval, corresponding differences are 4 +/- 7% and 8 +/- 15% with and without audiovisual biofeedback, respectively. Alternatively, when the simulation gate threshold is determined based on the maximum average respiratory displacement within the gating phase interval, greater differences between simulation and delivery gate thresholds are observed. A relationship between retrospective simulation gate threshold and prospective delivery gate threshold for respiratory gating is established and validated for regular and nonregular respiratory motion. Using this relationship, the delivery gate threshold can be reliably estimated at the time of 4D CT simulation, thereby improving the accuracy and efficiency of respiratory-gated radiation delivery.

Formulation and characterization of cetylpyridinium chloride bioadhesive tablets.

PubMed

Akbari, Jafar; Saeedi, Majid; Morteza-Semnani, Katayoun; Kelidari, Hamidreza; Lashkari, Maryam

2014-12-01

Bioadhesive polymers play an important role in biomedical and drug delivery applications. The aim of this study is to develop a sustained- release tablet for local application of Cetylpyridinium Chloride (CPC). This delivery system would supply the drug at an effective level for a long period of time, and thereby overcome the problem of the short retention time of CPC and could be used for buccal delivery as a topical anti-infective agent. CPC bioadhesive tablets were directly prepared using 7 mm flat-faced punches on a hydraulic press. The materials for each tablet were weighted, introduced into the die and compacted at constant compression pressure. The dissolution tests were performed to the rotation paddle method and the bioadhesive strength of the tablets were measured. The results showed that as the concentration of polymer increased, the drug release rate was decreased. Also the type and ratio of polymers altered the release kinetic of Cetylpyridinium Chloride from investigated tablets. The bioadhesion strength increased with increasing the concentration of polymer and maximum bioadhesion strength was observed with HPMC K100M. The selected formulation of CPC bioadhesive tablet can be used as a suitable preparation for continuous release of CPC with appropriate bioadhesion strength.

Optimization of a Multi-Product Intra-Supply Chain System with Failure in Rework.

PubMed

Chiu, Singa Wang; Chen, Shin-Wei; Chang, Chih-Kai; Chiu, Yuan-Shyi Peter

2016-01-01

Globalization has created tremendous opportunities, but also made business environment highly competitive and turbulent. To gain competitive advantage, management of present-day transnational firms always seeks options to trim down various transaction and coordination costs, especially in the area of controllable intra-supply chain system. This study investigates a multi-product intra-supply chain system with failure in rework. To achieve maximum machine utilization, multiple products are fabricated in succession on a single machine. During the process, production of some defective items is inevitable. Reworking of nonconforming items is used to reduce the quality cost in production and achieving the goal of lower overall production cost. Because reworks are sometimes unsuccessful, failures in rework are also considered in this study. Finished goods for each product are transported to the sales offices when the entire production lot is quality assured after rework. A multi-delivery policy is used, wherein fixed quantity n installments of the finished lot are transported at fixed intervals during delivery time. The objective is to jointly determine the common production cycle time and the number of deliveries needed to minimize the long-term expected production-inventory-delivery costs for the problem. With the help of a mathematical model along with optimization technique, the optimal production-shipment policy is obtained. We have used a numerical example to demonstrate applicability of the result of our research.

Optimization of a Multi–Product Intra-Supply Chain System with Failure in Rework

PubMed Central

2016-01-01

Globalization has created tremendous opportunities, but also made business environment highly competitive and turbulent. To gain competitive advantage, management of present-day transnational firms always seeks options to trim down various transaction and coordination costs, especially in the area of controllable intra-supply chain system. This study investigates a multi–product intra-supply chain system with failure in rework. To achieve maximum machine utilization, multiple products are fabricated in succession on a single machine. During the process, production of some defective items is inevitable. Reworking of nonconforming items is used to reduce the quality cost in production and achieving the goal of lower overall production cost. Because reworks are sometimes unsuccessful, failures in rework are also considered in this study. Finished goods for each product are transported to the sales offices when the entire production lot is quality assured after rework. A multi-delivery policy is used, wherein fixed quantity n installments of the finished lot are transported at fixed intervals during delivery time. The objective is to jointly determine the common production cycle time and the number of deliveries needed to minimize the long–term expected production–inventory–delivery costs for the problem. With the help of a mathematical model along with optimization technique, the optimal production–shipment policy is obtained. We have used a numerical example to demonstrate applicability of the result of our research. PMID:27918588

Sonophoresis Using Ultrasound Contrast Agents: Dependence on Concentration.

PubMed

Park, Donghee; Song, Gillsoo; Jo, Yongjun; Won, Jongho; Son, Taeyoon; Cha, Ohrum; Kim, Jinho; Jung, Byungjo; Park, Hyunjin; Kim, Chul-Woo; Seo, Jongbum

2016-01-01

Sonophoresis can increase skin permeability to various drugs in transdermal drug delivery. Cavitation is recognized as the predominant mechanism of sonophoresis. Recently, a new logical approach to enhance the efficiency of transdermal drug delivery was tried. It is to utilize the engineered microbubble and its resonant frequency for increase of cavitation activity. Actively-induced cavitation with low-intensity ultrasound (less than ~1 MPa) causes disordering of the lipid bilayers and the formation of aqueous channels by stable cavitation which indicates a continuous oscillation of bubbles. Furthermore, the mutual interactions of microbubble determined by concentration of added bubble are also thought to be an important factor for activity of stable cavitation, even in different characteristics of drug. In the present study, we addressed the dependence of ultrasound contrast agent concentration using two types of drug on the efficiency of transdermal drug delivery. Two types of experiment were designed to quantitatively evaluate the efficiency of transdermal drug delivery according to ultrasound contrast agent concentration. First, an experiment of optical clearing using a tissue optical clearing agent was designed to assess the efficiency of sonophoresis with ultrasound contrast agents. Second, a Franz diffusion cell with ferulic acid was used to quantitatively determine the amount of drug delivered to the skin sample by sonophoresis with ultrasound contrast agents. The maximum enhancement ratio of sonophoresis with a concentration of 1:1,000 was approximately 3.1 times greater than that in the ultrasound group without ultrasound contrast agent and approximately 7.5 times greater than that in the control group. These results support our hypothesis that sonophoresis becomes more effective in transdermal drug delivery due to the presence of engineered bubbles, and that the efficiency of transdermal drug delivery using sonophoresis with microbubbles depends on the concentration of microbubbles in case stable cavitation is predominant.

Systemic Delivery of Atropine Sulfate by the MicroDose Dry-Powder Inhaler

PubMed Central

Venkataramanan, R.; Hoffman, R.M.; George, M.P.; Petrov, A.; Richards, T.; Zhang, S.; Choi, J.; Gao, Y.Y.; Oakum, C.D.; Cook, R.O.; Donahoe, M.

2013-01-01

Abstract Background Inhaled atropine is being developed as a systemic and pulmonary treatment for the extended recovery period after chemical weapons exposure. We performed a pharmacokinetics study comparing inhaled atropine delivery using the MicroDose Therapeutx Dry Powder Inhaler (DPIA) with intramuscular (IM) atropine delivery via auto-injector (AUTO). Methods The MicroDose DPIA utilizes a novel piezoelectric system to aerosolize drug and excipient from a foil dosing blister. Subjects inhaled a 1.95-mg atropine sulfate dose from the dry powder inhaler on one study day [5 doses×0.4 mg per dose (nominal) delivered over 12 min] and received a 2-mg IM injection via the AtroPen® auto-injector on another. Pharmacokinetics, pharmacodynamic response, and safety were studied for 12 hr. Results A total of 17 subjects were enrolled. All subjects completed IM dosing. One subject did not perform inhaled delivery due to a skin reaction from the IM dose. Pharmacokinetic results were as follows: area under the curve concentration, DPIA=20.1±5.8, AUTO=23.7±4.9 ng hr/mL (means±SD); maximum concentration reached, DPIA=7.7±3.5, AUTO=11.0±3.8 ng/mL; time to reach maximum concentration, DPIA=0.25±0.47, AUTO=0.19±0.23 hr. Pharmacodynamic results were as follows: maximum increase in heart rate, DPIA=18±12, AUTO=23±13 beats/min; average change in 1-sec forced expiratory volume at 30 min, DPIA=0.16±0.22 L, AUTO=0.11±0.29 L. The relative bioavailability for DPIA was 87% (based on output dose). Two subjects demonstrated allergic responses: one to the first dose (AUTO), which was mild and transient, and one to the second dose (DPIA), which was moderate in severity, required treatment with oral and intravenous (IV) diphenhydramine and IV steroids, and lasted more than 7 days. Conclusions Dry powder inhalation is a highly bioavailable route for attaining rapid and consistent systemic concentrations of atropine. PMID:22691110

Systemic delivery of atropine sulfate by the MicroDose Dry-Powder Inhaler.

PubMed

Corcoran, T E; Venkataramanan, R; Hoffman, R M; George, M P; Petrov, A; Richards, T; Zhang, S; Choi, J; Gao, Y Y; Oakum, C D; Cook, R O; Donahoe, M

2013-02-01

Inhaled atropine is being developed as a systemic and pulmonary treatment for the extended recovery period after chemical weapons exposure. We performed a pharmacokinetics study comparing inhaled atropine delivery using the MicroDose Therapeutx Dry Powder Inhaler (DPIA) with intramuscular (IM) atropine delivery via auto-injector (AUTO). The MicroDose DPIA utilizes a novel piezoelectric system to aerosolize drug and excipient from a foil dosing blister. Subjects inhaled a 1.95-mg atropine sulfate dose from the dry powder inhaler on one study day [5 doses × 0.4 mg per dose (nominal) delivered over 12 min] and received a 2-mg IM injection via the AtroPen® auto-injector on another. Pharmacokinetics, pharmacodynamic response, and safety were studied for 12 hr. A total of 17 subjects were enrolled. All subjects completed IM dosing. One subject did not perform inhaled delivery due to a skin reaction from the IM dose. Pharmacokinetic results were as follows: area under the curve concentration, DPIA=20.1±5.8, AUTO=23.7±4.9 ng hr/mL (means±SD); maximum concentration reached, DPIA=7.7±3.5, AUTO=11.0±3.8 ng/mL; time to reach maximum concentration, DPIA=0.25±0.47, AUTO=0.19±0.23 hr. Pharmacodynamic results were as follows: maximum increase in heart rate, DPIA=18±12, AUTO=23±13 beats/min; average change in 1-sec forced expiratory volume at 30 min, DPIA=0.16±0.22 L, AUTO=0.11±0.29 L. The relative bioavailability for DPIA was 87% (based on output dose). Two subjects demonstrated allergic responses: one to the first dose (AUTO), which was mild and transient, and one to the second dose (DPIA), which was moderate in severity, required treatment with oral and intravenous (IV) diphenhydramine and IV steroids, and lasted more than 7 days. Dry powder inhalation is a highly bioavailable route for attaining rapid and consistent systemic concentrations of atropine.

SU-E-T-545: A MLC-Equipped Robotic Radiosurgery-Radiotherapy Combined System in Treating Hepatic Lesions: Delivery Efficiency as Compared to a Standard Linac for Treating Hepatic Lesions

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

Jin, L; Price, R; Wang, L

Purpose: The CyberKnife (CK) M6 Series introduced a mulitleaf collimator (MLC) beam for extending its capability to the conventional radiotherapy. This work is to investigate delivery efficiency of this system as compared to a standard Varian linac when treating hepatic lesions. Methods: Nine previously treated patients were divided into three groups with three patients in each. Group one: fractionated radiotherapy; Group two: SBRT-like treatments and Group three: fractionated radiotherapy targeting two PTVs. The clinically used plans were generated with the Eclipse treatment planning system (TPS). We re-planned these cases using a Mulitplan (MP) TPS for the CK M6 and normalizedmore » to the same PTV dose coverage. CK factors (CF) (defined as modulation scaling factor in this work), number of nodes (NN), number of MLC segments (NS) and beam delivery time (BT) with an estimated image interval of 60 seconds, were used for evaluation of delivery efficiency. Results: Generated plans from the MP and Eclipse TPS demonstrated the similar quality in terms of PTV confomality index, minimum and maximum PTV doses, and doses received by critical structures. Group one: CF ranged from 8.1 to 8.7, NN from 30 to 40, NS from 120 to 155 and BT from 20 to 23 minutes; group two: CF from 4.7 to 8.5, NN from 15 to 19, NS from 82 to 141 and BT from 18 to 24 minutes; and group three: CF from 7.9 to 10, NN from 47 to 49, NS from 110 to 113 and BT from 20 to 22 minutes. Conclusions: Delivery time is longer for the CK M6 than for the Varian linac (7.8 to 13.7 minutes). Further investigation will be necessary to determine if a PTV reduction from the tracking feature will shorten the delivery time without decreasing plan quality.« less

Utilizing Maximum Power Point Trackers in Parallel to Maximize the Power Output of a Solar (Photovoltaic) Array

DTIC Science & Technology

2012-12-01

photovoltaic (PV) system to use a maximum power point tracker ( MPPT ) to increase... photovoltaic (PV) system to use a maximum power point tracker ( MPPT ) to increase the power output of the solar array. Currently, most military... MPPT ) is an optimizing circuit that is used in conjunction with photovoltaic (PV) arrays to achieve the maximum delivery of power from the array

Determination of prospective displacement-based gate threshold for respiratory-gated radiation delivery from retrospective phase-based gate threshold selected at 4D CT simulation

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

Vedam, S.; Archambault, L.; Starkschall, G.

2007-11-15

Four-dimensional (4D) computed tomography (CT) imaging has found increasing importance in the localization of tumor and surrounding normal structures throughout the respiratory cycle. Based on such tumor motion information, it is possible to identify the appropriate phase interval for respiratory gated treatment planning and delivery. Such a gating phase interval is determined retrospectively based on tumor motion from internal tumor displacement. However, respiratory-gated treatment is delivered prospectively based on motion determined predominantly from an external monitor. Therefore, the simulation gate threshold determined from the retrospective phase interval selected for gating at 4D CT simulation may not correspond to the deliverymore » gate threshold that is determined from the prospective external monitor displacement at treatment delivery. The purpose of the present work is to establish a relationship between the thresholds for respiratory gating determined at CT simulation and treatment delivery, respectively. One hundred fifty external respiratory motion traces, from 90 patients, with and without audio-visual biofeedback, are analyzed. Two respiratory phase intervals, 40%-60% and 30%-70%, are chosen for respiratory gating from the 4D CT-derived tumor motion trajectory. From residual tumor displacements within each such gating phase interval, a simulation gate threshold is defined based on (a) the average and (b) the maximum respiratory displacement within the phase interval. The duty cycle for prospective gated delivery is estimated from the proportion of external monitor displacement data points within both the selected phase interval and the simulation gate threshold. The delivery gate threshold is then determined iteratively to match the above determined duty cycle. The magnitude of the difference between such gate thresholds determined at simulation and treatment delivery is quantified in each case. Phantom motion tests yielded coincidence of simulation and delivery gate thresholds to within 0.3%. For patient data analysis, differences between simulation and delivery gate thresholds are reported as a fraction of the total respiratory motion range. For the smaller phase interval, the differences between simulation and delivery gate thresholds are 8{+-}11% and 14{+-}21% with and without audio-visual biofeedback, respectively, when the simulation gate threshold is determined based on the mean respiratory displacement within the 40%-60% gating phase interval. For the longer phase interval, corresponding differences are 4{+-}7% and 8{+-}15% with and without audio-visual biofeedback, respectively. Alternatively, when the simulation gate threshold is determined based on the maximum average respiratory displacement within the gating phase interval, greater differences between simulation and delivery gate thresholds are observed. A relationship between retrospective simulation gate threshold and prospective delivery gate threshold for respiratory gating is established and validated for regular and nonregular respiratory motion. Using this relationship, the delivery gate threshold can be reliably estimated at the time of 4D CT simulation, thereby improving the accuracy and efficiency of respiratory-gated radiation delivery.« less

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-beam prostate motion range. Excellent delivery accuracy was confirmed with very small leaf motion deviation.« less

Nonclinical Development of ENV905 (Difluprednate) Ophthalmic Implant for the Treatment of Inflammation and Pain Associated with Ocular Surgery.

PubMed

Verhoeven, Rozemarijn S; Garcia, Andres; Robeson, RiLee; Gilger, Brian C; Culp, David; Struble, Craig; Hamm, Lee; Navratil, Tomas; Yerxa, Benjamin

Topical corticosteroids are widely used in the treatment of inflammation and pain after ocular surgery, but they possess several shortcomings, including frequent dosing and low patient adherence. We evaluated the efficacy and pharmacokinetics of ENV905 (difluprednate or DFBA) Ophthalmic Implant, a single-dose drug delivery system, compared with 0.05% Durezol. PRINT ® technology was used to fabricate ENV905 implants for either intracameral (IC) or subconjunctival (SCJ) delivery of extended-release DFBA. A postoperative inflammation model and ocular pharmacokinetics studies of ENV905 or Durezol were conducted in albino rabbits for a maximum of 12 weeks. Suppression of ocular inflammation was marked for both IC and SJC ENV905 compared with placebo, and it was superior or equivalent to that observed with QID Durezol. Concentrations of desacetyl difluprednate (DFB, active metabolite) peaked on day 1 and tapered over time for ENV905, with IC ENV905 delivering DFB to the target tissue at the time of greatest inflammation, whereas SJC produced a longer duration of exposure. Durezol eyes demonstrated consistent exposure over time with maximal exposure in the cornea. Although the pharmacokinetic profile differed for the two routes, efficacy was similar. ENV905 was well tolerated and demonstrated a robust reduction in ocular inflammation with targeted drug delivery. The results from these studies show that ENV905 provides a sustained therapeutic effect after a single dose. By resolving low patient compliance and eliminating the peaks and troughs in drug concentration, sustained drug delivery via ENV905 may further improve the overall control of postoperative inflammation and pain.

Parturition in horses is dominated by parasympathetic activity of the autonomous nervous system.

PubMed

Nagel, Christina; Erber, Regina; Ille, Natascha; von Lewinski, Mareike; Aurich, Jörg; Möstl, Erich; Aurich, Christine

2014-07-01

External and internal stressors prolong parturition in different species. At parturition, sympathoadrenal activation should be avoided because an increased sympathetic tone may cause uterine atonia via β2-receptors. We hypothesized that at physiological parturition, horses are under parasympathetic dominance, and stress-response mechanisms are not activated during delivery of the foal. To evaluate stress responses, heart rate, heart rate variability, catecholamines, and cortisol were analyzed in mares (n = 17) throughout foaling. Heart rate decreased from 2 hours before (51 ± 1 beats/minute) to 2 hours after delivery (41 ± 2 beats/minute; P < 0.05). Heart rate variability variables, standard deviation of the beat-to-beat interval, and root mean square of successive beat-to-beat differences, changed over time (P < 0.05) with the highest values within 15 minutes after delivery. The number of mares with atrioventricular blocks and the number of atrioventricular blocks per mare increased over time (P < 0.01) and were significantly elevated from 15 minutes before to 45 minutes after birth of the foal. Salivary cortisol concentrations increased to a maximum at 30 minutes after delivery (25.0 ± 3.4 ng/mL; P < 0.01). Plasma epinephrine and norepinephrine concentrations showed significant fluctuations from rupture of the allantochorion to expulsion of the fetal membranes (P < 0.01) but were not markedly elevated at any time. In conclusion, mares give birth under high parasympathetic tone. Cortisol release during and after foaling is most likely part of the endocrine pathways regulating parturition and not a labor-associated stress response. Copyright © 2014 Elsevier Inc. All rights reserved.

Novel non-ionic surfactant proniosomes for transdermal delivery of lacidipine: optimization using 2(3) factorial design and in vivo evaluation in rabbits.

PubMed

Soliman, Sara M; Abdelmalak, Nevine S; El-Gazayerly, Omaima N; Abdelaziz, Nabaweya

2016-06-01

Proniosomes offer a versatile vesicle drug delivery concept with potential for delivery of drugs via transdermal route. To develop proniosomal gel using cremophor RH 40 as non-ionic surfactant containing the antihypertensive drug lacidipine for transdermal delivery so as to avoid its extensive first pass metabolism and to improve its permeation through the skin. Proniosomes containing 1% lacidipine were prepared by the coacervation phase separation method, characterized, and optimized using a 2(3) full factorial design to define the optimum conditions to produce proniosomes with high entrapment efficiency, minimal vesicle size, and high-percentage release efficiency. The amount of cholesterol (X1), the amount of soya lecithin (X2), and the amount of cremophor RH 40 (X3) were selected as three independent variables. The system F4 was found to fulfill the maximum requisite of an optimum system because it had minimum vesicle size, maximum EE, maximum release efficiency, and maximum desirability. The optimized system (F4) was then converted to proniosomal gel using carbopol 940 (1% w/w). In vitro permeation through excised rabbit skin study revealed higher flux (6.48 ± 0.45) for lacidipine from the optimized proniosomal gel when compared with the corresponding emulgel (3.04 ± 0.13) mg/cm(2)/h. The optimized formulation was evaluated for its bioavailability compared with commercial product. Statistical analysis revealed significant increase in AUC (0 - α) 464.17 ± 113.15 ng h/ml compared with 209.02 ± 47.35 ng h/ml for commercial tablet. Skin irritancy and histopathological investigation of rat skin revealed its safety. Cremophor RH 40 proniosomal gel could be considered as very promising nanocarriers for transdermal delivery of lacidipine.

Closed-loop control of targeted ultrasound drug delivery across the blood–brain/tumor barriers in a rat glioma model

PubMed Central

Sun, Tao; Zhang, Yongzhi; Power, Chanikarn; Alexander, Phillip M.; Sutton, Jonathan T.; Aryal, Muna; Vykhodtseva, Natalia; Miller, Eric L.; McDannold, Nathan J.

2017-01-01

Cavitation-facilitated microbubble-mediated focused ultrasound therapy is a promising method of drug delivery across the blood–brain barrier (BBB) for treating many neurological disorders. Unlike ultrasound thermal therapies, during which magnetic resonance thermometry can serve as a reliable treatment control modality, real-time control of modulated BBB disruption with undetectable vascular damage remains a challenge. Here a closed-loop cavitation controlling paradigm that sustains stable cavitation while suppressing inertial cavitation behavior was designed and validated using a dual-transducer system operating at the clinically relevant ultrasound frequency of 274.3 kHz. Tests in the normal brain and in the F98 glioma model in vivo demonstrated that this controller enables reliable and damage-free delivery of a predetermined amount of the chemotherapeutic drug (liposomal doxorubicin) into the brain. The maximum concentration level of delivered doxorubicin exceeded levels previously shown (using uncontrolled sonication) to induce tumor regression and improve survival in rat glioma. These results confirmed the ability of the controller to modulate the drug delivery dosage within a therapeutically effective range, while improving safety control. It can be readily implemented clinically and potentially applied to other cavitation-enhanced ultrasound therapies. PMID:29133392

Sci—Sat AM: Stereo — 02: Implementation of a VMAT class solution for kidney SBRT

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

Sonier, M; Lalani, N; Korol, R

An emerging treatment option for inoperable primary renal cell carcinoma and oligometastatic adrenal lesions is stereotactic body radiation therapy (SBRT). At our center, kidney SBRT treatments were originally planned with IMRT. The goal was to plan future patients using VMAT to improve treatment delivery efficiency. The purpose of this work was twofold: 1) to develop a VMAT class solution for the treatment of kidney SBRT; and, 2) to assess VMAT plan quality when compared to IMRT plans. Five patients treated with IMRT for kidney SBRT were reviewed and replanned in Pinnacle using a single VMAT arc with a 15° collimatormore » rotation, constrained leaf motion and 4° gantry spacing. In comparison, IMRT plans utilized 7–9 6MV beams, with various collimator rotations and up to 2 non-coplanar beams for maximum organ-at-risk (OAR) sparing. Comparisons were made concerning target volume conformity, homogeneity, dose to OARs, treatment time and monitor units (MUs). There was no difference in MUs; however, VMAT reduced the treatment time from 13.0±2.6min, for IMRT, to 4.0±0.9min. The collection of target and OAR constraints and SmartArc parameters, produced a class solution that generated VMAT plans with increased target homogeneity and improved 95% conformity index calculated at < 1.2. In general, the VMAT plans displayed a reduced maximum point dose to nearby OARs with increased intermediate dose to distant OARs. Overall, the introduction of a VMAT class solution for kidney SBRT improves efficiency by reducing treatment planning and delivery time.« less

Effect of occlusal splint therapy on maximum bite force in individuals with moderate to severe attrition of teeth.

PubMed

Jain, Veena; Mathur, Vijay Prakash; Abhishek, Kumar; Kothari, Mohit

2012-10-01

The purpose of the pilot study was to determine the effect of restoring lost occlusal vertical dimension (OVD) due to attrition on maximum bite force in humans. A total of 124 subjects in age range of 25-40 years, with moderate to severe attrition, having full complement of teeth were screened according to inclusion and exclusion criteria. After consent, occlusal vertical dimension was assessed by employing mechanical and physiological methods in the experimental group and a maxillary canine guided hard splint was fabricated for each subjects fulfilling inclusion criteria and with positive consent (78). Bite force in experimental group was measured before, immediately after delivery of splint and subsequently at an interval of four, eight, and twelve weeks. Due loss during follow up, only 50 subjects could be available for bite force recording till 12 weeks. Bite force of age, gender, height and weight matched controls with no signs of attrition was also measured for comparison. Bite force of the experimental group was found to be significantly less than the matched controls (P=0.000) initially. After delivery of splint, bite force values increased progressively till twelve weeks. However comparison of bite force values of experimental group with control group showed no significant difference at end of eight (P=0.008) and twelve weeks (P=0.162). It was concluded that maximum bite force increases with restoration of lost vertical using splint therapy. A time period of 8-12 weeks is required to restore the maximum bite force value approximately similar to matched controls. Copyright © 2012 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

Selecting the Right Construction Delivery Method for a Specific Project.

ERIC Educational Resources Information Center

Klinger, Jeff; Booth, Scott

2002-01-01

Discusses the costs and benefits of various construction delivery methods for higher education facility projects, including the traditional lump sum general contracting approach (also known as design/bid/build); design-build; and, in the case of private institutions, guaranteed maximum pricing offered by those firms willing to perform construction…

Investigation of pulsed IMRT and VMAT for re-irradiation treatments: dosimetric and delivery feasibilities

NASA Astrophysics Data System (ADS)

Lin, Mu-Han; Price, Robert A., Jr.; Li, Jinsheng; Kang, Shengwei; Li, Jie; Ma, C.-M.

2013-11-01

Many tumor cells demonstrate hyperradiosensitivity at doses below ˜50 cGy. Together with the increased normal tissue repair under low dose rate, the pulsed low dose rate radiotherapy (PLDR), which separates a daily fractional dose of 200 cGy into 10 pulses with 3 min interval between pulses (˜20 cGy/pulse and effective dose rate 6.7 cGy min-1), potentially reduces late normal tissue toxicity while still providing significant tumor control for re-irradiation treatments. This work investigates the dosimetric and technical feasibilities of intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT)-based PLDR treatments using Varian Linacs. Twenty one cases (12 real re-irradiation cases) including treatment sites of pancreas, prostate, pelvis, lung, head-and-neck, and breast were recruited for this study. The lowest machine operation dose rate (100 MU min-1) was employed in the plan delivery. Ten-field step-and-shoot IMRT and dual-arc VMAT plans were generated using the Eclipse TPS with routine planning strategies. The dual-arc plans were delivered five times to achieve a 200 cGy daily dose (˜20 cGy arc-1). The resulting plan quality was evaluated according to the heterogeneity and conformity indexes (HI and CI) of the planning target volume (PTV). The dosimetric feasibility of retaining the hyperradiosensitivity for PLDR was assessed based on the minimum and maximum dose in the target volume from each pulse. The delivery accuracy of VMAT and IMRT at the 100 MU min-1 machine operation dose rate was verified using a 2D diode array and ion chamber measurements. The delivery reproducibility was further investigated by analyzing the Dynalog files of repeated deliveries. A comparable plan quality was achieved by the IMRT (CI 1.10-1.38 HI 1.04-1.10) and the VMAT (CI 1.08-1.26 HI 1.05-1.10) techniques. The minimum/maximum PTV dose per pulse is 7.9 ± 5.1 cGy/33.7 ± 6.9 cGy for the IMRT and 12.3 ± 4.1 cGy/29.2 ± 4.7 cGy for the VMAT. Six out of the 186 IMRT pulses (fields) were found to exceed 50 cGy maximum PTV dose per pulse while the maximum PTV dose per pulse was within 40 cGy for all the VMAT pulses (arcs). However, for VMAT plans, the dosimetric quality of the entire treatment plan was less superior for the breast cases and large irregular targets. The gamma passing rates for both techniques at the 100 MU min-1 dose rate were at least 94.1% (3%/3 mm) and the point dose measurements agreed with the planned values to within 2.2%. The average root mean square error of the leaf position was 0.93 ± 0.83 mm for IMRT and 0.53 ± 0.48 mm for VMAT based on the Dynalog file analysis. The RMS error of the leaf position was nearly identical for the repeated deliveries of the same plans. In general, both techniques are feasible for PLDR treatments. VMAT was more advantageous for PLDR with more uniform target dose per pulse, especially for centrally located tumors. However, for large, irregular and/or peripheral tumors, IMRT could produce more favorable PLDR plans. By taking the biological benefit of PLDR delivery and the dosimetric benefit of IMRT and VMAT, the proposed methods have a great potential for those previously-irradiated recurrent patients.

TU-AB-303-03: CBCT-Based On-Site Simulation, Planning, and Delivery (OSPD) for Whole Brain Radiotherapy

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

Le, A; Choe, K; Jiang, S

2015-06-15

Purpose: To demonstrate the feasibility of a CBCT-based on-site simulation, planning, and delivery (OSPD) for whole brain radiotherapy, in which all steps from imaging, planning to treatment delivery are performed at the treatment unit in one appointment time slot. This work serves as the proof of concept for future OSPD single fraction radiation therapy. Methods: An integrated on-site imaging, planning and delivery workflow was developed and tested for whole brain radiotherapy. An automated two-opposed-oblique-beam plan is created by utilizing the treatment planning system scripting and simple field-in-field IMRT. The IMRT plan is designed with maximum 8 control points to covermore » the target volume consisting of the brain to C1/C2 of the spinal cord, with dose homogeneity criteria from −5% to +7% of the prescription dose. Due to inaccuracy of reconstructed Hounsfield unit numbers in CBCT images, the dose distribution is calculated with non-heterogeneity correction introducing only clinically insignificant dose discrepancy. A coherent and synchronized workflow was designed for a team of attending physician, physicist, therapists, and dosimetrist to work closely with the ability to quickly modify, approve, and implement the treatment. Results: Thirty-one patients have been treated with this OSPD treatment, without compromising the plan quality compared to our regular clinically used parallel apposed 2D plans. The average time for these procedures are 48.02 ±11.55 minutes from the time patient entered the treatment room until s/he exited, and 35.09 ±10.35 minutes from starting CBCT until last beam delivered. This time duration is comparable to the net time when individual tasks are summed up during our regular CT- based whole brain planning and delivery. Conclusions: The OSPD whole brain treatment has been tested to be clinically feasible. The next step is to further improve the efficiency and to streamline the workflow. Other disease sites will be also tested with this new technology.« less

Defining the health care product to ensure quality and manage costs.

PubMed

Burns, J

1994-02-01

The frenzy of health care reform activity now led by the Clinton Administration's American Health Security Act of 1993 might end in the worst of all possible outcomes: a new government entitlement program financed by business and a global budget. Unbridled entitlement could drive utilization of benefits to the maximum and, with a budget cap, guarantee rationing. So far, the administration has talked about expanding access and controlling costs--not about the health care product. Given the threat that change poses for vested interests, time will undoubtedly lapse before final implementation of a new system. Unless physicians involved in health management seize the opportunity during this window of opportunity to help shape the future of health care delivery, the likelihood of preserving the U.S. health care delivery system as we know it will be dim indeed.

Assessing Modeled CO2 Retention and Rebreathing of a Facemask Designed for Efficient Delivery of Aerosols to Infants

PubMed Central

Mundt, Christian; Sventitskiy, Alexander; Cehelsky, Jeffrey E.; Patters, Andrea B.; Tservistas, Markus; Hahn, Michael C.; Juhl, Gerd; DeVincenzo, John P.

2012-01-01

Background. New aerosol drugs for infants may require more efficient delivery systems, including face masks. Maximizing delivery efficiency requires tight-fitting masks with minimal internal mask volumes, which could cause carbon dioxide (CO2) retention. An RNA-interference-based antiviral for treatment of respiratory syncytial virus in populations that may include young children is designed for aerosol administration. CO2 accumulation within inhalation face masks has not been evaluated. Methods. We simulated airflow and CO2 concentrations accumulating over time within a new facemask designed for infants and young children (PARI SMARTMASK® Baby). A one-dimensional model was first examined, followed by 3-dimensional unsteady computational fluid dynamics analyses. Normal infant breathing patterns and respiratory distress were simulated. Results. The maximum average modeled CO2 concentration within the mask reached steady state (3.2% and 3% for normal and distressed breathing patterns resp.) after approximately the 5th respiratory cycle. After steady state, the mean CO2 concentration inspired into the nostril was 2.24% and 2.26% for normal and distressed breathing patterns, respectively. Conclusion. The mask is predicted to cause minimal CO2 retention and rebreathing. Infants with normal and distressed breathing should tolerate the mask intermittently delivering aerosols over brief time frames. PMID:22792479

Interaction between shock wave and single inertial bubbles near an elastic boundary.

PubMed

Sankin, G N; Zhong, P

2006-10-01

The interaction of laser-generated single inertial bubbles (collapse time = 121 mus) near a silicon rubber membrane with a shock wave (55 MPa in peak pressure and 1.7 mus in compressive pulse duration) is investigated. The interaction leads to directional, forced asymmetric collapse of the bubble with microjet formation toward the surface. Maximum jet penetration into the membrane is produced during the bubble collapse phase with optimal shock wave arrival time and stand-off distance. Such interaction may provide a unique acoustic means for in vivo microinjection, applicable to targeted delivery of macromolecules and gene vectors to biological tissues.

Thirty years of the World Health Organization's target caesarean section rate: time to move on.

PubMed

Robson, Stephen J; de Costa, Caroline M

2017-03-06

It has been 30 years since the World Health Organization first recommended a "maximum" caesarean section (CS) rate of 15%. There are demographic differences across the 194 WHO member countries; recent analyses suggest the optimal global CS rate is almost 20%. Attempts to reduce CS rates in developed countries have not worked. The strongest predictor of caesarean delivery for the first birth of "low risk" women appears to be maternal age; a factor that continues to increase. Most women whose first baby is born by caesarean delivery will have all subsequent children by caesarean delivery. Outcomes that informed the WHO recommendation primarily relate to maternal and perinatal mortality, which are easy to measure. Longer term outcomes, such as pelvic organ prolapse and urinary incontinence, are closely related to mode of birth, and up to 20% of women will undergo surgery for these conditions. Pelvic floor surgery is typically undertaken for older women who are less fit for surgery. Serious complications such as placenta accreta occur with repeat caesarean deliveries, but the odds only reach statistical significance at the third or subsequent caesarean delivery. However, in Australia, parity is falling, and only 20% of women will have more than two births. We should aim to provide CS to women in need and to continue including women in the conversation about the benefits and disadvantages, both short and long term, of birth by caesarean delivery.

Efficient bounding schemes for the two-center hybrid flow shop scheduling problem with removal times.

PubMed

Hidri, Lotfi; Gharbi, Anis; Louly, Mohamed Aly

2014-01-01

We focus on the two-center hybrid flow shop scheduling problem with identical parallel machines and removal times. The job removal time is the required duration to remove it from a machine after its processing. The objective is to minimize the maximum completion time (makespan). A heuristic and a lower bound are proposed for this NP-Hard problem. These procedures are based on the optimal solution of the parallel machine scheduling problem with release dates and delivery times. The heuristic is composed of two phases. The first one is a constructive phase in which an initial feasible solution is provided, while the second phase is an improvement one. Intensive computational experiments have been conducted to confirm the good performance of the proposed procedures.

Efficient Bounding Schemes for the Two-Center Hybrid Flow Shop Scheduling Problem with Removal Times

PubMed Central

2014-01-01

We focus on the two-center hybrid flow shop scheduling problem with identical parallel machines and removal times. The job removal time is the required duration to remove it from a machine after its processing. The objective is to minimize the maximum completion time (makespan). A heuristic and a lower bound are proposed for this NP-Hard problem. These procedures are based on the optimal solution of the parallel machine scheduling problem with release dates and delivery times. The heuristic is composed of two phases. The first one is a constructive phase in which an initial feasible solution is provided, while the second phase is an improvement one. Intensive computational experiments have been conducted to confirm the good performance of the proposed procedures. PMID:25610911

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

49 CFR 180.416 - Discharge system inspection and maintenance program for cargo tanks transporting liquefied...

Code of Federal Regulations, 2011 CFR

2011-10-01

... unique identification number and maximum working pressure. (c) Post-delivery hose check. After each... unloading. (d) Monthly inspections and tests. (1) The operator must visually inspect each delivery hose... actuate all emergency discharge control devices designed to close the internal self-closing stop valve to...

49 CFR 180.416 - Discharge system inspection and maintenance program for cargo tanks transporting liquefied...

Code of Federal Regulations, 2014 CFR

2014-10-01

... unique identification number and maximum working pressure. (c) Post-delivery hose check. After each... unloading. (d) Monthly inspections and tests. (1) The operator must visually inspect each delivery hose... actuate all emergency discharge control devices designed to close the internal self-closing stop valve to...

49 CFR 180.416 - Discharge system inspection and maintenance program for cargo tanks transporting liquefied...

Code of Federal Regulations, 2013 CFR

2013-10-01

... unique identification number and maximum working pressure. (c) Post-delivery hose check. After each... unloading. (d) Monthly inspections and tests. (1) The operator must visually inspect each delivery hose... actuate all emergency discharge control devices designed to close the internal self-closing stop valve to...

49 CFR 180.416 - Discharge system inspection and maintenance program for cargo tanks transporting liquefied...

Code of Federal Regulations, 2012 CFR

2012-10-01

... unique identification number and maximum working pressure. (c) Post-delivery hose check. After each... unloading. (d) Monthly inspections and tests. (1) The operator must visually inspect each delivery hose... actuate all emergency discharge control devices designed to close the internal self-closing stop valve to...

Effect of ibuprofen vs acetaminophen on postpartum hypertension in preeclampsia with severe features: a double-masked, randomized controlled trial.

PubMed

Blue, Nathan R; Murray-Krezan, Cristina; Drake-Lavelle, Shana; Weinberg, Daniel; Holbrook, Bradley D; Katukuri, Vivek R; Leeman, Lawrence; Mozurkewich, Ellen L

2018-06-01

Nonsteroidal antiinflammatory drug use has been shown to increase blood pressure in nonpregnant adults. Because of this, the American College of Obstetricians and Gynecologists suggests avoiding their use in women with postpartum hypertension; however, evidence to support this recommendation is lacking. Our goal was to test the hypothesis that nonsteroidal antiinflammatory drugs, such as ibuprofen, adversely affect postpartum blood pressure control in women with preeclampsia with severe features. At delivery, we randomized women with preeclampsia with severe features to receive around-the-clock oral dosing with either 600 mg of ibuprofen or 650 mg of acetaminophen every 6 hours. Dosing began within 6 hours after delivery and continued until discharge, with opioid analgesics available as needed for breakthrough pain. Study drugs were encapsulated in identical capsules such that patients, nurses, and physicians were masked to study allocation. Exclusion criteria were serum aspartate aminotransferase or alanine aminotransferase >200 mg/dL, serum creatinine >1.0 mg/dL, infectious hepatitis, gastroesophageal reflux disease, age <18 years, or current incarceration. Our primary outcome was the duration of severe-range hypertension, defined as the time (in hours) from delivery to the last blood pressure ≥160/110 mm Hg. Secondary outcomes were time from delivery to last blood pressure ≥150/100 mm Hg, mean arterial pressure, need for antihypertensive medication at discharge, prolongation of hospital stay for blood pressure control, postpartum use of short-acting antihypertensives for acute blood pressure control, and opioid use for breakthrough pain. We analyzed all outcome data according to intention-to-treat principles. We assessed 154 women for eligibility, of whom 100 met entry criteria, agreed to participate, and were randomized to receive postpartum ibuprofen or acetaminophen for first-line pain control. Seven patients crossed over or did not receive their allocated study drug, and 93 completed the study protocol in their assigned groups. We found no differences in baseline characteristics between groups, including mode of delivery, body mass index, parity, race, chronic hypertension, and maximum blood pressure prior to delivery. We did not find a difference in the duration of severe-range hypertension in the ibuprofen vs acetaminophen groups (35.3 vs 38.0 hours, P = .30). There were no differences between groups in the secondary outcome measures of time from delivery to last blood pressure ≥150/100 mm Hg, postpartum mean arterial pressure, maximum postpartum systolic or diastolic blood pressures, any postpartum blood pressure ≥160/110 mm Hg, short-acting antihypertensive use for acute blood pressure control, length of postpartum stay, need to extend postpartum stay for blood pressure control, antihypertensive use at discharge, or opioid use for inadequate pain control. In a subgroup analysis of patients who experienced severe-range hypertension, the mean time to blood pressure control in the acetaminophen group was 68.4 hours and ibuprofen group was 56.7 hours (P = .26). At 6 weeks postpartum, there were no differences between groups in the rates of obstetric triage visits, hospital readmissions, continued opioid use, or continued antihypertensive use. The first-line use of ibuprofen rather than acetaminophen for postpartum pain did not lengthen the duration of severe-range hypertension in women with preeclampsia with severe features. Copyright © 2018 Elsevier Inc. All rights reserved.

Cavitation-enhanced extravasation for drug delivery.

PubMed

Arvanitis, Costas D; Bazan-Peregrino, Miriam; Rifai, Bassel; Seymour, Leonard W; Coussios, Constantin C

2011-11-01

A flow-through tissue-mimicking phantom composed of a biocompatible hydro-gel with embedded tumour cells was used to assess and optimize the role of ultrasound-induced cavitation on the extravasation of a macromolecular compound from a channel mimicking vessel in the gel, namely a non-replicating luciferase-expressing adenovirus (Ad-Luc). Using a 500 KHz therapeutic ultrasound transducer confocally aligned with a focussed passive cavitation detector, different exposure conditions and burst mode timings were selected by performing time and frequency domain analysis of passively recorded acoustic emissions, in the absence and in the presence of ultrasound contrast agents acting as cavitation nuclei. In the presence of Sonovue, maximum ultraharmonic emissions were detected for peak rarefactional pressures of 360 kPa, and maximum broadband emissions occurred at 1250 kPa. The energy of the recorded acoustic emissions was used to optimise the pulse repetition frequency and duty cycle in order to maximize either ultraharmonic or broadband emissions while keeping the acoustic energy delivered to the focus constant. Cell viability measurements indicated that none of the insonation conditions investigated induces cell death in the absence of a therapeutic agent (i.e. virus). Phase contrast images of the tissue-mimicking phantom showed that short range vessel disruption can occur when ultra-harmonic emissions (nf0/2) are maximised whereas formation of a micro-channel perpendicular to the flow can be obtained in the presence of broadband acoustic emissions. Following Ad-Luc delivery, luciferase expression measurements showed that a 60-fold increase in its bioavailability can be achieved when broadband noise emissions are present during insonation, even for modest contrast agent concentrations. The findings of the present study suggest that drug delivery systems based on acoustic cavitation may help enhance the extravasation of anticancer agents, thus increasing their penetration distance to hypoxic regions and poorly vascularised tumour regions. Copyright © 2011 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Efficiency gains for spinal radiosurgery using multicriteria optimization intensity modulated radiation therapy guided volumetric modulated arc therapy planning.

PubMed

Chen, Huixiao; Winey, Brian A; Daartz, Juliane; Oh, Kevin S; Shin, John H; Gierga, David P

2015-01-01

To evaluate plan quality and delivery efficiency gains of volumetric modulated arc therapy (VMAT) versus a multicriteria optimization-based intensity modulated radiation therapy (MCO-IMRT) for stereotactic radiosurgery of spinal metastases. MCO-IMRT plans (RayStation V2.5; RaySearch Laboratories, Stockholm, Sweden) of 10 spinal radiosurgery cases using 7-9 beams were developed for clinical delivery, and patients were replanned using VMAT with partial arcs. The prescribed dose was 18 Gy, and target coverage was maximized such that the maximum dose to the planning organ-at-risk volume (PRV) of the spinal cord was 10 or 12 Gy. Dose-volume histogram (DVH) constraints from the clinically acceptable MCO-IMRT plans were utilized for VMAT optimization. Plan quality and delivery efficiency with and without collimator rotation for MCO-IMRT and VMAT were compared and analyzed based upon DVH, planning target volume coverage, homogeneity index, conformity number, cord PRV sparing, total monitor units (MU), and delivery time. The VMAT plans were capable of matching most DVH constraints from the MCO-IMRT plans. The ranges of MU were 4808-7193 for MCO-IMRT without collimator rotation, 3509-5907 for MCO-IMRT with collimator rotation, 4444-7309 for VMAT without collimator rotation, and 3277-5643 for VMAT with collimator of 90 degrees. The MU for the VMAT plans were similar to their corresponding MCO-IMRT plans, depending upon the complexity of the target and PRV geometries, but had a larger range. The delivery times of the MCO-IMRT and VMAT plans, both with collimator rotation, were 18.3 ± 2.5 minutes and 14.2 ± 2.0 minutes, respectively (P < .05). The MCO-IMRT and VMAT can create clinically acceptable plans for spinal radiosurgery. The MU for MCO-IMRT and VMAT can be reduced significantly by utilizing a collimator rotation following the orientation of the spinal cord. Plan quality for VMAT is similar to MCO-IMRT, with similar MU for both modalities. Delivery times can be reduced by nominally 25% with VMAT. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

77 FR 62446 - Every Door Direct Mail-Retail

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-15

..., the maximum number of EDDM-Retail pieces per day is 5000 per 5-digit ZIP Code. 1.3 Delivery Statistics...) under 145, using delivery statistics obtained from the EDDM web tool at the Web site eddm.usps.com/eddm... title and introductory text of 2.2.2 as follows:] 2.2.2 Dimensions for Standard Mail and EDDM-Retail...

A low power, microvalve regulated architecture for drug delivery systems.

PubMed

Evans, Allan Thomas; Park, Jong M; Chiravuri, Srinivas; Gianchandani, Yogesh B

2010-02-01

This paper describes an actively-controlled architecture for drug delivery systems that offers high performance and volume efficiency through the use of micromachined components. The system uses a controlled valve to regulate dosing by throttling flow from a mechanically pressurized reservoir, thereby eliminating the need for a pump. To this end, the valve is fabricated from a glass wafer and silicon-on-insulator wafer for sensor integration. The valve draws a maximum power of 1.68 μW| (averaged over time); with the existing packaging scheme, it has a volume of 2.475 cm3. The reservoirs are assembled by compressing polyethylene terephthalate polymer balloons with metal springs. The metal springs are fabricated from Elgiloy® using photochemical etching. The springs pressurize the contents of 37 mLchambers up to 15 kPa. The system is integrated with batteries and a control circuit board within a 113 cm3 metal casing. This system has been evaluated in different control modes to mimic clinical applications. Bolus deliveries of1.5 mL have been regulated as well as continuous flows of 0.15 mL/day with accuracies of 3.22%. The results suggest that this device can be used in an implant to regulate intrathecal drug delivery

Noncoplanar VMAT for nasopharyngeal tumors: Plan quality versus treatment time.

PubMed

Wild, Esther; Bangert, Mark; Nill, Simeon; Oelfke, Uwe

2015-05-01

The authors investigated the potential of optimized noncoplanar irradiation trajectories for volumetric modulated arc therapy (VMAT) treatments of nasopharyngeal patients and studied the trade-off between treatment plan quality and delivery time in radiation therapy. For three nasopharyngeal patients, the authors generated treatment plans for nine different delivery scenarios using dedicated optimization methods. They compared these scenarios according to dose characteristics, number of beam directions, and estimated delivery times. In particular, the authors generated the following treatment plans: (1) a 4π plan, which is a not sequenced, fluence optimized plan that uses beam directions from approximately 1400 noncoplanar directions and marks a theoretical upper limit of the treatment plan quality, (2) a coplanar 2π plan with 72 coplanar beam directions as pendant to the noncoplanar 4π plan, (3) a coplanar VMAT plan, (4) a coplanar step and shoot (SnS) plan, (5) a beam angle optimized (BAO) coplanar SnS IMRT plan, (6) a noncoplanar BAO SnS plan, (7) a VMAT plan with rotated treatment couch, (8) a noncoplanar VMAT plan with an optimized great circle around the patient, and (9) a noncoplanar BAO VMAT plan with an arbitrary trajectory around the patient. VMAT using optimized noncoplanar irradiation trajectories reduced the mean and maximum doses in organs at risk compared to coplanar VMAT plans by 19% on average while the target coverage remains constant. A coplanar BAO SnS plan was superior to coplanar SnS or VMAT; however, noncoplanar plans like a noncoplanar BAO SnS plan or noncoplanar VMAT yielded a better plan quality than the best coplanar 2π plan. The treatment plan quality of VMAT plans depended on the length of the trajectory. The delivery times of noncoplanar VMAT plans were estimated to be 6.5 min in average; 1.6 min longer than a coplanar plan but on average 2.8 min faster than a noncoplanar SnS plan with comparable treatment plan quality. The authors' study reconfirms the dosimetric benefits of noncoplanar irradiation of nasopharyngeal tumors. Both SnS using optimized noncoplanar beam ensembles and VMAT using an optimized, arbitrary, noncoplanar trajectory enabled dose reductions in organs at risk compared to coplanar SnS and VMAT. Using great circles or simple couch rotations to implement noncoplanar VMAT, however, was not sufficient to yield meaningful improvements in treatment plan quality. The authors estimate that noncoplanar VMAT using arbitrary optimized irradiation trajectories comes at an increased delivery time compared to coplanar VMAT yet at a decreased delivery time compared to noncoplanar SnS IMRT.

Contactless and non-invasive delivery of micro-particles lying on a non-customized rigid surface by using acoustic radiation force.

PubMed

Meng, Jianxin; Mei, Deqing; Jia, Kun; Fan, Zongwei; Yang, Keji

2014-07-01

In the existing acoustic micro-particle delivery methods, the micro-particles always lie and slide on the surface of platform in the whole delivery process. To avoid the damage and contamination of micro-particles caused by the sliding motion, this paper deals with a novel approach to trap micro-particles from non-customized rigid surfaces and freely manipulate them. The delivery process contains three procedures: detaching, transporting, and landing. Hence, the micro-particles no longer lie on the surface, but are levitated in the fluid, during the long range transporting procedure. It is very meaningful especially for the fragile and easily contaminated targets. To quantitatively analyze the delivery process, a theoretical model to calculate the acoustic radiation force exerting upon a micro-particle near the boundary in half space is built. An experimental device is also developed to validate the delivery method. A 100 μm diameter micro-silica bead adopted as the delivery target is detached from the upper surface of an aluminum platform and levitated in the fluid. Then, it is transported along the designated path with high precision in horizontal plane. The maximum deviation is only about 3.3 μm. During the horizontal transportation, the levitation of the micro-silica bead is stable, the maximum fluctuation is less than 1 μm. The proposed method may extend the application of acoustic radiation force and provide a promising tool for microstructure or cell manipulation. Copyright © 2014 Elsevier B.V. All rights reserved.

Energy Efficient Cluster Based Scheduling Scheme for Wireless Sensor Networks

PubMed Central

Srie Vidhya Janani, E.; Ganesh Kumar, P.

2015-01-01

The energy utilization of sensor nodes in large scale wireless sensor network points out the crucial need for scalable and energy efficient clustering protocols. Since sensor nodes usually operate on batteries, the maximum utility of network is greatly dependent on ideal usage of energy leftover in these sensor nodes. In this paper, we propose an Energy Efficient Cluster Based Scheduling Scheme for wireless sensor networks that balances the sensor network lifetime and energy efficiency. In the first phase of our proposed scheme, cluster topology is discovered and cluster head is chosen based on remaining energy level. The cluster head monitors the network energy threshold value to identify the energy drain rate of all its cluster members. In the second phase, scheduling algorithm is presented to allocate time slots to cluster member data packets. Here congestion occurrence is totally avoided. In the third phase, energy consumption model is proposed to maintain maximum residual energy level across the network. Moreover, we also propose a new packet format which is given to all cluster member nodes. The simulation results prove that the proposed scheme greatly contributes to maximum network lifetime, high energy, reduced overhead, and maximum delivery ratio. PMID:26495417

Pharmacokinetic studies and anticancer activity of curcumin-loaded nanostructured lipid carriers.

PubMed

Wang, Fengling; Chen, Jin; Dai, Wenting; He, Zhengmin; Zhai, Dandan; Chen, Weidong

2017-09-01

In order to investigate the potential of nanostructured lipid carriers for efficient and targeted delivery of curcumin, the pharmacokinetic parameters of curcumin-loaded nanostructured lipid carriers (Cur-NLC) were evaluated in rats after a single intraperitoneal dose of Cur-NLC. In addition, the anticancer activity of Cur-NLC against human lung adenocarcinoma A549 cells was verified by a cellular uptake study, and a cytotoxicity and apoptosis assay. Bioavailability of Cur-NLC was better than that of native curcumin (p > 0.01), as seen from the area under the plasma concentration-time curve (AUC), maximum plasma concentration (Cmax), mean residence time (MRT) and total plasma clearance (CLz/F). Cur-NLC has a more obvious lung-targeting property in comparison with native curcumin. Cur-NLC showed higher anticancer activity in vitro against A549 cells than native curcumin (IC50 value of 5.66 vs. 9.81 mg L-1, respectively). Meanwhile, Cur-NLC treated A549 cells showed a higher apoptosis rate compared to that of native curcumin. These results indicate that NLC is a promising system for the delivery of curcumin in the treatment of lung adenocarcinoma.

Three dimensional intensity modulated brachytherapy (IMBT): dosimetry algorithm and inverse treatment planning.

PubMed

Shi, Chengyu; Guo, Bingqi; Cheng, Chih-Yao; Esquivel, Carlos; Eng, Tony; Papanikolaou, Niko

2010-07-01

The feasibility of intensity modulated brachytherapy (IMBT) to improve dose conformity for irregularly shaped targets has been previously investigated by researchers by means of using partially shielded sources. However, partial shielding does not fully explore the potential of IMBT. The goal of this study is to introduce the concept of three dimensional (3D) intensity modulated brachytherapy and solve two fundamental issues regarding the application of 3D IMBT treatment planning: The dose calculation algorithm and the inverse treatment planning method. A 3D IMBT treatment planning system prototype was developed using the MATLAB platform. This system consists of three major components: (1) A comprehensive IMBT source calibration method with dosimetric inputs from Monte Carlo (EGSnrc) simulations; (2) a "modified TG-43" (mTG-43) dose calculation formalism for IMBT dosimetry; and (3) a physical constraint based inverse IMBT treatment planning platform utilizing a simulated annealing optimization algorithm. The model S700 Axxent electronic brachytherapy source developed by Xoft, Inc. (Fremont, CA), was simulated in this application. Ten intracavitary accelerated partial breast irradiation (APBI) cases were studied. For each case, an "isotropic plan" with only optimized source dwell time and a fully optimized IMBT plan were generated and compared to the original plan in various dosimetric aspects, such as the plan quality, planning, and delivery time. The issue of the mechanical complexity of the IMBT applicator is not addressed in this study. IMBT approaches showed superior plan quality compared to the original plans and tht isotropic plans to different extents in all studied cases. An extremely difficult case with a small breast and a small distance to the ribs and skin, the IMBT plan minimized the high dose volume V200 by 16.1% and 4.8%, respectively, compared to the original and the isotropic plans. The conformity index for the target was increased by 0.13 and 0.04, respectively. The maximum dose to the skin was reduced by 56 and 28 cGy, respectively, per fraction. Also, the maximum dose to the ribs was reduced by 104 and 96 cGy, respectively, per fraction. The mean dose to the ipsilateral and contralateral breasts and lungs were also slightly reduced by the IMBT plan. The limitations of IMBT are the longer planning and delivery time. The IMBT plan took around 2 h to optimize, while the isotropic plan optimization could reach the global minimum within 5 min. The delivery time for the IMBT plan is typically four to six times longer than the corresponding isotropic plan. In this study, a dosimetry method for IMBT sources was proposed and an inverse treatment planning system prototype for IMBT was developed. The improvement of plan quality by 3D IMBT was demonstrated using ten APBI case studies. Faster computers and higher output of the source can further reduce plan optimization and delivery time, respectively.

Pharmacokinetic modeling of a gel-delivered dapivirine microbicide in humans.

PubMed

Halwes, Michael E; Steinbach-Rankins, Jill M; Frieboes, Hermann B

2016-10-10

Although a number of drugs have been developed for the treatment and prevention of human immunodeficiency virus (HIV) infection, it has proven difficult to optimize the drug and dosage parameters. The vaginal tissue, comprised of epithelial, stromal and blood compartments presents a complex system which challenges evaluation of drug kinetics solely through empirical effort. To provide insight into the underlying processes, mathematical modeling and computational simulation have been applied to the study of retroviral microbicide pharmacokinetics. Building upon previous pioneering work that modeled the delivery of Tenofovir (TFV) via topical delivery to the vaginal environment, here we computationally evaluate the performance of the retroviral inhibitor dapivirine released from a microbicide gel. We adapt the TFV model to simulate the multicompartmental diffusion and uptake of dapivirine into the blood plasma and vaginal compartments. The results show that dapivirine is expected to accumulate at the interface between the gel and epithelium compartments due to its hydrophobic characteristics. Hydrophobicity also results in decreased diffusivity, which may impact distribution by up to 2 orders of magnitude compared to TFV. Maximum concentrations of dapivirine in the epithelium, stroma, and blood were 9.9e7, 2.45e6, and 119pg/mL, respectively. This suggests that greater initial doses or longer time frames are required to obtain higher drug concentrations in the epithelium. These observations may have important ramifications if a specific time frame is required for efficacy, or if a minimum/maximum concentration is needed in the mucus, epithelium, or stroma based on combined efficacy and safety data. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of Nicotine Pharmacokinetics and Subjective Effects following Use of a Novel Nicotine Delivery System.

PubMed

Teichert, Axel; Brossard, Patrick; Felber Medlin, Loyse; Sandalic, Larissa; Franzon, Mikael; Wynne, Chris; Laugesen, Murray; Lüdicke, Frank

2018-03-06

Novel nicotine delivery systems represent an evolving part of the tobacco harm reduction strategy. The pharmacokinetic (PK) profile of nicotine delivered by P3L, a pulmonary nicotine delivery system, and its effects on smoking urges and craving relief in relation to Nicorette inhalator were evaluated. This open-label, ascending nicotine levels study was conducted in 16 healthy smokers. Three different nicotine delivery levels, 50, 80, and 150 µg/puff, delivered by the P3L system were evaluated consecutively on different days after the use of the Nicorette inhalator. Venous nicotine PK, subjective effects, and tolerability were assessed. Geometric least-squares means for maximum plasma nicotine concentration (Cmax), generated by the mixed-effect model for exposure comparison, were 9.7, 11.2, and 9.8 ng/mL for the 50, 80, and 150 µg/puff P3L variants, respectively, compared to 6.1 ng/mL after Nicorette inhalator use. Median time from product use start to Cmax was 7.0 minutes for all P3L, compared to 30.0 minutes for the Nicorette inhalator. Craving reduction was slightly faster than with the Nicorette inhalator as assessed with the visual analog scale craving score. The mean Questionnaire of Smoking Urges -brief total scores did not differ for both products. P3L was well tolerated. At all three nicotine levels tested, the inhalation of the nicotine lactate aerosol delivered with the P3L provided plasma nicotine concentrations higher and faster compared to the Nicorette inhalator. The plasma nicotine concentration-time profile supports a pulmonary route of absorption for P3L compared to the oromucosal absorption of the Nicorette inhalator. The combination of nicotine and lactic acid with the P3L device shows potential over existing nicotine delivery systems by delivering nicotine with kinetics close to published data on conventional cigarettes and without exogenous carrier substances as used in current electronic nicotine delivery systems. Altogether, the PK profile, subjective effects, and safety profile obtained in this study suggest P3L is an innovative nicotine delivery product that will be acceptable to adult smokers as an alternative to cigarettes.

Safety and pharmacokinetics of dapivirine delivery from matrix and reservoir intravaginal rings to HIV-negative women.

PubMed

Nel, Annalene; Smythe, Shanique; Young, Katherine; Malcolm, Karl; McCoy, Clare; Rosenberg, Zeda; Romano, Joseph

2009-08-01

Vaginal microbicides for the prevention of HIV transmission may be an important option for protecting women from infection. Incorporation of dapivirine, a lead candidate nonnucleoside reverse transcriptase inhibitor, into intravaginal rings (IVRs) for sustained mucosal delivery may increase microbicide product adherence and efficacy compared with conventional vaginal formulations. Twenty-four healthy HIV-negative women 18-35 years of age were randomly assigned (1:1:1) to dapivirine matrix IVR, dapivirine reservoir IVR, or placebo IVR. Dapivirine concentrations were measured in plasma and vaginal fluid samples collected at sequential time points over the 33-day study period (28 days of IVR use, 5 days of follow-up). Safety was assessed by pelvic/colposcopic examinations, clinical laboratory tests, and adverse events. Both IVR types were safe and well tolerated with similar adverse events observed in the placebo and dapivirine groups. Dapivirine from both IVR types was successfully distributed throughout the lower genital tract at concentrations over 4 logs greater than the EC50 against wild-type HIV-1 (LAI) in MT4 cells. Maximum concentration (Cmax) and area under the concentration-time curve (AUC) values were significantly higher with the matrix than reservoir IVR. Mean plasma concentrations of dapivirine were <2 ng/mL. These findings suggest that IVR delivery of microbicides is a viable option meriting further study.

Novel, full 3D scintillation dosimetry using a static plenoptic camera.

PubMed

Goulet, Mathieu; Rilling, Madison; Gingras, Luc; Beddar, Sam; Beaulieu, Luc; Archambault, Louis

2014-08-01

Patient-specific quality assurance (QA) of dynamic radiotherapy delivery would gain from being performed using a 3D dosimeter. However, 3D dosimeters, such as gels, have many disadvantages limiting to quality assurance, such as tedious read-out procedures and poor reproducibility. The purpose of this work is to develop and validate a novel type of high resolution 3D dosimeter based on the real-time light acquisition of a plastic scintillator volume using a plenoptic camera. This dosimeter would allow for the QA of dynamic radiation therapy techniques such as intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT). A Raytrix R5 plenoptic camera was used to image a 10 × 10 × 10 cm(3) EJ-260 plastic scintillator embedded inside an acrylic phantom at a rate of one acquisition per second. The scintillator volume was irradiated with both an IMRT and VMAT treatment plan on a Clinac iX linear accelerator. The 3D light distribution emitted by the scintillator volume was reconstructed at a 2 mm resolution in all dimensions by back-projecting the light collected by each pixel of the light-field camera using an iterative reconstruction algorithm. The latter was constrained by a beam's eye view projection of the incident dose acquired using the portal imager integrated with the linac and by physical consideration of the dose behavior as a function of depth in the phantom. The absolute dose difference between the reconstructed 3D dose and the expected dose calculated using the treatment planning software Pinnacle(3) was on average below 1.5% of the maximum dose for both integrated IMRT and VMAT deliveries, and below 3% for each individual IMRT incidences. Dose agreement between the reconstructed 3D dose and a radiochromic film acquisition in the same experimental phantom was on average within 2.1% and 1.2% of the maximum recorded dose for the IMRT and VMAT delivery, respectively. Using plenoptic camera technology, the authors were able to perform millimeter resolution, water-equivalent dosimetry of an IMRT and VMAT plan over a whole 3D volume. Since no moving parts are required in the dosimeter, the incident dose distribution can be acquired as a function of time, thus enabling the validation of static and dynamic radiation delivery with photons, electrons, and heavier ions.

Novel, full 3D scintillation dosimetry using a static plenoptic camera

PubMed Central

Goulet, Mathieu; Rilling, Madison; Gingras, Luc; Beddar, Sam; Beaulieu, Luc; Archambault, Louis

2014-01-01

Purpose: Patient-specific quality assurance (QA) of dynamic radiotherapy delivery would gain from being performed using a 3D dosimeter. However, 3D dosimeters, such as gels, have many disadvantages limiting to quality assurance, such as tedious read-out procedures and poor reproducibility. The purpose of this work is to develop and validate a novel type of high resolution 3D dosimeter based on the real-time light acquisition of a plastic scintillator volume using a plenoptic camera. This dosimeter would allow for the QA of dynamic radiation therapy techniques such as intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT). Methods: A Raytrix R5 plenoptic camera was used to image a 10 × 10 × 10 cm3 EJ-260 plastic scintillator embedded inside an acrylic phantom at a rate of one acquisition per second. The scintillator volume was irradiated with both an IMRT and VMAT treatment plan on a Clinac iX linear accelerator. The 3D light distribution emitted by the scintillator volume was reconstructed at a 2 mm resolution in all dimensions by back-projecting the light collected by each pixel of the light-field camera using an iterative reconstruction algorithm. The latter was constrained by a beam's eye view projection of the incident dose acquired using the portal imager integrated with the linac and by physical consideration of the dose behavior as a function of depth in the phantom. Results: The absolute dose difference between the reconstructed 3D dose and the expected dose calculated using the treatment planning software Pinnacle3 was on average below 1.5% of the maximum dose for both integrated IMRT and VMAT deliveries, and below 3% for each individual IMRT incidences. Dose agreement between the reconstructed 3D dose and a radiochromic film acquisition in the same experimental phantom was on average within 2.1% and 1.2% of the maximum recorded dose for the IMRT and VMAT delivery, respectively. Conclusions: Using plenoptic camera technology, the authors were able to perform millimeter resolution, water-equivalent dosimetry of an IMRT and VMAT plan over a whole 3D volume. Since no moving parts are required in the dosimeter, the incident dose distribution can be acquired as a function of time, thus enabling the validation of static and dynamic radiation delivery with photons, electrons, and heavier ions. PMID:25086549

Hollow waveguide for giant Er:YAG laser pulses transfer

NASA Astrophysics Data System (ADS)

Nemec, Michal; Jelinkova, Helena; Koranda, Petr; Cech, Miroslav; Sulc, Jan; Miyagi, Mitsunobu; Shi, Yi-Wei; Matsuura, Yuji

2004-06-01

Short Er:YAG laser pulses were delivered by a cyclic olefin polymer coated silver hollow glass (COP/Ag) waveguide specially designed for a high power radiation. Er:YAG laser was Q-switched by an electro-optic shutter - LiNbO3 Pockels cell with Brewster angle cut input/output faces. The maximum energy output obtained from this system was 29 mJ with the length of pulse 69 ns corresponding to 420 kW output peak power. The system was working with the repetition rate of 1.5 Hz. A delivery system composed of a lens (f = 40 mm), protector and waveguide with the 700/850 μm diameter and 50 cm or 1 m length. The measured maximum delivered intensity was 86 MW/cm2 what corresponds to the transmission of 78.6 % for whole delivery system. Using of a sealed cap, this delivery system gives a possibility of the contact surgical treatment in many medicine branches, for example ophthalmology, urology or dentistry.

NOTE: Pre-clinical evaluation of respiratory-gated delivery of volumetric modulated arc therapy with RapidArc

NASA Astrophysics Data System (ADS)

Nicolini, Giorgia; Vanetti, Eugenio; Clivio, Alessandro; Fogliata, Antonella; Cozzi, Luca

2010-06-01

A study was carried out to evaluate the possibility of delivering volumetric modulated arc therapy with the RapidArc technology under respiratory-gated conditions. The experiments were performed in the framework of a non-clinically released environment. Plans of six patients, all realized for a single arc, were used for the experiments. The Real-time Position Management™ (RPM) respiratory gating system from Varian was used to generate gate-open signals of different durations. Arcs were delivered applying the different gates creating sequences of beam-hold/beam-on during the dose delivery: the average number of interruptions for a single arc ranged from 0 to 45. Dose prescription was set to 2 Gy and different gate-open periods of 30, 15 and 5 s to keep gantry speed constant at maximum. 5 Gy and 15 Gy doses were then applied to gate-open signals of 5 and 8 s, respectively, to mimic the most challenging conditions of slow gantry rotation and high-frequency interruptions. The 5 and 15 Gy experiments represent dose conditions of clinical interest for stereotactic treatments. For each patient and gating condition, pre-treatment 2D verification measurements were performed using the PTW-729 array in conjunction with the Octavius phantom (PTW, Freiburg); measurements were performed on different days (one per patient, with the complete setup of phantom and detectors every time), while each gating experiment was repeated seven consecutive times for reproducibility (without a new setup of the measurement equipment). Measurements were compared with dose calculations in the treatment planning system (performed without any gating) to appraise the dosimetric impact of the presence of gating and the eventual dependence from the number of interruptions during a single arc. Analysis of machine-registered log files in terms of average deviations between actual and expected positions (from automatic measurements every 50 ms) resulted in mean ΔMU (monitor units) <0.02% for all gating conditions. Δ(Gantry angle) = 0.38 ± 0.01° for 2 Gy (all gate periods), 0.24 ± 0.01° for 5 Gy, and 0.10 ± 0.01° for 15 Gy deliveries. Average deviations for multileaf collimator (MLC) positions (root mean square over all 120 leaves) were 0.45 ± 0.01 mm for 2 Gy (all gate periods), 0.32 ± 0.01 mm for 5 Gy and 0.14 ± 0.01 mm for 15 Gy. Results in terms of dose measurements confirmed that the application of gating to RapidArc delivery does not affect the quality of the dose delivery. With criteria of ΔD = 3%, DTA = 3 mm, the gamma test was passing in a range of 99 to 100% of the measured points for most of the cases (with maximum number of interruptions of about 20 per arc) and from 97 to 98% for the extreme case of 15 Gy and 8 s gate-open signal (corresponding to almost 50 interruptions per arc). In conclusion, RapidArc delivery proved, in a pre-clinical phase and non-clinically released framework, to be reliable and dosimetrically accurate also when applied in conjunction with gating procedures.

Drag reductions obtained by modifying a box-shaped ground vehicle

NASA Technical Reports Server (NTRS)

Saltzman, E. J.; Meyer, R. R., Jr.; Lux, D. P.

1974-01-01

A box-shaped ground vehicle was used to simulate the aerodynamic drag of high volume transports, that is, delivery vans, trucks, or motor homes. The coast-down technique was used to define the drag of the original vehicle, having all square corners, and several modifications of the vehicle. Test velocities ranged up to 65 miles per hour, which provided maximum Reynolds numbers of 1 times 10 to the 7th power based on vehicle length. One combination of modifications produced a reduction in aerodynamic drag of 61 percent as compared with the original square-cornered vehicle.

Development, qualification, and delivery of a hydrogen burnoff igniter

NASA Technical Reports Server (NTRS)

Ray, D.

1981-01-01

The hydrogen burnoff igniter, a pyrotechnic device used to burn off excess hydrogen gas near the Space Shuttle Main Engine (SSME) nozzle, was designed, fabricated, and qualified. Characteristics of the burnoff igniter include a function time of 8 + or - 2 seconds, a minimum three foot flame length at maximum output, and hot particles projected 15 feet when fired directly into or perpendicular to a 34.5 knot wind. The three foot flame length was considered to be of questionable importance, since the hot particles are the media for igniting the hydrogen. Flame temperature is greater than 1500 F.

Silica-iron oxide magnetic nanoparticles modified for gene delivery: a search for optimum and quantitative criteria.

PubMed

Mykhaylyk, Olga; Sobisch, Titus; Almstätter, Isabella; Sanchez-Antequera, Yolanda; Brandt, Sabine; Anton, Martina; Döblinger, Markus; Eberbeck, Dietmar; Settles, Marcus; Braren, Rickmer; Lerche, Dietmar; Plank, Christian

2012-05-01

To optimize silica-iron oxide magnetic nanoparticles with surface phosphonate groups decorated with 25-kD branched polyethylenimine (PEI) for gene delivery. Surface composition, charge, colloidal stabilities, associations with adenovirus, magneto-tranduction efficiencies, cell internalizations, in vitro toxicities and MRI relaxivities were tested for the particles decorated with varying amounts of PEI. Moderate PEI-decoration of MNPs results in charge reversal and destabilization. Analysis of space and time resolved concentration changes during centrifugation clearly revealed that at >5% PEI loading flocculation gradually decreases and sufficient stabilization is achieved at >10%. The association with adenovirus occurred efficiently at levels over 5% PEI, resulting in the complexes stable in 50% FCS at a PEI-to-iron w/w ratio of ≥7%; the maximum magneto-transduction efficiency was achieved at 9-12% PEI. Primary silica iron oxide nanoparticles and those with 11.5% PEI demonstrated excellent r(2)* relaxivity values (>600 s(-1)(mM Fe)(-1)) for the free and cell-internalized particles. Surface decoration of the silica-iron oxide nanoparticles with a PEI-to-iron w/w ratio of 10-12% yields stable aqueous suspensions, allows for efficient viral gene delivery and labeled cell detection by MRI.

Randomized controlled trial on the effects of training in the use of closed-circuit television on reading performance.

PubMed

Burggraaff, Marloes C; van Nispen, Ruth M A; Hoeben, Frank P; Knol, Dirk L; van Rens, Ger H M B

2012-04-24

To investigate the effectiveness of training in the use of closed-circuit television (CCTV) on reading performance in visually impaired patients. In a multicenter masked randomized controlled trial, 122 patients were randomized either to a treatment group that received usual delivery instructions from the CCTV supplier combined with concise outpatient standardized training, or to a control group that received delivery instructions only. The main outcome measure was reading performance, which was obtained by measuring reading acuity, reading speed, reading errors, column-tracking time, and technical reading, approximately two weeks after patients had received their CCTV and 3 months later. Videotapes of all measurements were rated by two investigators. Training effects were analyzed with linear mixed modeling. There were no statistically significant differences in results between the treatment and control group. However, introducing a CCTV increased reading acuity (mean difference [MD] 0.93 logRAD; P < 0.01) and maximum reading speed (MD 15 wpm; P < 0.01), and decreased the number of errors (MD 0.33; P = 0.04), compared to reading without CCTV. Average reading speed (P = 0.05), number of errors (P = 0.04), and column-tracking time (P = 0.01) improved over time. Prescribing a CCTV and the delivery instructions by the supplier seemed sufficient to improve reading performance. Additional training in the use of this device did not result in further improvement. Based on these results, outpatient low-vision rehabilitation centers may consider reallocating part of the training resources into other evidence-based rehabilitation programs. (trialregister.nl number, NTR1031.).

Feasibility Study for Markerless Tracking of Lung Tumors in Stereotactic Body Radiotherapy

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

Richter, Anne, E-mail: richter_a3@klinik.uni-wuerzburg.d; Wilbert, Juergen; Baier, Kurt

2010-10-01

Purpose: To evaluate the feasibility and accuracy of a method for markerless tracking of lung tumors in electronic portal imaging device (EPID) movies and to analyze intra- and interfractional variations in tumor motion. Methods and Materials: EPID movies were acquired during stereotactic body radiotherapy (SBRT) given to 40 patients with 49 pulmonary targets and retrospectively analyzed. Tumor visibility and tracking accuracy were determined by three observers. Tumor motion of 30 targets was analyzed in detail via four-dimensional computed tomography (4DCT) and EPID in the superior-inferior direction for intra- and interfractional variations. Results: Tumor visibility was sufficient for markerless tracking inmore » 47% of the EPID movies. Tumor size and visibility in the DRR were correlated with visibility in the EPID images. The difference between automatic and manual tracking was a maximum of 2 mm for 98.3% in the x direction and 89.4% in the y direction. Motion amplitudes in 4DCT images (range, 0.7-17.9 mm; median, 4.9 mm) were closely correlated with amplitudes in the EPID movies. Intrafractional and interfractional variability of tumor motion amplitude were of similar magnitude: 1 mm on average to a maximum of 4 mm. A change in moving average of more than {+-}1 mm, {+-}2 mm, and {+-}4 mm were observed in 47.1%, 17.1%, and 4.5% of treatment time for all trajectories, respectively. Mean tumor velocity was 3.4 mm/sec, to a maximum 61 mm/sec. Conclusions: Tracking of pulmonary tumors in EPID images without implanted markers was feasible in 47% of all treatment beams. 4DCT is representative of the evaluation of mean breathing motion on average, but larger deviations occurred in target motion between treatment planning and delivery effort a monitoring during delivery.« less

Fluoride loaded polymeric nanoparticles for dental delivery.

PubMed

Nguyen, Sanko; Escudero, Carlos; Sediqi, Nadia; Smistad, Gro; Hiorth, Marianne

2017-06-15

The overall aim of the present paper was to develop fluoride loaded nanoparticles based on the biopolymers chitosan, pectin, and alginate, for use in dental delivery. First, the preparation of nanoparticles in the presence of sodium fluoride (NaF) as the active ingredient by ionic gelation was investigated followed by an evaluation of their drug entrapment and release properties. Chitosan formed stable, spherical, and monodisperse nanoparticles in the presence of NaF and tripolyphoshate as the crosslinker, whereas alginate and pectin were not able to form any definite nanostructures in similar conditions. The fluoride loading capacity was found to be 33-113ppm, and the entrapment efficiency 3.6-6.2% for chitosan nanoparticles prepared in 0.2-0.4% (w/w) NaF, respectively. A steady increase in the fluoride release was observed for chitosan nanoparticles prepared in 0.2% NaF both in pH5 and 7 until it reached a maximum at time point 4h and maintained at this level for at least 24h. Similar profiles were observed for formulations prepared in 0.4% NaF; however the fluoride was released at a higher level at pH5. The low concentration, but continuous delivery of fluoride from the chitosan nanoparticles, with possible expedited release in acidic environment, makes these formulations highly promising as dental delivery systems in the protection against caries development. Copyright © 2017 Elsevier B.V. All rights reserved.

Surface temperature and thermal penetration depth of Nd:YAG laser applied to enamel and dentin

NASA Astrophysics Data System (ADS)

White, Joel M.; Neev, Joseph; Goodis, Harold E.; Berns, Michael W.

1992-06-01

The determination of the thermal effects of Nd:YAG laser energy on enamel and dentin is critical in understanding the clinical applications of caries removal and surface modification. Recently extracted non-carious third molars were sterilized with gamma irradiation. Calculus and cementum were removed using scaling instruments and 600 grit sand paper. The smear layer produced by sanding was removed with a solution of 0.5 M EDTA (pH 7.4) for two minutes. Enamel and dentin surfaces were exposed to a pulsed Nd:YAG laser with 150 microsecond(s) pulse duration. Laser energy was delivered to the teeth with a 320 micrometers diameter fiberoptic delivery system, for exposure times of 1, 10 and 30 seconds. Laser parameters varied from 0.3 to 3.0 W, 10 to 30 Hz and 30 to 150 mJ/pulse. Other conditions included applications of hot coffee, carbide bur in a dental air-cooled turbine drill and soldering iron. Infrared thermography was used to measure the maximum surface temperature on, and thermal penetration distance into enamel and dentin. Thermographic data were analyzed with a video image processor to determine the diameter of maximum surface temperature and thermal penetration distance of each treatment. Between/within statistical analysis of variance (p

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

PubMed Central

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

2014-01-01

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

Noncoplanar VMAT for nasopharyngeal tumors: Plan quality versus treatment time

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

Wild, Esther, E-mail: e.wild@dkfz.de; Bangert, Mark; Nill, Simeon

Purpose: The authors investigated the potential of optimized noncoplanar irradiation trajectories for volumetric modulated arc therapy (VMAT) treatments of nasopharyngeal patients and studied the trade-off between treatment plan quality and delivery time in radiation therapy. Methods: For three nasopharyngeal patients, the authors generated treatment plans for nine different delivery scenarios using dedicated optimization methods. They compared these scenarios according to dose characteristics, number of beam directions, and estimated delivery times. In particular, the authors generated the following treatment plans: (1) a 4π plan, which is a not sequenced, fluence optimized plan that uses beam directions from approximately 1400 noncoplanar directionsmore » and marks a theoretical upper limit of the treatment plan quality, (2) a coplanar 2π plan with 72 coplanar beam directions as pendant to the noncoplanar 4π plan, (3) a coplanar VMAT plan, (4) a coplanar step and shoot (SnS) plan, (5) a beam angle optimized (BAO) coplanar SnS IMRT plan, (6) a noncoplanar BAO SnS plan, (7) a VMAT plan with rotated treatment couch, (8) a noncoplanar VMAT plan with an optimized great circle around the patient, and (9) a noncoplanar BAO VMAT plan with an arbitrary trajectory around the patient. Results: VMAT using optimized noncoplanar irradiation trajectories reduced the mean and maximum doses in organs at risk compared to coplanar VMAT plans by 19% on average while the target coverage remains constant. A coplanar BAO SnS plan was superior to coplanar SnS or VMAT; however, noncoplanar plans like a noncoplanar BAO SnS plan or noncoplanar VMAT yielded a better plan quality than the best coplanar 2π plan. The treatment plan quality of VMAT plans depended on the length of the trajectory. The delivery times of noncoplanar VMAT plans were estimated to be 6.5 min in average; 1.6 min longer than a coplanar plan but on average 2.8 min faster than a noncoplanar SnS plan with comparable treatment plan quality. Conclusions: The authors’ study reconfirms the dosimetric benefits of noncoplanar irradiation of nasopharyngeal tumors. Both SnS using optimized noncoplanar beam ensembles and VMAT using an optimized, arbitrary, noncoplanar trajectory enabled dose reductions in organs at risk compared to coplanar SnS and VMAT. Using great circles or simple couch rotations to implement noncoplanar VMAT, however, was not sufficient to yield meaningful improvements in treatment plan quality. The authors estimate that noncoplanar VMAT using arbitrary optimized irradiation trajectories comes at an increased delivery time compared to coplanar VMAT yet at a decreased delivery time compared to noncoplanar SnS IMRT.« less

SU-E-J-194: Continuous Patient Surface Monitoring and Motion Analysis During Lung SBRT

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

Chung, E; Rioux, A; Benedict, S

2015-06-15

Purpose: Continuous monitoring of the SBRT lung patient motion during delivery is critical for ensuring adequate target volume margins in stereotactic body radiotherapy (SBRT). This work assesses the deviation of the patient surface motion using a real-time surface tracking system throughout treatment delivery. Methods: Our SBRT protocol employs abdominal compression to reduce the diaphragm movement to within 1 cm, and this is confirmed daily with fluoroscopy. Most patients are prescribed 3–5 fractions, and on treatment day a repeat motion analysis with fluoroscopy is performed, followed by a kV CBCT is aligned with the original planning CT image for 3D setupmore » confirmation. During this entire process a patient surface data restricted to whole chest or the sternum at the middle of the breathing cycle was captured using AlignRT optical surface tracking system and defined as a reference surface. For 10 patients, the deviation of the patient position from the reference surface was recorded during the SBRT delivery in the anterior-posterior (AP) direction at 3–6 measurements per second. Results: On average, the patient position deviated from the reference surface more than 4 mm, 3 mm and 2 mm in the AP direction for 0.95%, 3.7% and 11.1% of the total treatment time, respectively. Only one of the 10 patients showed that the maximum deviation of the patient surface during the SBRT delivery was greater than 1 cm. The average deviation of the patient surface from the reference surface during the SBRT delivery was not greater than 1.6 mm for any patient. Conclusion: This investigation indicates that AP motion can be significant even though the frequency is low. Continuous monitoring during SBRT has demonstrated value in monitoring patient motion ensuring that margins selected for SBRT are appropriate, and the use of non-ionizing and high-frequency imaging can provide useful indicators of motion during treatment.« less

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. DDF values agreed within 0.3 ± 0.1 mm, with a maximum deviation of 0.6 mm. For the scanned proton pencil beams, Zebra and Bragg peak chamber range values demonstrated agreement of 0.0 ± 0.3 mm with a maximum deviation of 1.3 mm. The setup and measurement time for all Zebra measurements was 3 and 20 times less, respectively, compared to the water tank measurements.Conclusions: Our investigation shows that the Zebra can be useful not only for fast but also for accurate measurements of the depth-dose distributions of both scattered and scanned proton beams. The analysis of a large set of measurements shows that the commonly assessed beam quality parameters obtained with the Zebra are within the acceptable variations specified by the manufacturer for our delivery system.« less

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

Maurer, J; Sintay, B; Manning, M

Purpose: This study evaluates a novel algorithm that can be used with any treatment planning system for simple and rapid generation of stereotactic radiosurgery (SRS) plans for treating multiple brain metastases using a single isocenter dynamic conformal arc (DCA) approach. This technique is compared with a single isocenter volumetric modulated arc therapy (VMAT) technique in terms of delivery time, conformity, low dose spread and delivery accuracy. Methods: Five patients, with a total of 37 (5 – 11) targets were planned using a previously published method for generating optimal VMAT plans and using the proposed DCA algorithm. All planning target volumesmore » (PTVs) were planned to 20 Gy, meeting a minimum 99% coverage and maximum 135 % hot spot for both techniques. Quality assurance was performed using radiochromic film, with films placed in the high dose regions of each PTV. Normal tissue volumes receiving 12 Gy and 6 Gy (V12 and V6) were computed for each plan. Conformity index (CI) and gamma evaluations (95% of points passing 4%/0.5mm) were computed for each PTV. Results: Delivery times, including beam on and table rotation times, were comparable: 17 – 22 minutes for all deliveries. V12s for DCA plans were (18.5±15.2 cc) vs. VMAT (19.7±14.4 cc). V6s were significantly lower for DCA (69.0±52.0 cc) compared with VMAT (154.0±91.0 cc) (p <<0.05). CIs for VMAT targets were (1.38±0.50) vs. DCA (1.61±0.41). 36 of 37 DCA planned targets passed gamma tests, while 29 of 37 VMAT planned targets passed. Conclusion: Single isocenter DCA plans were easily achieved. The evaluation suggests that DCA may represent a favorable technique compared with VMAT for multiple target SRS by reducing dose to normal tissue and more accurately depicting deliverable dose.« less

Biodistribution of biodegradable polymeric nano-carriers loaded with busulphan and designed for multimodal imaging.

PubMed

Asem, Heba; Zhao, Ying; Ye, Fei; Barrefelt, Åsa; Abedi-Valugerdi, Manuchehr; El-Sayed, Ramy; El-Serafi, Ibrahim; Abu-Salah, Khalid M; Hamm, Jörg; Muhammed, Mamoun; Hassan, Moustapha

2016-12-19

Multifunctional nanocarriers for controlled drug delivery, imaging of disease development and follow-up of treatment efficacy are promising novel tools for disease diagnosis and treatment. In the current investigation, we present a multifunctional theranostic nanocarrier system for anticancer drug delivery and molecular imaging. Superparamagnetic iron oxide nanoparticles (SPIONs) as an MRI contrast agent and busulphan as a model for lipophilic antineoplastic drugs were encapsulated into poly (ethylene glycol)-co-poly (caprolactone) (PEG-PCL) micelles via the emulsion-evaporation method, and PEG-PCL was labelled with VivoTag 680XL fluorochrome for in vivo fluorescence imaging. Busulphan entrapment efficiency was 83% while the drug release showed a sustained pattern over 10 h. SPION loaded-PEG-PCL micelles showed contrast enhancement in T 2 *-weighted MRI with high r 2 * relaxivity. In vitro cellular uptake of PEG-PCL micelles labeled with fluorescein in J774A cells was found to be time-dependent. The maximum uptake was observed after 24 h of incubation. The biodistribution of PEG-PCL micelles functionalized with VivoTag 680XL was investigated in Balb/c mice over 48 h using in vivo fluorescence imaging. The results of real-time live imaging were then confirmed by ex vivo organ imaging and histological examination. Generally, PEG-PCL micelles were highly distributed into the lungs during the first 4 h post intravenous administration, then redistributed and accumulated in liver and spleen until 48 h post administration. No pathological impairment was found in the major organs studied. Thus, with loaded contrast agent and conjugated fluorochrome, PEG-PCL micelles as biodegradable and biocompatible nanocarriers are efficient multimodal imaging agents, offering high drug loading capacity, and sustained drug release. These might offer high treatment efficacy and real-time tracking of the drug delivery system in vivo, which is crucial for designing of an efficient drug delivery system.

Comparative analysis of SmartArc‐based dual arc volumetric‐modulated arc radiotherapy (VMAT) versus intensity‐modulated radiotherapy (IMRT) for nasopharyngeal carcinoma

PubMed Central

Chao, Pei‐Ju; Ting, Hui‐Min; Lo, Su‐Hua; Wang, Yu‐Wen; Tuan, Chiu‐Ching; Fang, Fu‐Min

2011-01-01

The purpose of this study was to evaluate and quantify the planning performance of SmartArc‐based volumetric‐modulated arc radiotherapy (VMAT) versus fixed‐beam intensity‐modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) using a sequential mode treatment plan. The plan quality and performance of dual arc‐VMAT (DA‐VMAT) using the Pinnacle3 Smart‐Arc system (clinical version 9.0; Philips, Fitchburg, WI, USA) were evaluated and compared with those of seven‐field (7F)‐IMRT in 18 consecutive NPC patients. Analysis parameters included the conformity index (CI) and homogeneity index (HI) for the planning target volume (PTV), maximum and mean dose, normal tissue complication probability (NTCP) for the specified organs at risk (OARs), and comprehensive quality index (CQI) for an overall evaluation in the 11 OARs. Treatment delivery time, monitor units per fraction (MU/fr), and gamma (Γ3mm,3%) evaluations were also analyzed. DA‐VMAT achieved similar target coverage and slightly better homogeneity than conventional 7F‐IMRT with a similar CI and HI. NTCP values were only significantly lower in the left parotid gland (for xerostomia) for DA‐VMAT plans. The mean value of CQI at 0.98±0.02 indicated a 2% benefit in sparing OARs by DA‐VMAT. The MU/fr used and average delivery times appeared to show improved efficiencies in DA‐VMAT. Each technique demonstrated high accuracy in dose delivery in terms of a high‐quality assurance (QA) passing rate (>98%) of the (Γ3mm,3%) criterion. The major difference between DA‐VMAT and 7F‐IMRT using a sequential mode for treating NPC cases appears to be improved efficiency, resulting in a faster delivery time and the use of fewer MU/fr. PACS number: 87.53.Tf, 87.55.x, 87.55.D, 87.55.dk PMID:22089015

Effect of ambient temperature and air pollutants on the risk of preterm birth, Rome 2001-2010.

PubMed

Schifano, Patrizia; Lallo, Adele; Asta, Federica; De Sario, Manuela; Davoli, Marina; Michelozzi, Paola

2013-11-01

Although the prevalence of preterm births ranges from 5 to 13% and represents the leading cause of perinatal mortality and morbidity in developed countries, the etiology of preterm birth remains uncertain. We aimed to evaluate the effect of short-term exposure to high and low temperatures and air pollution on preterm delivery and to identify socio-demographic and clinical maternal risk factors enhancing individual susceptibility. We analyzed all singleton live births by natural delivery that occurred in Rome in 2001-2010. A time-series approach was used to estimate the effect of exposure to minimum temperature, maximum apparent temperature, heat waves, particulate matter with an aerodynamic diameter of 10μm or less (PM10), ozone, and nitrogen dioxide in the month preceding delivery; the analysis was conducted separately for cold and warm seasons. Socio-demographic and clinical risk factors were included as interaction terms. Preterm births comprised nearly 6% of our cohort. An increase of 1.9% (95% confidence interval (CI) 0.86-2.87) in daily preterm births per 1°C increase in maximum apparent temperature in the 2days preceding delivery was estimated for the warm season. Older women, women with higher education levels, and women with obstetric or chronic pathologies reported during delivery had a lower effect of temperature on the risk of preterm birth, while women with a chronic disease in the two years before delivery and mothers<20years showed a higher effect. A +19% (95% CI 7.91-31.69) increase in preterm births was observed during heat waves. Temperature had no effect during the cold season. We detected a significant effect of PM10 on preterm-birth risk at a lag period of 12-22days during the warm season (+0.69%; 95% CI 0.23-1.15, for 1μg/m(3) increase of pollutant); women with obstetric pathologies and with a higher education level showed a higher risk. Our results suggest a possible short-term effect of heat and a more delayed and prolonged effect of PM10 exposure on preterm-birth risk, as well as the existence of more susceptible subgroups of women. Our observations support the few reported investigations, and may help to increase awareness among public-health stakeholders and clinicians regarding the role of these environmental exposures as risk factors for premature birth and health consequences for children later in life. © 2013.

SU-F-BRE-16: VMAT Commissioning and Quality Assurance (QA) of An Elekta Synergy-STM Linac Using ICOM Test HarnessTM

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

Nguyen, A; Ironwood CRC, Phoenix, AZ; Rajaguru, P

2014-06-15

Purpose: To establish a set of tests based on the iCOM software that can be used to commission and perform periodic QA of VMAT delivery on the Elekta Synergy-S, commonly known as the Beam Modulator (BM). Methods: iCOM is used to create and deliver customized treatment fields to characterize the system in terms of 1) MLC positioning accuracy under static and dynamic delivery with full gantry rotation, 2) MLC positioning with known errors, 3) Maximum dose rate, 4) Maximum MLC speed, 5) Maximum gantry speed, 6) Synchronization: gantry speed versus dose rate, and 7) Synchronization: MLC speed versus dose rate.more » The resulting images were captured on the iView GT and exported in DICOM format to Dosimetry Check™ system for visual and quantitative analysis. For the initial commissioning phase, the system tests described should be supplemented with extensive patient QAs covering all clinically relevant treatment sites. Results: The system performance test suite showed that on our Synergy-S, MLC positioning was accurate under both static and dynamic deliveries. Intentional errors of 1 mm were also easily identified on both static and dynamic picket fence tests. Maximum dose rate was verified with stop watch to be consistently between 475-480 MU/min. Maximum gantry speed and MLC speed were 5.5 degree/s and 2.5 cm/s respectively. After accounting for beam flatness, both synchronization tests, gantry versus dose rate and MLC speed versus dose rate, were successful as the fields were uniform across the strips and there were no obvious cold/hot spots. Conclusion: VMAT commissioning and quality assurance should include machine characterization tests in addition to patient QAs. Elekta iCOM is a valuable tool for the design of customized VMAT field with specific MU, MLC leaf positions, dose rate, and indirect control of MLC and gantry speed at each of its control points.« less

Dosimetric and delivery efficiency investigation for treating hepatic lesions with a MLC-equipped robotic radiosurgery-radiotherapy combined system.

PubMed

Jin, Lihui; Price, Robert A; Wang, Lu; Meyer, Joshua; Fan, James Jiajin; Ma, Chang Ming Charlie

2016-02-01

The CyberKnife M6 (CK-M6) Series introduced a multileaf collimator (MLC) for extending its capability from stereotactic radiosurgery/stereotactic radiotherapy (SBRT) to conventionally fractionated radiotherapy. This work is to investigate the dosimetric quality of plans that are generated using MLC-shaped beams on the CK-M6, as well as their delivery time, via comparisons with the intensity modulated radiotherapy plans that were clinically used on a Varian Linac for treating hepatic lesions. Nine patient cases were selected and divided into three groups with three patients in each group: (1) the group-one patients were treated conventionally (25 fractions); (2) the group-two patients were treated with SBRT-like hypofractionation (5 fractions); and (3) the group-three patients were treated similar to group-one patients, but with two planning target volumes (PTVs) and two different prescription dose levels correspondingly. The clinically used plans were generated on the eclipse treatment planning system (TPS) and delivered on a Varian Linac (E-V plans). The multiplan (MP) TPS was used to replan these clinical cases with the MLC as the beam device for the CK-M6 (C-M plans). After plans were normalized to the same PTV dose coverage, comparisons between the C-M and E-V plans were performed based on D(99%) (percentage of prescription dose received by 99% of the PTV), D(0.1cm(3)) (the percentage of prescription dose to 0.1 cm(3) of the PTV), and doses received by critical structures. Then, the delivery times for the C-M plans will be obtained, which are the MP TPS generated estimations assuming having an imaging interval of 60 s. The difference in D(99%) between C-M and E-V plans is +0.6% on average (+ or - indicating a higher or lower dose from C-M plans than from E-V plans) with a range from -4.1% to +3.8%, and the difference in D(0.1cm(3)) was -1.0% on average with a range from -5.1% to +2.9%. The PTV conformity index (CI) for the C-M plans ranges from 1.07 to 1.29 with a mean of 1.19, slightly inferior to the E-V plans, in which the CI ranges from 1.00 to 1.15 with a mean of 1.07. Accounting for all nine patients in three groups, 45% of the critical structures received a lower mean dose for the C-M plans as compared with the E-V plans, and similarly, 48% received a lower maximum dose. Furthermore, the average difference of the mean critical structure dose between the C-M and E-V plans over all critical structures for all patients showed only +2.10% relative to the prescription dose and the similar comparison finds the average difference of the maximum critical structure dose of only +1.24%. The estimated delivery times for the C-M plans on the CK-M6 range from 18 to 24 minutes while they are from 7 to 13.7 min for the E-V plans on the Varian Linac. For treating hepatic lesions, for the C-M plans that are comparable to E-V plans in quality, the times needed to deliver these C-M plans on the CK-M6 are longer than the delivery time for the E-V plans on the Varian Linac, but may be clinically acceptable.

Indications for Cesarean Delivery in Mexico: Evaluation of Appropriate Use and Justification.

PubMed

Aranda-Neri, Juan Carlos; Suárez-López, Leticia; DeMaria, Lisa M; Walker, Dilys

2017-03-01

Cesarean delivery is one of the most widely used surgical interventions in Latin America and in many cases it is performed with no clear medical indication. Our objective was to analyze the relationship between reported indications for a cesarean and support for that indication in the clinical record in four Mexican hospitals, during the 2006-2007 period. The data are from 604 (37.1%) women from a total of 1,625 who were admitted to the hospital in labor, and who gave birth through cesarean. Multivariate logistical regression analysis was used to explore the association between indications for clinically justified or unjustified surgery and other clinical and sociodemographic variables. Supporting clinical information for indications of cesarean delivery were found in only 45 percent of the cases considered. The adjusted statistical analysis showed that the variables associated with an unjustified indication for cesarean were: not having had a prior birth (OR 1.84 [95% CI 1.16-2.89]), having a maximum cervical dilation of 4 centimeters or less at time of cesarean (OR 2.44 [95% CI 1.53-3.87]), and having received care in a private hospital (OR 6.11 [95% CI 1.90-19.57]). The indications for cesarean related to labor dynamics were those least supported. Not having had a prior birth poses the greatest risk of having a poorly supported indication for a cesarean delivery. It would be prudent to institute audits, and greater requirements for and surveillance of documentation for cesarean delivery indications. © 2016 Wiley Periodicals, Inc.

Atmospheric moisture transport to western North America during the Last Glacial Maximum and deglaciation

NASA Astrophysics Data System (ADS)

Lora, J. M.; Mitchell, J.; Risi, C.; Tripati, A.

2016-12-01

Proxy reconstructions of the paleoclimate of western North America indicate that the southwest was considerably wetter during the Last Glacial Maximum (LGM; 21 ka) than in the present, while the Pacific Northwest received substantially less rainfall. Pluvial paleolake systems existed in regions that today are arid, from the Great Basin down to the modern Mojave Desert. Many lakes grew to highstands during the early deglaciation, before quickly falling to near-modern levels of dryness around 15 ka, around the same time when moisture in the northwest increased. The timing and distribution of these shifts observed in hydroclimate proxies have been hypothesized to reflect changes in the position of the polar jet stream or the seasonality of precipitation, but the source and delivery processes of the water feeding these regions are debated. Using results from a range of climate models and reanalyses, we explore the role of atmospheric rivers in delivering water to western North America during the glacial, as well as the evolution of water delivery during the deglaciation. Due to the presence of continental ice sheets, deepened Aleutian Low and weakened North Pacific High pressure systems concentrated water transport in atmospheric rivers into California relative to the present, enhancing moisture and precipitation in the southwest and shifting it away from the northwest. As the ice sheets receded, a rapid reorganization of the atmospheric circulation, accompanied by abrupt changes of the semi-permanent pressure systems, precipitated drying and moistening of southwestern and northwestern North America, respectively. We find that during this interval, changes in the water budget of western North America are attributable to the intensity of moisture transport into the continent, and not to the position of the jet stream.

Efficient Interplay Effect Mitigation for Proton Pencil Beam Scanning by Spot-Adapted Layered Repainting Evenly Spread out Over the Full Breathing Cycle.

PubMed

Poulsen, Per Rugaard; Eley, John; Langner, Ulrich; Simone, Charles B; Langen, Katja

2018-01-01

To develop and implement a practical repainting method for efficient interplay effect mitigation in proton pencil beam scanning (PBS). A new flexible repainting scheme with spot-adapted numbers of repainting evenly spread out over the whole breathing cycle (assumed to be 4 seconds) was developed. Twelve fields from 5 thoracic and upper abdominal PBS plans were delivered 3 times using the new repainting scheme to an ion chamber array on a motion stage. One time was static and 2 used 4-second, 3-cm peak-to-peak sinusoidal motion with delivery started at maximum inhalation and maximum exhalation. For comparison, all dose measurements were repeated with no repainting and with 8 repaintings. For each motion experiment, the 3%/3-mm gamma pass rate was calculated using the motion-convolved static dose as the reference. Simulations were first validated with the experiments and then used to extend the study to 0- to 5-cm motion magnitude, 2- to 6-second motion periods, patient-measured liver tumor motion, and 1- to 6-fraction treatments. The effect of the proposed method was evaluated for the 5 clinical cases using 4-dimensional (4D) dose reconstruction in the planning 4D computed tomography scan. The target homogeneity index, HI = (D 2 - D 98 )/D mean , of a single-fraction delivery is reported, where D 2 and D 98 is the dose delivered to 2% and 98% of the target, respectively, and D mean is the mean dose. The gamma pass rates were 59.6% ± 9.7% with no repainting, 76.5% ± 10.8% with 8 repaintings, and 92.4% ± 3.8% with the new repainting scheme. Simulations reproduced the experimental gamma pass rates with a 1.3% root-mean-square error and demonstrated largely improved gamma pass rates with the new repainting scheme for all investigated motion scenarios. One- and two-fraction deliveries with the new repainting scheme had gamma pass rates similar to those of 3-4 and 6-fraction deliveries with 8 repaintings. The mean HI for the 5 clinical cases was 14.2% with no repainting, 13.7% with 8 repaintings, 12.0% with the new repainting scheme, and 11.6% for the 4D dose without interplay effects. A novel repainting strategy for efficient interplay effect mitigation was proposed, implemented, and shown to outperform conventional repainting in experiments, simulations, and dose reconstructions. This strategy could allow for safe and more optimal clinical delivery of thoracic and abdominal proton PBS and better facilitate hypofractionated and stereotactic treatments. Copyright © 2017 Elsevier Inc. All rights reserved.

Liposomal Drug Delivery System for Cancer Therapy: Advancement and Patents.

PubMed

Jha, Sheetal; Sharma, Pramod K; Malviya, Rishabha

2016-01-01

In this review article, authors reviewed about the liposomes which are amongst various drug delivering systems for the delivery of the therapeutic agents at the target site. Advances in liposomal drug delivery systems for the cancer therapy have enhanced the therapeutic levels of the anticancer moieties. Liposomes show promising action on the tumor by incorporating less amount of drug at the target site, with minimum toxic effect and maximum therapeutic effect and thereby enhancing the bioavailability. Liposome-based drug delivery systems provide the potential to elevate the effect of drug concentration in tumor cells. Manuscript briefly describes the role of liposomes in cancer therapy and various patents based on the same. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

SU-E-J-169: The Dosimetric and Temporal Effects of Respiratory-Gated Radiation Therapy in Lung Cancer Patients

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

Rouabhi, O; Gross, B; Xia, J

2015-06-15

Purpose: To evaluate the dosimetric and temporal effects of high dose rate treatment mode for respiratory-gated radiation therapy in lung cancer patients. Methods: Treatment plans from five lung cancer patients (3 nongated (Group 1), 2 gated at 80EX-80IN (Group 2)) were retrospectively evaluated. The maximum tumor motions range from 6–12 mm. Using the same planning criteria, four new treatment plans, corresponding to four gating windows (20EX–20IN, 40EX–40IN, 60EX–60IN, and 80EX–80IN), were generated for each patient. Mean tumor dose (MTD), mean lung dose (MLD), and lung V20 were used to assess the dosimetric effects. A MATLAB algorithm was developed to computemore » treatment time by considering gantry rotation time, time to position collimator leaves, dose delivery time (scaled relative to the gating window), and communication overhead. Treatment delivery time for each plan was estimated using a 500 MU/min dose rate for the original plans and a 1500 MU/min dose rate for the gated plans. Results: Differences in MTD were less than 1Gy across plans for all five patients. MLD and lung V20 were on average reduced between −16.1% to −6.0% and −20.0% to −7.2%, respectively for non-gated plans when compared with the corresponding gated plans, and between − 5.8% to −4.2% and −7.0% to −5.4%, respectively for plans originally gated at 80EX–80IN when compared with the corresponding 20EX-20IN to 60EX– 60IN gated plans. Treatment delivery times of gated plans using high dose rate were reduced on average between −19.7% (−1.9min) to −27.2% (−2.7min) for originally non-gated plans and −15.6% (−0.9min) to −20.3% (−1.2min) for originally 80EX-80IN gated plans. Conclusion: Respiratory-gated radiation therapy in lung cancer patients can reduce lung toxicity, while maintaining tumor dose. Using a gated high-dose-rate treatment, delivery time comparable to non-gated normal-dose-rate treatment can be achieved. This research is supported by Siemens Medical Solutions USA, Inc.« less

Characterization of critical physical and mechanical properties of freeze-dried grape powder for development of a clinical patient delivery system.

PubMed

Hu, Daniel; Haware, Rahul V; Hamad, Mazen L; Morris, Kenneth R

2013-02-01

Grapes are hypothesized to be a "food medicine." Freeze-dried grape powder (FDGP) is being used to test clinical activity for a variety of applications and a reproducible and reliable delivery system was required. The FDGP was characterized using traditional physico-chemical methods to generate the data needed to identify its primary liability, i.e. moisture sorption. Above a threshold level of moisture content (~25% w/w, at RT), the material becomes both difficult to handle and exhibits significant degradation of several potentially clinically important chemical components (catechin, epicatechin, resveratrol). A moisture sorption isotherm was then used to tie the threshold to the exposure relative humidity above which this occurs. Kinetic uptake studies were used to estimate the maximum safe exposure time at a given humidity (a square root time dependence of moisture uptake was observed). Armed with this knowledge, a FDGP compact coated with a compression coat [100% bees wax or combinations of carnauba wax (70%) with HPC (30%) or Avicel(®) PH 102 (30%) or lactose monohydrate (30%)] was developed that will insure the shelf life of the material without the need for special handling for approximately more than 3 months.

A First-Time-In-Human Phase I Clinical Trial of Bispecific Antibody-Targeted, Paclitaxel-Packaged Bacterial Minicells

PubMed Central

Rosenthal, Mark; McArthur, Grant A.; Pattison, Scott T.; Pattison, Stacey L.; MacDiarmid, Jennifer; Brahmbhatt, Himanshu; Scott, Andrew M.

2015-01-01

Background We have harnessed a novel biological system, the bacterial minicell, to deliver cancer therapeutics to cancer cells. Preclinical studies showed that epidermal growth factor receptor (EGFR)-targeted, paclitaxel-loaded minicells (EGFRminicellsPac) have antitumor effects in xenograft models. To examine the safety of the minicell delivery system, we initiated a first-time-in-human, open-label, phase I clinical study of EGFRminicellsPac in patients with advanced solid tumors. Methodology Patients received 5 weekly infusions followed by a treatment free week. Seven dose levels (1x108, 1x109, 3x109, 1x1010, 1.5x1010, 2x1010, 5x1010) were evaluated using a 3+3 dose-escalation design. Primary objectives were safety, tolerability and determination of the maximum tolerated dose. Secondary objectives were assessment of immune/inflammatory responses and antitumor activity. Principal Findings Twenty eight patients were enrolled, 22 patients completed at least one cycle of EGFRminicellsPac; 6 patients did not complete a cycle due to rapidly progressive disease. A total of 236 doses was delivered over 42 cycles, with a maximum of 45 doses administered to a single patient. Most common treatment-related adverse events were rigors and pyrexia. No deaths resulted from treatment-related adverse events and the maximum tolerated dose was defined as 1x1010 EGFRminicellsPac. Surprisingly, only a mild self-limiting elevation in the inflammatory cytokines IL-6, IL-8 and TNFα and anti-inflammatory IL-10 was observed. Anti-LPS antibody titers peaked by dose 3 and were maintained at that level despite repeat dosing with the bacterially derived minicells. Ten patients (45%; n = 22) achieved stable disease as their best response. Conclusions/Significance This is the first study in humans of a novel biological system that can provide targeted delivery of a range of chemotherapeutic drugs to solid tumor cells. Bispecific antibody-targeted minicells, packaged with the chemotherapeutic paclitaxel, were shown to be safe in patients with advanced solid tumors with modest clinical efficacy observed. Further study in Phase II trials is planned. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12609000672257 PMID:26659127

Directly ventricular septal defect closure without using arteriovenous wire loop: Our adult case series using transarterial retrograde approach

PubMed Central

Pekel, Nihat; Ercan, Ertuğrul; Özpelit, Mehmet Emre; Özyurtlu, Ferhat; Yılmaz, Akar; Topaloğlu, Caner; Saygı, Serkan; Yakan, Serkan; Tengiz, İstemihan

2017-01-01

Objective: The standard transcatheter ventricular septal defects (VSD) closure procedure is established with arteriovenous (AV) loop and is called as antegrade approach. The directly retrograde transarterial VSD closure without using AV loop might be better option as shortens the procedure time and decreases radiation exposure. Methods: Our series consist of twelve sequential adult cases with congenital VSDs (seven with perimembranous, four with muscular, one with postoperative residuel VSD). The mean age was 26.9 (Range 18–58), the mean height was 168.75 cm (Range 155–185cm), and the mean body mass index was 23.4 (Range 17.3–28.4). Maximum and minimum defect sizes were 10 and 5 mm and the mean defect size was 6.24 mm. The procedure was performed with left heart catheterization and advancing the delivery sheath over the stiff exchange wire then VSD occlusion from left side. Results: The defects were successfully closed with this technique in eleven patients. In sixth patient, the defect could not be cannulated by the delivery sheath, as the tip of the sheath did not reach the defect and VSD was closed with same sheath by standard transvenous approach using AV loop. We didn’t encounter any complication releated to semilunar or atrioventricular valves. Atrioventricular conduction system was not affected by the procedure in any patients. The median procedure and fluoroscopy times were 66 and 16.5 minutes respectively. Conclusion: Transarterial retrograde VSD closure without using AV loop simplifies the procedure, decreases the radiation exposure, and shortens the procedure time. The only limitation in adult patients is delivery sheath length. PMID:28315566

A time motion study in the immunization clinic of a tertiary care hospital of kolkata, west bengal.

PubMed

Chattopadhyay, Amitabha; Ghosh, Ritu; Maji, Sucharita; Ray, Tapobroto Guha; Lahiri, Saibendu Kumar

2012-01-01

A time and motion study is used to determine the amount of time required for a specific activity, work function, or mechanical process. Few such studies have been reported in the outpatient department of institutions, and such studies based exclusively on immunization clinic of an institute is a rarity. This was an observational cross sectional study done in the immunization clinic of R.G. Kar Medical College, Kolkata, over a period of 1 month (September 2010). The study population included mother/caregivers attending the immunization clinics with their children. The total sample was 482. Pre-synchronized stopwatches were used to record service delivery time at the different activity points. Median time was the same for both initial registration table and nutrition and health education table (120 seconds), but the vaccination and post vaccination advice table took the highest percentage of overall time (46.3%). Maximum time spent on the vaccination and post vaccination advice table was on Monday (538.1 s) and nutritional assessment and health assessment table took maximum time on Friday (217.1 s). Time taken in the first half of immunization session was more in most of the tables. The goal for achieving universal immunization against vaccine-preventable diseases requires multifaceted collated response from many stakeholders. Efficient functioning of immunization clinics is therefore required to achieve the prescribed goals. This study aims to initiate an effort to study the utilization of time at a certain health care unit with the invitation of much more in depth analysis in future.

Four-dimensional dose distributions of step-and-shoot IMRT delivered with real-time tumor tracking for patients with irregular breathing: Constant dose rate vs dose rate regulation

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

Yang Xiaocheng; Han-Oh, Sarah; Gui Minzhi

2012-09-15

Purpose: Dose-rate-regulated tracking (DRRT) is a tumor tracking strategy that programs the MLC to track the tumor under regular breathing and adapts to breathing irregularities during delivery using dose rate regulation. Constant-dose-rate tracking (CDRT) is a strategy that dynamically repositions the beam to account for intrafractional 3D target motion according to real-time information of target location obtained from an independent position monitoring system. The purpose of this study is to illustrate the differences in the effectiveness and delivery accuracy between these two tracking methods in the presence of breathing irregularities. Methods: Step-and-shoot IMRT plans optimized at a reference phase weremore » extended to remaining phases to generate 10-phased 4D-IMRT plans using segment aperture morphing (SAM) algorithm, where both tumor displacement and deformation were considered. A SAM-based 4D plan has been demonstrated to provide better plan quality than plans not considering target deformation. However, delivering such a plan requires preprogramming of the MLC aperture sequence. Deliveries of the 4D plans using DRRT and CDRT tracking approaches were simulated assuming the breathing period is either shorter or longer than the planning day, for 4 IMRT cases: two lung and two pancreatic cases with maximum GTV centroid motion greater than 1 cm were selected. In DRRT, dose rate was regulated to speed up or slow down delivery as needed such that each planned segment is delivered at the planned breathing phase. In CDRT, MLC is separately controlled to follow the tumor motion, but dose rate was kept constant. In addition to breathing period change, effect of breathing amplitude variation on target and critical tissue dose distribution is also evaluated. Results: Delivery of preprogrammed 4D plans by the CDRT method resulted in an average of 5% increase in target dose and noticeable increase in organs at risk (OAR) dose when patient breathing is either 10% faster or slower than the planning day. In contrast, DRRT method showed less than 1% reduction in target dose and no noticeable change in OAR dose under the same breathing period irregularities. When {+-}20% variation of target motion amplitude was present as breathing irregularity, the two delivery methods show compatible plan quality if the dose distribution of CDRT delivery is renormalized. Conclusions: Delivery of 4D-IMRT treatment plans, stemmed from 3D step-and-shoot IMRT and preprogrammed using SAM algorithm, is simulated for two dynamic MLC-based real-time tumor tracking strategies: with and without dose-rate regulation. Comparison of cumulative dose distribution indicates that the preprogrammed 4D plan is more accurately and efficiently conformed using the DRRT strategy, as it compensates the interplay between patient breathing irregularity and tracking delivery without compromising the segment-weight modulation.« less

48 CFR 16.501-1 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... maximum quantity) and that provides for the issuance of orders for the performance of tasks during the... of orders for the delivery of supplies during the period of the contract. Task-order contract means a...

Absence of lung fibrosis after a single pulmonary delivery of lipid nanocapsules in rats.

PubMed

Hureaux, José; Lacoeuille, Franck; Lagarce, Frédéric; Rousselet, Marie-Christine; Contini, Aurélien; Saulnier, Patrick; Benoit, Jean-Pierre; Urban, Thierry

2017-01-01

Lipid nanocapsules (LNCs) are potential drug carriers for pulmonary delivery since they can be nebulized without any structural or functional changes, and the aerosols produced are highly compatible with pulmonary drug delivery in human beings. The alveolar surface tension, in vitro cytotoxicity, biodistribution and pulmonary toxicity in rats of a single endotracheal spray of LNCs or paclitaxel-loaded LNCs were studied. In vitro cytotoxicity of LNCs after a spray remained unchanged. Biodistribution study showed a homogeneous repartition in the lungs in rats with an improvement in lung retention of the radiolabeled tracer loaded in LNCs compared to the absence of LNCs with a lung half-time of 8.8±0.7 hours. Bronchoalveolar fluid analysis revealed transient 7-day alveolar inflammation, reaching a maximum between days 2 and 4, characterized by a peak of granulocytes at day 1 followed by a peak of lymphocytes at day 3. Alveolar protein levels were increased at days 3 and 7. Acute inflammation was increased with paclitaxel-loaded LNCs in comparison with blank LNCs but dropped out at day 7. No histological pulmonary lesion was observed at day 60. LNCs lowered surface tension to a greater degree than Curosurf ® in a physicochemical model of the pulmonary alveolus. A single pulmonary delivery of LNCs induces a short-term alveolar inflammation with no residual lesions in rats at day 60. These data permit to start the study of LNCs in surfactant replacement therapy.

Linking log files with dosimetric accuracy--A multi-institutional study on quality assurance of volumetric modulated arc therapy.

PubMed

Pasler, Marlies; Kaas, Jochem; Perik, Thijs; Geuze, Job; Dreindl, Ralf; Künzler, Thomas; Wittkamper, Frits; Georg, Dietmar

2015-12-01

To systematically evaluate machine specific quality assurance (QA) for volumetric modulated arc therapy (VMAT) based on log files by applying a dynamic benchmark plan. A VMAT benchmark plan was created and tested on 18 Elekta linacs (13 MLCi or MLCi2, 5 Agility) at 4 different institutions. Linac log files were analyzed and a delivery robustness index was introduced. For dosimetric measurements an ionization chamber array was used. Relative dose deviations were assessed by mean gamma for each control point and compared to the log file evaluation. Fourteen linacs delivered the VMAT benchmark plan, while 4 linacs failed by consistently terminating the delivery. The mean leaf error (±1SD) was 0.3±0.2 mm for all linacs. Large MLC maximum errors up to 6.5 mm were observed at reversal positions. Delivery robustness index accounting for MLC position correction (0.8-1.0) correlated with delivery time (80-128 s) and depended on dose rate performance. Dosimetric evaluation indicated in general accurate plan reproducibility with γ(mean)(±1 SD)=0.4±0.2 for 1 mm/1%. However single control point analysis revealed larger deviations and attributed well to log file analysis. The designed benchmark plan helped identify linac related malfunctions in dynamic mode for VMAT. Log files serve as an important additional QA measure to understand and visualize dynamic linac parameters. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Operation DOMINIC, SHOT SWORD FISH. Scientific Director’s Summary Report

DTIC Science & Technology

1985-09-01

charges, undoubtedly reflects a design decision that balanced thp tactical need for flexibility in using the weapon against the desire to ensure...further if the commanding officer is to take maximum advantage of his increased weapon delivery flexibility . i.2 SIGNIFICANCE OF SWORD FISH AS AN...turn, is governed by the pulsation and upward z.gration of the steam bubble formed in the water after the burst. The base surge, at ranges of delivery

Design and in vivo evaluation of a patch delivery system for insulin based on thiolated polymers.

PubMed

Grabovac, Vjera; Föger, Florian; Bernkop-Schnürch, Andreas

2008-02-04

The aim of this study was to develop and evaluate a novel three-layered oral delivery system for insulin in vivo. The patch system consisted of a mucoadhesive layer, a water insoluble backing layer made of ethylcellulose and an enteric coating made of Eudragit. Drug release studies were performed in media mimicking stomach and intestinal fluids. For in vivo studies patch systems were administered orally to conscious non-diabetic rats. Orally administered insulin in aqueous solution was used as control. After the oral administration of the patch systems a decrease of glucose and increase of insulin blood levels were measured. The mucoadhesive layer, exhibiting a diameter of 2.5mm and a weight of 5mg, comprised polycarbophil-cysteine conjugate (49%), bovine insulin (26%), gluthatione (5%) and mannitol (20%). 74.8+/-4.8% of insulin was released from the delivery system over 6h. Six hours after administration of the patch system mean maximum decrease of blood glucose level of 31.6% of the initial value could be observed. Maximum insulin concentration in blood was 11.3+/-6.2ng/ml and was reached 6h after administration. The relative bioavailability of orally administered patch system versus subcutaneous injection was 2.2%. The results indicate that the patch system provides enhancement of intestinal absorption and thereby offers a promising strategy for peroral peptide delivery.

Mucoadhesive films containing chitosan-coated nanoparticles: a new strategy for buccal curcumin release.

PubMed

Mazzarino, Letícia; Borsali, Redouane; Lemos-Senna, Elenara

2014-11-01

Mucoadhesive films containing curcumin-loaded nanoparticles were developed, aiming to prolong the residence time of the dosage form in the oral cavity and to increase drug absorption through the buccal mucosa. Films were prepared by the casting method after incorporation of curcumin-loaded chitosan-coated polycaprolactone nanoparticles into plasticized chitosan solutions. Different molar masses of mucoadhesive polysaccharide chitosan and concentrations of plasticizer glycerol were used to optimize the preparation conditions. Films obtained using medium and high molar mass chitosan were found to be homogeneous and flexible. Curcumin-loaded nanoparticles were uniformly distributed on the film surface, as evidenced by atomic force microscopy and high-resolution field-emission gun scanning electron microscopy (FEG-SEM) images. Analyses of film cross sections using FEG-SEM demonstrate the presence of nanoparticles inside the films. In addition, films proved to have a good rate of hydration in simulated saliva solution, displaying a maximum swelling of around 80% and in vitro prolonged-controlled delivery of curcumin. These results indicate that the mucoadhesive films containing nanoparticles offer a promising approach for buccal delivery of curcumin, which may be particularly useful in the treatment of periodontal diseases that require a sustained drug delivery. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

SU-E-T-144: Effective Analysis of VMAT QA Generated Trajectory Log Files for Medical Accelerator Predictive Maintenance

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

Able, CM; Baydush, AH; Nguyen, C

Purpose: To determine the effectiveness of SPC analysis for a model predictive maintenance process that uses accelerator generated parameter and performance data contained in trajectory log files. Methods: Each trajectory file is decoded and a total of 131 axes positions are recorded (collimator jaw position, gantry angle, each MLC, etc.). This raw data is processed and either axis positions are extracted at critical points during the delivery or positional change over time is used to determine axis velocity. The focus of our analysis is the accuracy, reproducibility and fidelity of each axis. A reference positional trace of the gantry andmore » each MLC is used as a motion baseline for cross correlation (CC) analysis. A total of 494 parameters (482 MLC related) were analyzed using Individual and Moving Range (I/MR) charts. The chart limits were calculated using a hybrid technique that included the use of the standard 3σ limits and parameter/system specifications. Synthetic errors/changes were introduced to determine the initial effectiveness of I/MR charts in detecting relevant changes in operating parameters. The magnitude of the synthetic errors/changes was based on: TG-142 and published analysis of VMAT delivery accuracy. Results: All errors introduced were detected. Synthetic positional errors of 2mm for collimator jaw and MLC carriage exceeded the chart limits. Gantry speed and each MLC speed are analyzed at two different points in the delivery. Simulated Gantry speed error (0.2 deg/sec) and MLC speed error (0.1 cm/sec) exceeded the speed chart limits. Gantry position error of 0.2 deg was detected by the CC maximum value charts. The MLC position error of 0.1 cm was detected by the CC maximum value location charts for every MLC. Conclusion: SPC I/MR evaluation of trajectory log file parameters may be effective in providing an early warning of performance degradation or component failure for medical accelerator systems.« less

[Comparison of TTR and CMV promoters in vivo and in vitro via a secreted luciferase reporter system].

PubMed

Luo, Shun-Tao; Tian, Wen-Hong; Wang, Gang; Dong, Xiao-Yan; Yang, Li; Wu, Xiao-Bing

2009-11-01

GLuc (Gaussia luciferase) is a secreted luciferase with high sensitivity. In this study, we primarily compared expression character of PTTR with that of PCMV, relied on easy secretion, high sensitivity and simple and fast detection of GLuc. We firstly constructed two plasmids pAAV2-neo-TTR-GLuc and pAAV2-neo-CMV-GLuc. Then, 4 cell lines were transfected with the two plasmids in aid of Lipofectamine 2000, including Huh7 and HepG2, which are derived from liver cells, as well as HEK293 and HeLaS3 cells, which are non-liver cell lines. We monitored the expression of GLuc in the supernatant of these cell cultures at different time points post-transfection. Furthermore, we injected the two plasmids with different doses into BALB/c mice by the means of hydrodynamic delivery and monitored the GLuc expression in vivo with 2.5 microl tail tip blood since 2 h post-injection. The cell assay results suggested that the expression of GLuc driven by CMV promoter was significantly higher than that of GLuc driven by TTR promoter. And, the luciferase activity of GLuc driven by CMV promoter was 50-300 times higher than that of GLuc driven by TTR promoter in HEK293 and HeLaS3 cell lines, but less than 10 times higher than that of GLuc driven by TTR promoter in the HepG2 and Huh7 cell lines, indicating the relative liver-specificity of TTR promoter. In the animal assay, the higher luciferase activity was determined in CMV promoter group than in TTR promoter group at different doses of the two plasmids. But the expression patterns for the two promoters differed obviously. The expression of GLuc driven by CMV promoter reached the maximum 10 hours post-injection and declined rapidly; while the expression of GLuc driven by TTR promoter reached the maximum 48 hours after delivery, and declined very slowly. These results implied that PTTR could keep expression of driven gene in a long time although its expression intensity is lower than PCMV's. Thus, it is more suitable for maintaining longer expression of target genes in liver.

Experimental study of air delivery into water-conveyance system of the radial-axial turbine

NASA Astrophysics Data System (ADS)

Maslennikova, Alexandra; Platonov, Dmitry; Minakov, Andrey; Dekterev, Dmitry

2017-10-01

The paper presents an experimental study of oscillatory response in the Francis turbine of hydraulic unit. The experiment was performed on large-scale hydrodynamic test-bench with impeller diameter of 0.3 m. The effect of air injection on the intensity of pressure pulsations was studied at the maximum pressure pulsations in the hydraulic unit. It was revealed that air delivery into the water-conveyance system of the turbine results in almost two-fold reduction of pressure pulsations.

An automatic pellet dispenser for precise control of feeding topography in granivorous birds

PubMed Central

Berkhoudt, H.; Van Der Reijden, D.; Heijmans, M.

1987-01-01

Design and construction of an automatic pellet dispenser for granivorous birds are described. The dispenser permits rapid pneumatic delivery of pellets (five pellets per second maximum) to one controlled position and does not interfere with simultaneous electrophysiological recording. In addition, the device continuously indicates presence or absence of a pellet in the delivery position. This automatic dispenser proved very effective in our studies of stereotyped topographies of feeding in granivorous birds, such as pigeons and chickens. PMID:16812503

TU-CD-304-03: Dosimetric Verification and Preliminary Comparison of Dynamic Wave Arc for SBRT Treatments

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

Burghelea, M; BRAINLAB AG, Munich; Babes Bolyai University, Cluj-Napoca

2015-06-15

Purpose: To evaluate the potential dosimetric benefits and verify the delivery accuracy of Dynamic Wave Arc, a novel treatment delivery approach for the Vero SBRT system. Methods: Dynamic Wave Arc (DWA) combines simultaneous movement of gantry/ring with inverse planning optimization, resulting in an uninterrupted non-coplanar arc delivery technique. Thirteen SBRT complex cases previously treated with 8–10 conformal static beams (CRT) were evaluated in this study. Eight primary centrally-located NSCLC (prescription dose 4×12Gy or 8×7.5Gy) and five oligometastatic cases (2×2 lesions, 10×5Gy) were selected. DWA and coplanar VMAT plans, partially with dual arcs, were generated for each patient using identical objectivemore » functions for target volumes and OARs on the same TPS (RayStation, RaySearch Laboratories). Dosimetric differences and delivery time among these three planning schemes were evaluated. The DWA delivery accuracy was assessed using the Delta4 diode array phantom (ScandiDos AB). The gamma analysis was performed with the 3%/3mm dose and distance-to-agreement criteria. Results: The target conformity for CRT, VMAT and DWA were 0.95±0.07, 0.96±0.04 and 0.97±0.04, while the low dose spillage gradient were 5.52±1.36, 5.44±1.11, and 5.09±0.98 respectively. Overall, the bronchus, esophagus and spinal cord maximum doses were similar between VMAT and DWA, but highly reduced compared with CRT. For the lung cases, the mean dose and V20Gy were lower for the arc techniques compares with CRT, while for the liver cases, the mean dose and the V30Gy presented slightly higher values. The average delivery time of VMAT and DWA were 2.46±1.10 min and 4.25±1.67 min, VMAT presenting shorter treatment time in all cases. The DWA dosimetric verification presented an average gamma index passing rate of 95.73±1.54% (range 94.2%–99.8%). Conclusion: Our preliminary data indicated that the DWA is deliverable with clinically acceptable accuracy and has the potential to further improve the plan quality. This collaborative work was supported by the Flemish government through the Hercules foundation and corporate funding from BrainLab AG. The first and the sixth author are financially supported by Brainlab AG. The other authors have no conflict of interest.« less

Online 3D EPID-based dose verification: Proof of concept.

PubMed

Spreeuw, Hanno; Rozendaal, Roel; Olaciregui-Ruiz, Igor; González, Patrick; Mans, Anton; Mijnheer, Ben; van Herk, Marcel

2016-07-01

Delivery errors during radiotherapy may lead to medical harm and reduced life expectancy for patients. Such serious incidents can be avoided by performing dose verification online, i.e., while the patient is being irradiated, creating the possibility of halting the linac in case of a large overdosage or underdosage. The offline EPID-based 3D in vivo dosimetry system clinically employed at our institute is in principle suited for online treatment verification, provided the system is able to complete 3D dose reconstruction and verification within 420 ms, the present acquisition time of a single EPID frame. It is the aim of this study to show that our EPID-based dosimetry system can be made fast enough to achieve online 3D in vivo dose verification. The current dose verification system was sped up in two ways. First, a new software package was developed to perform all computations that are not dependent on portal image acquisition separately, thus removing the need for doing these calculations in real time. Second, the 3D dose reconstruction algorithm was sped up via a new, multithreaded implementation. Dose verification was implemented by comparing planned with reconstructed 3D dose distributions delivered to two regions in a patient: the target volume and the nontarget volume receiving at least 10 cGy. In both volumes, the mean dose is compared, while in the nontarget volume, the near-maximum dose (D2) is compared as well. The real-time dosimetry system was tested by irradiating an anthropomorphic phantom with three VMAT plans: a 6 MV head-and-neck treatment plan, a 10 MV rectum treatment plan, and a 10 MV prostate treatment plan. In all plans, two types of serious delivery errors were introduced. The functionality of automatically halting the linac was also implemented and tested. The precomputation time per treatment was ∼180 s/treatment arc, depending on gantry angle resolution. The complete processing of a single portal frame, including dose verification, took 266 ± 11 ms on a dual octocore Intel Xeon E5-2630 CPU running at 2.40 GHz. The introduced delivery errors were detected after 5-10 s irradiation time. A prototype online 3D dose verification tool using portal imaging has been developed and successfully tested for two different kinds of gross delivery errors. Thus, online 3D dose verification has been technologically achieved.

How do Watershed Characteristics and Precipitation Influence Post-Wildfire Valley Sediment Storage and Delivery Over Time?

NASA Astrophysics Data System (ADS)

Brogan, D. J.; Nelson, P. A.; MacDonald, L. H.

2016-12-01

Considerable advances have been made in understanding post-wildfire runoff, erosion, and mass wasting at the hillslope and small watershed scale, but the larger-scale effects on flooding, water quality, and sedimentation are often the most significant impacts. The problem is that we have virtually no watershed-specific tools to quantify the proportion of eroded sediment that is stored or delivered from watersheds larger than about 2-5 km2. In this study we are quantifying how channel and valley bottom characteristics affect post-wildfire sediment storage and delivery. Our research is based on intensive monitoring of sediment storage over time in two 15 km2 watersheds (Skin Gulch and Hill Gulch) burned in the 2012 High Park Fire using repeated cross section and longitudinal surveys from fall 2012 through summer 2016, five airborne laser scanning (ALS) datasets from fall 2012 through summer 2015, and both radar and ground-based precipitation measurements. We have computed changes in sediment storage by differencing successive cross sections, and computed spatially explicit changes in successive ALS point clouds using the multiscale model to model cloud comparison (M3C2) algorithm. These channel changes are being related to potential morphometric controls, including valley width, valley slope, confinement, contributing area, valley expansion or contraction, topographic curvature (planform and profile), and estimated sediment inputs. We hypothesize that maximum rainfall intensity and lateral confinement will be the primary independent variables that describe observed patterns of erosion and deposition, and that the results can help predict post-wildfire sediment delivery and identify high priority areas for restoration.

Volumetric Modulated Arc Radiotherapy for Vestibular Schwannomas

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

Lagerwaard, Frank J.; Meijer, Otto W.M.; Hoorn, Elles A.P. van der

2009-06-01

Purpose: To evaluate volumetric modulated arc radiotherapy (RapidArc [RA]), a novel approach allowing for rapid treatment delivery, for the treatment of vestibular schwannoma (VS). Methods and Materials: The RA plans were generated for a small (0.5 cm{sup 3}), intermediate (2.8 cm{sup 3}), and large (14.8 cm{sup 3}) VS. The prescription dose was 12.5 Gy to the encompassing 80% isodose. The RA plans were compared with conventional radiosurgery plans using both a single dynamic conformal arc (1DCA) and five noncoplanar dynamic conformal arcs (5DCA). Conformity indices (CI) and dose-volume histograms of critical organs were compared. The RA plan for the medium-sizedmore » VS was measured in a phantom using Gafchromic EBT films and compared with calculated dose distributions. Results: The RA planning was completed within 30 min in all cases, and calculated treatment delivery time (after patient setup) was 5 min vs. 20 min for 5DCA. A superior CI was achieved with RA, with a substantial decrease in low-dose irradiation of the normal brain achieved relative to 5DCA plans. Maximum doses to critical organs were similar for RA and 5DCA but were higher for 1DCA. Film measurements showed the differences between calculated and measured doses to be smaller than 1.5% in the high-dose area and smaller than 3% in the low-dose area. Conclusion: The RA plans consistently achieved a higher CI and decrease in areas of low-dose irradiation. This, together with shorter treatment delivery times, has led to RA replacing our conventional five-arc radiosurgery technique for VS.« less

Revisiting the daily human birth pattern: time of delivery at Casa de Maternidad in Madrid (1887-1892).

PubMed

Varea, Carlos; Fernández-Cerezo, Susana

2014-01-01

Among the ancestral characteristics of the primate group to which Homo sapiens belongs we find a pattern of daytime physical activity, but one notable exception is birthing which usually begins with night-time labor. In populations with a moderate or high level of medicalized labor, there is evidence that the medical preferences interfere with the underlying biological mechanism for the circadian pattern of human birth. This study analyses the hourly patterns of 4,599 single live births in the House of Maternity in Madrid between 1887 and 1892, a period of very limited obstetric intervention and without the influence of artificial lighting. In order to determine the influence of natural light on labor, two periods of maximum and minimum light have been established around the summer and winter solstices of the years in question. A clear circadian pattern of births emerges, with very early morning and early morning births dominating, and a sharp drop from midday until nightfall. The hourly distribution on both solstices follows this pattern, but with a clear peak shift: in winter, there is a greater concentration of deliveries in the early morning, whereas in the summer, the highest concentration is between 8 and 12 in the morning. The results confirm that non-intervened human birth has a clear diurnal cycle, with a higher incidence of deliveries in the early morning or morning. The shift in distribution during the winter and summer solstices seems to confirm the effect of light on the labor process. © 2014 Wiley Periodicals, Inc.

Contrasting Patterns of Fine Fluvial Sediment Delivery in Two Adjacent Upland Catchments

NASA Astrophysics Data System (ADS)

Perks, M.; Bracken, L.; Warburton, J.

2010-12-01

Quantifying patterns of fine suspended sediment transfer in UK upland rivers is of vital importance in combating the damaging effects of elevated fluxes of suspended sediment, and sediment associated transport of contaminants, on in-stream biota. In many catchments of the UK there is still a lack of catchment-wide understanding of both the spatial patterns and temporal variation in fine sediment delivery. This poster describes the spatial and temporal distribution of in-stream fine sediment delivery from a network of 44 time-integrated mass flux samplers (TIMs) in two adjacent upland catchments. The two catchments are the Esk (210 km2) and Upper Derwent (236 km2) which drain the North York Moors National Park. Annual suspended sediment loads in the Upper Derwent are 1273 t, whereas in the Esk catchment they are greater at 1778 t. Maximum yields of 22 t km-2 yr -1 were measured in the headwater tributaries of the Rye River (Derwent), whereas peak yields in the Esk are four times greater (98 t km-2 yr-1) on the Butter Beck subcatchment. Analysis of the within-storm sediment dynamics, indicates that the sediment sources within the Upper Derwent catchment are from distal locations possibly mobilised by hillslope runoff processes, whereas in the Esk, sediment sources are more proximal to the channel e.g. within channel stores or bank failures. These estimates of suspended sediment flux are compared with the diffuse pollution potential generated by a risk-based model of sediment transfer (SCIMAP) in order to assess the similarity between the model predictions and observed fluxes.

Preparation and controlled release of mesoporous MCM-41/propranolol hydrochloride composite drug.

PubMed

Zhai, Qing-Zhou

2013-01-01

This article used MCM-41 as a carrier for the assembly of propranolol hydrochloride by the impregnation method. By means of chemical analysis, powder X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) spectroscopy and low-temperature N(2) adsorption-desorption at 77 K, the characterization was made for the prepared materials. The propranolol hydrochloride guest assembly capacity was 316.20 ± 0.31 mg/g (drug/MCM-41). Powder XRD test results indicated that during the process of incorporation, the frameworks of the MCM-41 were not destroyed and the crystalline degrees of the host-guest nanocomposite materials prepared still remained highly ordered. Characterization by SEM and TEM showed that the composite material presented spherical particle and the average particle size of composite material was 186 nm. FT-IR spectra showed that the MCM-41 framework existed well in the (MCM-41)-propranolol hydrochloride composite. Low-temperature nitrogen adsorption-desorption results at 77 K showed that the guest partially occupied the channels of the molecular sieves. Results of the release of the prepared composite drug in simulated body fluid indicated that the drug can release up to 32 h and its maximum released amount was 99.20 ± 0.11%. In the simulated gastric juice release pattern of drug, the maximum time for the drug release was discovered to be 6 h and the maximum cumulative released amount of propranolol hydrochloride was 45.13 ± 0.23%. The drug sustained-release time was 10 h in simulated intestinal fluid and the maximum cumulative released amount was 62.05 ± 0.13%. The prepared MCM-41 is a well-controlled drug delivery carrier.

Maximum Data Collection Rate Routing Protocol Based on Topology Control for Rechargeable Wireless Sensor Networks

PubMed Central

Lin, Haifeng; Bai, Di; Gao, Demin; Liu, Yunfei

2016-01-01

In Rechargeable Wireless Sensor Networks (R-WSNs), in order to achieve the maximum data collection rate it is critical that sensors operate in very low duty cycles because of the sporadic availability of energy. A sensor has to stay in a dormant state in most of the time in order to recharge the battery and use the energy prudently. In addition, a sensor cannot always conserve energy if a network is able to harvest excessive energy from the environment due to its limited storage capacity. Therefore, energy exploitation and energy saving have to be traded off depending on distinct application scenarios. Since higher data collection rate or maximum data collection rate is the ultimate objective for sensor deployment, surplus energy of a node can be utilized for strengthening packet delivery efficiency and improving the data generating rate in R-WSNs. In this work, we propose an algorithm based on data aggregation to compute an upper data generation rate by maximizing it as an optimization problem for a network, which is formulated as a linear programming problem. Subsequently, a dual problem by introducing Lagrange multipliers is constructed, and subgradient algorithms are used to solve it in a distributed manner. At the same time, a topology controlling scheme is adopted for improving the network’s performance. Through extensive simulation and experiments, we demonstrate that our algorithm is efficient at maximizing the data collection rate in rechargeable wireless sensor networks. PMID:27483282

Maximum Data Collection Rate Routing Protocol Based on Topology Control for Rechargeable Wireless Sensor Networks.

PubMed

Lin, Haifeng; Bai, Di; Gao, Demin; Liu, Yunfei

2016-07-30

In Rechargeable Wireless Sensor Networks (R-WSNs), in order to achieve the maximum data collection rate it is critical that sensors operate in very low duty cycles because of the sporadic availability of energy. A sensor has to stay in a dormant state in most of the time in order to recharge the battery and use the energy prudently. In addition, a sensor cannot always conserve energy if a network is able to harvest excessive energy from the environment due to its limited storage capacity. Therefore, energy exploitation and energy saving have to be traded off depending on distinct application scenarios. Since higher data collection rate or maximum data collection rate is the ultimate objective for sensor deployment, surplus energy of a node can be utilized for strengthening packet delivery efficiency and improving the data generating rate in R-WSNs. In this work, we propose an algorithm based on data aggregation to compute an upper data generation rate by maximizing it as an optimization problem for a network, which is formulated as a linear programming problem. Subsequently, a dual problem by introducing Lagrange multipliers is constructed, and subgradient algorithms are used to solve it in a distributed manner. At the same time, a topology controlling scheme is adopted for improving the network's performance. Through extensive simulation and experiments, we demonstrate that our algorithm is efficient at maximizing the data collection rate in rechargeable wireless sensor networks.

Transit time affects the community stability of Lactobacillus and Bifidobacterium species in an in vitro model of human colonic microbiotia.

PubMed

Rodes, Laetitia; Paul, Arghya; Coussa-Charley, Michael; Al-Salami, Hani; Tomaro-Duchesneau, Catherine; Fakhoury, Marc; Prakash, Satya

2011-12-01

Retention time, which is analogous to transit time, is an index for bacterial stability in the intestine. Its consideration is of particular importance to optimize the delivery of probiotic bacteria in order to improve treatment efficacy. This study aims to investigate the effect of retention time on Lactobacilli and Bifidobacteria stability using an established in vitro human colon model. Three retention times were used: 72, 96, and 144 h. The effect of retention time on cell viability of different bacterial populations was analyzed with bacterial plate counts and PCR. The proportions of intestinal Bifidobacteria, Lactobacilli, Enterococci, Staphylococci and Clostridia populations, analyzed by plate counts, were found to be the same as that in human colonic microbiota. Retention time in the human colon affected the stability of Lactobacilli and Bifidobacteria communities, with maximum stability observed at 144 h. Therefore, retention time is an important parameter that influences bacterial stability in the colonic microbiota. Future clinical studies on probiotic bacteria formulations should take into consideration gastrointestinal transit parameters to improve treatment efficacy.

Formulation of unidirectional release buccal patches of carbamazepine and study of permeation through porcine buccal mucosa

PubMed Central

Govindasamy, Parthasarathy; Kesavan, Bhaskar Reddy; Narasimha, Jayaveera Korlakunta

2013-01-01

Objective To achieve transbuccal release of carbamazepine by loading in unidirectional release mucoadhesive buccal patches. Methods Buccal patches of carbamazepine with unidirectional drug release were prepared using hydroxypropyl methyl cellulose, polyvinyl alcohol, polyvinyl pyrrolidone and ethyl cellulose by solvent casting method. Water impermeable backing layer (Pidilite® Biaxially-oriented polypropylene film) of patches provided unidirectional drug release. They were evaluated for thickness, mass uniformity, surface pH and folding endurance. Six formulations FA2, FA8, FA10, FB1, FB14 and FB16 (folding endurance above 250) were evaluated further for swelling studies, ex vivo mucoadhesive strength, ex vivo mucoadhesion time, in vitro drug release, ex vivo permeation, accelerated stability studies and FTIR and XRD spectral studies. Results The ex vivo mucoadhesion time of patches ranged between 109 min (FA10) to 126 min (FB14). The ex vivo mucoadhesive force was in the range of 0.278 to 0.479 kg/m/s. The in vitro drug release studies revealed that formulation FA8 released 84% and FB16 released 99.01% of drug in 140 min. Conclusions The prepared unidirectional buccal patches of carbamazepine provided a maximum drug release within specified mucoadhesion period and it indicates a potential alternative drug delivery system for systemic delivery of carbamazepine. PMID:24093793

Determination of a cutoff value for pelvic floor distensibility using the Epi-no balloon to predict perineal integrity in vaginal delivery: ROC curve analysis. Prospective observational single cohort study.

PubMed

Zanetti, Miriam Raquel Diniz; Petricelli, Carla Dellabarba; Alexandre, Sandra Maria; Paschoal, Aline; Araujo Júnior, Edward; Nakamura, Mary Uchiyama

2016-04-01

Several risk factors are involved in perineal lacerations during vaginal delivery. However, little is known about the influence of perineal distensibility as a protective factor. The aim here was to determine a cutoff value for pelvic floor distensibility measured using the Epi-no balloon, which could be used as a predictive factor for perineal integrity in vaginal delivery. Prospective observational single cohort study conducted in a maternity hospital. A convenience sample of 227 consecutive at-term parturients was used. All women had a single fetus in the vertex presentation, with up to 9.0 cm of dilation. The maximum dilation of the Epi-no balloon was measured using a tape measure after it had been inflated inside the vagina up to the parturients' maximum tolerance. The receiver operating characteristic (ROC) curve was used to obtain the Epi-no circumference measurement with best sensitivity and specificity. Among the 161 patients who were included in the study, 50.9% underwent episiotomy, 21.8% presented lacerations and 27.3% retained an intact perineum. Age > 25.9 years; number of pregnancies > 3.4; number of deliveries > 2.2 and circumference measured by Epi-no > 21.4 cm were all directly correlated with an intact perineum. Circumference measurements using the Epi-no balloon that were greater than 20.8 cm showed sensitivity and specificity of 70.5% and 66.7% (area under curve = 0.713), respectively, as a predictive factor for an intact perineum in vaginal delivery. Circumferences greater than 20.8 cm achieved using the Epi-no balloon are a predictive factor for perineal integrity in parturients.

[Is it already time to legalize the usage of Cytotec (Misoprostol) in the obstetrics' practice?].

PubMed

Bozhinova, S

2007-01-01

Cytotec (Misoprostol) is a prostaglandin E1 9(PgE1) analogue. Despite that it is not officially registered for obstetric and gynaecological targets, Cytotec (C) is widely used in this sphere. The author aims to study the effect and results from C application used for delivery (birth) induction, as well as means for cervical maturation. In order to reach this aim, beside the group of 45 pregnant women to who we applied C, we also reviewed the existing literature, which reported proves for C efficacy, pharma-kynetics and the safe aspects of its application (usage) in pregnancy. C was used with 45 pregnant women, divided in two groups: I group--27 pregnant women with oral application and II group--18 pregnant women with vaginal application. C was given per os in dosage 50 microg at 4 hours, the maximum dosage being 200 microg. When applied in the vagina, the dosage was twice 50 microg, every 6 hours. Four hours after the second dosage, if the effective delivery activity was not sufficient, we continued with sub-lingual application in dosage 50 microg every 4 hours till the regular delivery activity was reached. The vaginal delivery (childbirth) till the 24th hour of C application is considered as a successful induction. The delivery (childbirth) continuation, though with insignificant difference, is less under vaginal application. Uterine contractions begin (start) 30-35 minutes earlier under C application. Sectio Caesarea has smaller frequency under C application, in comparison with the general population frequency for the same period (year 2006 and the first half of 2007). The C induction is successful in 40 (88.89%), and with 7 (25.93%) the per oral application was prolonged via oxytocine infusion, and with half of the patients the vaginal application was continued via sun-lingual one. The author reaches the conclusion, that Cytotec is an effective and safe means for delivery (childbirth) induction, and that when dosage and application manner are set-up, the individual characterics of the patients should be taken into account. Mother-fetal results are the best under single dosage of 50 microg, applied in per oral, vaginal or sub-lingual way. Due to the wide application of Cytotec medicine, it is already high time to legalize it and to standardize the protocols from its application.

Shoulder dystocia documentation: an evaluation of a documentation training intervention.

PubMed

LeRiche, Tammy; Oppenheimer, Lawrence; Caughey, Sharon; Fell, Deshayne; Walker, Mark

2015-03-01

To evaluate the quality and content of nurse and physician shoulder dystocia delivery documentation before and after MORE training in shoulder dystocia management skills and documentation. Approximately 384 charts at the Ottawa Hospital General Campus involving a diagnosis of shoulder dystocia between the years of 2000 and 2006 excluding the training year of 2003 were identified. The charts were evaluated for 14 key components derived from a validated instrument. The delivery notes were then scored based on these components by 2 separate investigators who were blinded to delivery note author, date, and patient identification to further quantify delivery record quality. Approximately 346 charts were reviewed for physician and nurse delivery documentation. The average score for physician notes was 6 (maximum possible score of 14) both before and after the training intervention. The nurses' average score was 5 before and after the training intervention. Negligible improvement was observed in the content and quality of shoulder dystocia documentation before and after nurse and physician training.

Dosimetric Comparison between Single and Dual Arc-Volumetric Modulated Arc Radiotherapy and Intensity Modulated Radiotherapy for Nasopharyngeal Carcinoma Using a Simultaneous Integrated Boost Technique

PubMed Central

Radhakrishnan, Sivakumar; Chandrasekaran, Anuradha; Sarma, Yugandhar; Balakrishnan, Saranganathan; Nandigam, Janardhan

2017-01-01

Backround: Plan quality and performance of dual arc (DA) volumetric modulated arc therapy (VMAT), single arc (SA) VMAT and nine field (9F) intensity modulated radiotherapy were compared using a simultaneous integrated boost (SIB) technique. Methods: Twelve patients treated in Elekta Synergy Platform (mlci2) by 9F-IMRT were replanned with SA/DA-VMAT using a CMS Monaco Treatment Planning System (TPS) with Monte Carlo simulation. Target delineation was conducted as per Radiation Therapy Oncology Protocols (RTOG0225 and 0615). A 70Gy dose prescribed to PTV70 and 61Gy to PTV61 in 33 fractions was applied for the SIB technique. The conformity index (CI) and homogeneity index (HI) for targets and the mean dose and maximum dose for OAR’s, treatment delivery time (min), monitor units (MUs) per fraction, normal tissue integral dose and patient specific quality assurance were analysed. Results: Acceptable target coverage was achieved for PTV70 and PTV61 with all the planning techniques. No significant differences were observed except for D98 (PTV61), CI(PTV70) and HI(PTV61). Maximum dose (Dmax) to the spinal cord was lower in DA-VMAT than 9F-IMRT (p=0.002) and SA-VMAT (p=0.001). D50 (%) of parotid glands was better controlled by 9F-IMRT (p=0.001) and DA-VMAT (p=0.001) than SA-VMAT. A lower mean dose to the larynx was achieved with 9F-IMRT (P=0.001) and DA-VMAT (p=0.001) than with SA-VMAT. DA-VMAT achieved higher CI of PTV70 (P= 0.005) than SA-VMAT. For PTV61, DA-VMAT (P=0.001) and 9F-IMRT (P=0.001) achieved better HI than SA-VMAT. The average treatment delivery times were 7.67mins, 3.35 mins, 4.65 mins for 9F-IMRT, SA-VMAT and DA-VMAT, respectively. No significant difference were observed in MU/fr (p=0.9) and NTID (P=0.90) and the patient quality assurance pass rates were >95% (gamma analysis I3mm, 3%). Conclusion: DA-VMAT showed better conformity over target dose and spared the OARs better or equal to IMRT. SA-VMAT could not spare the OARs well. DA-VMAT offered shorter delivery time than IMRT without compromising the plan quality. PMID:28612593

Dosimetric Comparison between Single and Dual Arc-Volumetric Modulated Arc Radiotherapy and Intensity Modulated Radiotherapy for Nasopharyngeal Carcinoma Using a Simultaneous Integrated Boost Technique

PubMed

Radhakrishnan, Sivakumar; Chandrasekaran, Anuradha; Sarma, Yugandhar; Balakrishnan, Saranganathan; Nandigam, Janardhan

2017-05-01

Backround: Plan quality and performance of dual arc (DA) volumetric modulated arc therapy (VMAT) , single arc (SA) VMAT and nine field (9F) intensity modulated radiotherapy were compared using a simultaneous integrated boost (SIB) technique. Methods: Twelve patients treated in Elekta Synergy Platform (mlci2) by 9F-IMRT were replanned with SA/DA-VMAT using a CMS Monaco Treatment Planning System (TPS) with Monte Carlo simulation. Target delineation was conducted as per Radiation Therapy Oncology Protocols (RTOG0225 and 0615). A 70Gy dose prescribed to PTV70 and 61Gy to PTV61 in 33 fractions was applied for the SIB technique. The conformity index (CI) and homogeneity index (HI) for targets and the mean dose and maximum dose for OAR’s, treatment delivery time (min), monitor units (MUs) per fraction, normal tissue integral dose and patient specific quality assurance were analysed. Results: Acceptable target coverage was achieved for PTV70 and PTV61 with all the planning techniques. No significant differences were observed except for D98 (PTV61), CI(PTV70) and HI(PTV61). Maximum dose (Dmax) to the spinal cord was lower in DA-VMAT than 9F-IMRT (p=0.002) and SA-VMAT (p=0.001). D50 (%) of parotid glands was better controlled by 9F-IMRT (p=0.001) and DA-VMAT (p=0.001) than SA-VMAT. A lower mean dose to the larynx was achieved with 9F-IMRT (P=0.001) and DA-VMAT (p=0.001) than with SA-VMAT. DA-VMAT achieved higher CI of PTV70 (P= 0.005) than SA-VMAT. For PTV61, DA-VMAT (P=0.001) and 9F-IMRT (P=0.001) achieved better HI than SA-VMAT. The average treatment delivery times were 7.67mins, 3.35 mins, 4.65 mins for 9F- IMRT, SA-VMAT and DA-VMAT, respectively. No significant difference were observed in MU/fr (p=0.9) and NTID (P=0.90) and the patient quality assurance pass rates were >95% (gamma analysis Ґ3mm, 3%). Conclusion: DA-VMAT showed better conformity over target dose and spared the OARs better or equal to IMRT. SA-VMAT could not spare the OARs well. DA-VMAT offered shorter delivery time than IMRT without compromising the plan quality. Creative Commons Attribution License

Experimental validation of a deforming grid 4D dose calculation for PBS proton therapy.

PubMed

Krieger, Miriam; Klimpki, Grischa; Fattori, Giovanni; Hrbacek, Jan; Oxley, David; Safai, Sairos; Weber, Damien C; Lomax, Antony J; Zhang, Ye

2018-03-01

The aim of this study was to verify the temporal accuracy of the estimated dose distribution by a 4D dose calculation (4DDC) in comparison to measurements. A single-field plan (0.6 Gy), optimised for a liver patient case (CTV volume: 403cc), was delivered to a homogeneous PMMA phantom and measured by a high resolution scintillating-CCD system at two water equivalent depths. Various motion scenarios (no motion and motions with amplitude of 10 mm and two periods: 3.7 s and 4.4 s) were simulated using a 4D Quasar phantom and logged by an optical tracking system in real-time. Three motion mitigation approaches (single delivery, 6[Formula: see text] layered and volumetric rescanning) were applied, resulting in 10 individual measurements. 4D dose distributions were retrospectively calculated in water by taking into account the delivery log files (retrospective) containing information on the actually delivered spot positions, fluences, and time stamps. Moreover, in order to evaluate the sensitivity of the 4DDC inputs, the corresponding prospective 4DDCs were performed as a comparison, using the estimated time stamps of the spot delivery and repeated periodical motion patterns. 2D gamma analyses and dose-difference-histograms were used to quantify the agreement between measurements and calculations for all pixels with [Formula: see text]5% of the maximum calculated dose. The results show that a mean gamma score of 99.2% with standard deviation 1.0% can be achieved for 3%/3 mm criteria and all scenarios can reach a score of more than 95%. The average area with more than 5% dose difference was 6.2%. Deviations due to input uncertainties were obvious for single scan deliveries but could be smeared out once rescanning was applied. Thus, the deforming grid 4DDC has been demonstrated to be able to predict the complex patterns of 4D dose distributions for PBS proton therapy with high dosimetric and geometric accuracy, and it can be used as a valid clinical tool for 4D treatment planning, motion mitigation selection, and eventually 4D optimisation applications if the correct temporal information is available.

Experimental validation of a deforming grid 4D dose calculation for PBS proton therapy

NASA Astrophysics Data System (ADS)

Krieger, Miriam; Klimpki, Grischa; Fattori, Giovanni; Hrbacek, Jan; Oxley, David; Safai, Sairos; Weber, Damien C.; Lomax, Antony J.; Zhang, Ye

2018-03-01

The aim of this study was to verify the temporal accuracy of the estimated dose distribution by a 4D dose calculation (4DDC) in comparison to measurements. A single-field plan (0.6 Gy), optimised for a liver patient case (CTV volume: 403cc), was delivered to a homogeneous PMMA phantom and measured by a high resolution scintillating-CCD system at two water equivalent depths. Various motion scenarios (no motion and motions with amplitude of 10 mm and two periods: 3.7 s and 4.4 s) were simulated using a 4D Quasar phantom and logged by an optical tracking system in real-time. Three motion mitigation approaches (single delivery, 6× layered and volumetric rescanning) were applied, resulting in 10 individual measurements. 4D dose distributions were retrospectively calculated in water by taking into account the delivery log files (retrospective) containing information on the actually delivered spot positions, fluences, and time stamps. Moreover, in order to evaluate the sensitivity of the 4DDC inputs, the corresponding prospective 4DDCs were performed as a comparison, using the estimated time stamps of the spot delivery and repeated periodical motion patterns. 2D gamma analyses and dose-difference-histograms were used to quantify the agreement between measurements and calculations for all pixels with > 5% of the maximum calculated dose. The results show that a mean gamma score of 99.2% with standard deviation 1.0% can be achieved for 3%/3 mm criteria and all scenarios can reach a score of more than 95%. The average area with more than 5% dose difference was 6.2%. Deviations due to input uncertainties were obvious for single scan deliveries but could be smeared out once rescanning was applied. Thus, the deforming grid 4DDC has been demonstrated to be able to predict the complex patterns of 4D dose distributions for PBS proton therapy with high dosimetric and geometric accuracy, and it can be used as a valid clinical tool for 4D treatment planning, motion mitigation selection, and eventually 4D optimisation applications if the correct temporal information is available.

Fetal bladder catheterization in severe obstructive uropathy before the 24th week of pregnancy.

PubMed

Szaflik, K; Kozarzewski, M; Adamczewski, D

1998-01-01

Fetal obstructive uropathy is simple to diagnose before the 24th week of life. Drainage of the pathologically enlarged fetal bladder avoids development of hydronephrosis and destruction of kidneys and, obviously, prevents development of secondary oligohydramnios and pulmonary hypoplasia. The aim of our study was to evaluate the usefulness of a fetal bladder shunt in cases of obstructive uropathy before the 24th week of gestation. From January 1997 we diagnosed 6 cases of fetal obstructive uropathy before the 24th week of gestation. In all cases oligohydramnios or ahydramnios was also observed. After evaluation of the renal function on the basis of fetal urine samples, we shunted 5 fetuses. After routine preparation of the operative field, a special puncture needle was inserted through the abdominal wall of mother and fetus into the fetal bladder. Through the needle a fetal bladder catheter was inserted between the fetal bladder and the amniotic sac. After shunt placement, fetal urine fills the amniotic sac and the fetal bladder is decompressed. After the procedure, the patients were hospitalized and serial sonographic examinations were performed to evaluate shunt function. Bladder size, presence and size of hydronephrosis, and volume of amniotic fluid were evaluated. The Rocket Medical catheters have an excellent 'shape memory'. All but 1 newborns had a good perinatal outcome. Mean Apgar score was 8 at 1 min, weight at delivery was between 1,700 and 3,100 g. No pulmonary hypoplasia was observed. All deliveries were after the 33rd week of gestation (range 33-38 weeks). The minimum drainage time was 11 weeks, maximum 18 weeks. In 2 cases premature delivery occurred because of premature rupture of the membranes. One newborn died of respiratory distress syndrome. Early bladder drainage (before the 24th week of gestation) enables delivery of newborns with a good perinatal outcome, without pulmonary hypoplasia. This method of therapy limits renal damage and allows time for normal development of the fetal lungs.

Magnetic iron oxide nanoparticles (MIONs) cross-linked natural polymer-based hybrid gel beads: Controlled nano anti-TB drug delivery application.

PubMed

Kesavan, Mookkandi Palsamy; Ayyanaar, Srinivasan; Vijayakumar, Vijayaparthasarathi; Dhaveethu Raja, Jeyaraj; Annaraj, Jamespandi; Sakthipandi, Kathiresan; Rajesh, Jegathalaprathaban

2018-04-01

The nanosized rifampicin (RIF) has been prepared to increase the solubility in aqueous solution, which leads to remarkable enhancement of its bioavailability and their convenient delivery system studied by newly produced nontoxic, biodegradable magnetic iron oxide nanoparticles (MIONs) cross-linked polyethylene glycol hybrid chitosan (mCS-PEG) gel beads. The functionalization of both nano RIF and mCS-PEG gel beads were studied using various spectroscopic and microscopic techniques. The size of prepared nano RIF was found to be 70.20 ± 3.50 nm. The mechanical stability and swelling ratio of the magnetic gel beads increased by the addition of PEG with a maximum swelling ratio of 38.67 ± 0.29 g/g. Interestingly, this magnetic gel bead has dual responsive assets in the nano drug delivery application (pH and the magnetic field). As we expected, magnetic gel beads show higher nano drug releasing efficacy at acidic medium (pH = 5.0) with maximum efficiency of 71.00 ± 0.87%. This efficacy may also be tuned by altering the external magnetic field and the weight percentage (wt%) of PEG. These results suggest that such a dual responsive magnetic gel beads can be used as a potential system in the nano drug delivery applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1039-1050, 2018. © 2017 Wiley Periodicals, Inc.

Sediment delivery after a wildfire

USGS Publications Warehouse

Reneau, Steven L.; Katzman, D.; Kuyumjian, G.A.; Lavine, A.; Malmon, D.V.

2007-01-01

We use a record of sedimentation a small reservoir within the Cerro Grande burn area, New Mexico, to document postfire delivery of ash, other fine-grained sediment carried in suspension within floods, and coarse-grained sediment transported as bedload over a five-year period. Ash content of sediment layers is estimated using fallout 137Cs as a tracer, and ash concentrations are shown to rapidly decrease through a series of moderate-intensity convective storms in the first rainy season after the fire. Over 90% of the ash was delivered to the reservoir in the first year, and ash concentrations in suspended sediment were negligible after the second year. Delivery of the remainder of the fine sediment also declined rapidly after the first year despite the occurrence of higher-intensity storms in the second year. Fine sediment loads after five years remained significantly above prefire averages. Deposition of coarse-grained sediment was irregular in time and was associated with transport by snowmelt runoff of sediment stored along the upstream channel during short-duration summer floods. Coarse sediment delivery in the first four years was strongly correlated with snowmelt volume, suggesting a transport-limited system with abundant available sediment. Transport rates of coarse sediment declined in the fifth year, consistent with a transition to a more stable channel as the accessible sediment supply was depleted and the channel bed coarsened. Maximum impacts from ash and other fine-grained sediment therefore occurred soon after the fire, whereas the downstream impacts from coarse-grained sediment were attenuated by the more gradual process of bedload sediment transport. ?? 2007 Geological Society of America.

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

PubMed

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

2016-01-01

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

Extracellular control of intracellular drug release for enhanced safety of anti-cancer chemotherapy

NASA Astrophysics Data System (ADS)

Zhu, Qian; Qi, Haixia; Long, Ziyan; Liu, Shang; Huang, Zhen; Zhang, Junfeng; Wang, Chunming; Dong, Lei

2016-06-01

The difficulty of controlling drug release at an intracellular level remains a key challenge for maximising drug safety and efficacy. We demonstrate herein a new, efficient and convenient approach to extracellularly control the intracellular release of doxorubicin (DOX), by designing a delivery system that harnesses the interactions between the system and a particular set of cellular machinery. By simply adding a small-molecule chemical into the cell medium, we could lower the release rate of DOX in the cytosol, and thereby increase its accumulation in the nuclei while decreasing its presence at mitochondria. Delivery of DOX with this system effectively prevented DOX-induced mitochondria damage that is the main mechanism of its toxicity, while exerting the maximum efficacy of this anti-cancer chemotherapeutic agent. The present study sheds light on the design of drug delivery systems for extracellular control of intracellular drug delivery, with immediate therapeutic implications.

Baseline tests of the battronic Minivan electric delivery van

NASA Technical Reports Server (NTRS)

Dustin, M. O.; Soltis, R. F.; Bozek, J. M.; Maslowski, E. A.

1977-01-01

An electric passenger vehicle was tested to develop data characterizing the state of the art of electric and hybrid vehicles. The test measured vehicle maximum speed, range at constant speed, range over stop-and-go driving schedules, maximum acceleration, gradeability and limit, road energy consumption, road power, indicated energy consumption, braking capability and battery charge efficiency. The data obtained are to serve as a baseline to compare improvements in electric and hybrid vehicle technologies and to assist in establishing performance standards.

Underwater Communications for Video Surveillance Systems at 2.4 GHz

PubMed Central

Sendra, Sandra; Lloret, Jaime; Jimenez, Jose Miguel; Rodrigues, Joel J.P.C.

2016-01-01

Video surveillance is needed to control many activities performed in underwater environments. The use of wired media can be a problem since the material specially designed for underwater environments is very expensive. In order to transmit the images and videos wirelessly under water, three main technologies can be used: acoustic waves, which do not provide high bandwidth, optical signals, although the effect of light dispersion in water severely penalizes the transmitted signals and therefore, despite offering high transfer rates, the maximum distance is very small, and electromagnetic (EM) waves, which can provide enough bandwidth for video delivery. In the cases where the distance between transmitter and receiver is short, the use of EM waves would be an interesting option since they provide high enough data transfer rates to transmit videos with high resolution. This paper presents a practical study of the behavior of EM waves at 2.4 GHz in freshwater underwater environments. First, we discuss the minimum requirements of a network to allow video delivery. From these results, we measure the maximum distance between nodes and the round trip time (RTT) value depending on several parameters such as data transfer rate, signal modulations, working frequency, and water temperature. The results are statistically analyzed to determine their relation. Finally, the EM waves’ behavior is modeled by a set of equations. The results show that there are some combinations of working frequency, modulation, transfer rate and temperature that offer better results than others. Our work shows that short communication distances with high data transfer rates is feasible. PMID:27782095

Underwater Communications for Video Surveillance Systems at 2.4 GHz.

PubMed

Sendra, Sandra; Lloret, Jaime; Jimenez, Jose Miguel; Rodrigues, Joel J P C

2016-10-23

Video surveillance is needed to control many activities performed in underwater environments. The use of wired media can be a problem since the material specially designed for underwater environments is very expensive. In order to transmit the images and videos wirelessly under water, three main technologies can be used: acoustic waves, which do not provide high bandwidth, optical signals, although the effect of light dispersion in water severely penalizes the transmitted signals and therefore, despite offering high transfer rates, the maximum distance is very small, and electromagnetic (EM) waves, which can provide enough bandwidth for video delivery. In the cases where the distance between transmitter and receiver is short, the use of EM waves would be an interesting option since they provide high enough data transfer rates to transmit videos with high resolution. This paper presents a practical study of the behavior of EM waves at 2.4 GHz in freshwater underwater environments. First, we discuss the minimum requirements of a network to allow video delivery. From these results, we measure the maximum distance between nodes and the round trip time (RTT) value depending on several parameters such as data transfer rate, signal modulations, working frequency, and water temperature. The results are statistically analyzed to determine their relation. Finally, the EM waves' behavior is modeled by a set of equations. The results show that there are some combinations of working frequency, modulation, transfer rate and temperature that offer better results than others. Our work shows that short communication distances with high data transfer rates is feasible.

Nanovesicles for transdermal delivery of felodipine: Development, characterization, and pharmacokinetics

PubMed Central

Yusuf, Mohd; Sharma, Vijay; Pathak, Kamla

2014-01-01

Aim: The research traces development of nanovesicles to attain enhanced transdermal delivery of felodipine and also investigates parameters for optimization of variable membrane compositions containing soya- and egg lecithin and edge activator. Materials and Methods: Rotary evaporation sonication method was employed to obtain tranfersomal formulation that was characterized for vesicle shape and size, polydispersity index (PDI), zeta potential, entrapment and loading efficiency, deformability index and in vitro skin permeation. Results: Spherical nanovesicles of 75.71 ± 5.4 nm with PDI 0.228 and zeta potential of −49.8 were adjudged as the best formulation (MF8). MF8 displayed maximum entrapment and loading efficiency with a high deformability index of 119.68. In vitro permeation across rat skin by MF8 reported 256% enhancement in permeation (flux = 23.72 ± 0.64) when compared with transdermal control formulation and followed zero order kinetics (Case-II). Pharmacokinetic studies revealed that transdermal administration, in contrast to oral delivery provided relatively constant, sustained blood concentration with minimal plasma fluctuation, rapid and prolonged peak time. The relative bioavailability of felodipine was found 358.42% versus oral administration that was well supported by the outcomes of confocal laser scanning microscopic studies that suggested rapid permeation of drugs to across dermal layers. Conclusion: The results conclude that composition variation and method of preparation elicited significant effect on the vesicle characteristic and proved the transcendency of felodipine loaded transfersomes. PMID:25126525

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...

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...

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...

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...

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...

Estimation of maximum transdermal flux of nonionized xenobiotics from basic physicochemical determinants

PubMed Central

Milewski, Mikolaj; Stinchcomb, Audra L.

2012-01-01

An ability to estimate the maximum flux of a xenobiotic across skin is desirable both from the perspective of drug delivery and toxicology. While there is an abundance of mathematical models describing the estimation of drug permeability coefficients, there are relatively few that focus on the maximum flux. This article reports and evaluates a simple and easy-to-use predictive model for the estimation of maximum transdermal flux of xenobiotics based on three common molecular descriptors: logarithm of octanol-water partition coefficient, molecular weight and melting point. The use of all three can be justified on the theoretical basis of their influence on the solute aqueous solubility and the partitioning into the stratum corneum lipid domain. The model explains 81% of the variability in the permeation dataset comprised of 208 entries and can be used to obtain a quick estimate of maximum transdermal flux when experimental data is not readily available. PMID:22702370

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

PubMed

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

2016-07-01

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

Broadband low-dispersion low-nonlinearity photonic crystal fiber dedicated to near-infrared high-power femtosecond pulse delivery

NASA Astrophysics Data System (ADS)

Hoang, Van Thuy; Siwicki, Bartłomiej; Franczyk, Marcin; Stępniewski, Grzegorz; Van, Hieu Le; Long, Van Cao; Klimczak, Mariusz; Buczyński, Ryszard

2018-05-01

A low-dispersion and low-nonlinearity silica photonic crystal fiber is designed and developed. The investigated fiber is effectively single-mode and has low dispersion -20 to 40 ps/nm/km in the 1-1.7 μm wavelength range. The silica PCF can withstand a 1017 nm QCW laser beam with a maximum tested power of 9.1 W. The investigated PCF with NA = 0.15 is suggested as a promising medium for a high-power femtosecond undistorted pulse delivery in the near-infrared region.

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.

SU-E-T-624: Quantitative Evaluation of 2D Versus 3D Dosimetry for Stereotactic Volumetric Modulated Arc Delivery Using COMPASS

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

Vikraman, S; Karrthick, K; Rajesh, T

2014-06-15

Purpose: The purpose of this study was to evaluate quantitatively 2D versus 3D dosimetry for stereotactic volumetric modulated arc delivery using COMPASS with 2D array. Methods: Twenty-five patients CT images and RT structures of different sites like brain, head and neck, thorax, abdomen and spine were taken from Multiplan planning system for this study. All these patients underwent radical stereotactic treatment in Cyberknife. For each patient, linac based VMAT stereotactic plans were generated in Monaco TPS v 3.1 using Elekta Beam Modulator MLC. Dose prescription was in the range of 5-20Gy/fraction.TPS calculated VMAT plan delivery accuracy was quantitatively evaluated withmore » COMPASS measured dose and calculated dose based on DVH metrics. In order to ascertain the potential of COMPASS 3D dosimetry for stereotactic plan delivery, 2D fluence verification was performed with MatriXX using Multicube. Results: For each site, D{sub 9} {sub 5} was achieved with 100% of prescription dose with maximum 0.05SD. Conformity index (CI) was observed closer to 1.15 in all cases. Maximum deviation of 2.62 % was observed for D{sub 9} {sub 5} when compared TPS versus COMPASS measured. Considerable deviations were observed in head and neck cases compare to other sites. The maximum mean and standard deviation for D{sub 9} {sub 5}, average target dose and average gamma were -0.78±1.72, -1.10±1.373 and 0.39±0.086 respectively. Numbers of pixels passing 2D fluence verification were observed as a mean of 99.36% ±0.455 SD with 3% dose difference and 3mm DTA. For critical organs in head and neck cases, significant dose differences were observed in 3D dosimetry while the target doses were matched well within limit in both 2D and 3D dosimetry. Conclusion: The quantitative evaluations of 2D versus 3D dosimetry for stereotactic volumetric modulated plans showed the potential of highlighting the delivery errors. This study reveals that COMPASS 3D dosimetry is an effective tool for patient specific quality assurance compared to 2D fluence verification.« less

Dosimetric and delivery efficiency investigation for treating hepatic lesions with a MLC-equipped robotic radiosurgery–radiotherapy combined system

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

Jin, Lihui, E-mail: lihui.jin@fccc.edu; Price, Robert A.; Wang, Lu

Purpose: The CyberKnife M6 (CK-M6) Series introduced a multileaf collimator (MLC) for extending its capability from stereotactic radiosurgery/stereotactic radiotherapy (SBRT) to conventionally fractionated radiotherapy. This work is to investigate the dosimetric quality of plans that are generated using MLC-shaped beams on the CK-M6, as well as their delivery time, via comparisons with the intensity modulated radiotherapy plans that were clinically used on a Varian Linac for treating hepatic lesions. Methods: Nine patient cases were selected and divided into three groups with three patients in each group: (1) the group-one patients were treated conventionally (25 fractions); (2) the group-two patients weremore » treated with SBRT-like hypofractionation (5 fractions); and (3) the group-three patients were treated similar to group-one patients, but with two planning target volumes (PTVs) and two different prescription dose levels correspondingly. The clinically used plans were generated on the ECLIPSE treatment planning system (TPS) and delivered on a Varian Linac (E-V plans). The multiplan (MP) TPS was used to replan these clinical cases with the MLC as the beam device for the CK-M6 (C-M plans). After plans were normalized to the same PTV dose coverage, comparisons between the C-M and E-V plans were performed based on D{sub 99%} (percentage of prescription dose received by 99% of the PTV), D{sub 0.1cm{sup 3}} (the percentage of prescription dose to 0.1 cm{sup 3} of the PTV), and doses received by critical structures. Then, the delivery times for the C-M plans will be obtained, which are the MP TPS generated estimations assuming having an imaging interval of 60 s. Results: The difference in D{sub 99%} between C-M and E-V plans is +0.6% on average (+ or − indicating a higher or lower dose from C-M plans than from E-V plans) with a range from −4.1% to +3.8%, and the difference in D{sub 0.1cm{sup 3}} was −1.0% on average with a range from −5.1% to +2.9%. The PTV conformity index (CI) for the C-M plans ranges from 1.07 to 1.29 with a mean of 1.19, slightly inferior to the E-V plans, in which the CI ranges from 1.00 to 1.15 with a mean of 1.07. Accounting for all nine patients in three groups, 45% of the critical structures received a lower mean dose for the C-M plans as compared with the E-V plans, and similarly, 48% received a lower maximum dose. Furthermore, the average difference of the mean critical structure dose between the C-M and E-V plans over all critical structures for all patients showed only +2.10% relative to the prescription dose and the similar comparison finds the average difference of the maximum critical structure dose of only +1.24%. The estimated delivery times for the C-M plans on the CK-M6 range from 18 to 24 minutes while they are from 7 to 13.7 min for the E-V plans on the Varian Linac. Conclusions: For treating hepatic lesions, for the C-M plans that are comparable to E-V plans in quality, the times needed to deliver these C-M plans on the CK-M6 are longer than the delivery time for the E-V plans on the Varian Linac, but may be clinically acceptable.« less

Delivery time comparison for intensity-modulated radiation therapy with/without flattening filter: a planning study

NASA Astrophysics Data System (ADS)

Fu, Weihua; Dai, Jianrong; Hu, Yimin; Han, Dongsheng; Song, Yixin

2004-04-01

The treatment delivery time of intensity-modulated radiation therapy (IMRT) with a multileaf collimator (MLC) is generally longer than that of conventional radiotherapy. In theory, removing the flattening filter from the treatment head may reduce the beam-on time by enhancing the output dose rate, and then reduce the treatment delivery time. And in practice, there is a possibility of delivering the required fluence distribution by modulating the unflattened non-uniform fluence distribution. However, the reduction of beam-on time may be discounted by the increase of leaf-travel time and (or) verification-and-recording (V&R) time. Here we investigate the overall effect of flattening filter on the treatment delivery time of IMRT with MLCs implemented in the step and shoot method, as well as with compensators on six hybrid machines. We compared the treatment delivery time with/without flattening filter for ten nasopharynx cases and ten prostate cases by observing the variations of the ratio of the beam-on time, segment number, leaf-travel time and the treatment delivery time with dose rate, leaf speed and V&R time. The results show that, without the flattening filter, the beam-on time reduces for both static MLC and compensator-based techniques; the number of segments and the leaf-travel time increase slightly for the static MLC technique; the relative IMRT treatment delivery time decreases more with lower dose rate, higher leaf speed and shorter V&R overhead time. The absolute treatment delivery time reduction depends on the fraction dose. It is not clinically significant at a fraction dose of 2 Gy for the technique of removing the flattening filter, but becomes significant when the fraction dose is as high as that for radiosurgery.

SU-E-T-629: Prediction of the ViewRay Radiotherapy Treatment Time for Clinical Logistics

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

Liu, S; Wooten, H; Wu, Y

Purpose: An algorithm is developed in our clinic, given a new treatment plan, to predict treatment delivery time for radiation therapy (RT) treatments of patients on ViewRay magnetic resonance-image guided radiation therapy (MR-IGRT) delivery system. This algorithm is necessary for managing patient treatment appointments, and is useful as an indicator to assess the treatment plan complexity. Methods: A patient’s total treatment delivery time, not including time required for localization, may be described as the sum of four components: (1) the treatment initialization time; (2) the total beam-on time; (3) the gantry rotation time; and (4) the multileaf collimator (MLC) motionmore » time. Each of the four components is predicted separately. The total beam-on time can be calculated using both the planned beam-on time and the decay-corrected delivery dose rate. To predict the remaining components, we quantitatively analyze the patient treatment delivery record files. The initialization time is demonstrated to be random since it depends on the final gantry angle and MLC leaf positions of the previous treatment. Based on modeling the relationships between the gantry rotation angles and the corresponding rotation time, and between the furthest MLC leaf moving distance and the corresponding MLC motion time, the total delivery time is predicted using linear regression. Results: The proposed algorithm has demonstrated the feasibility of predicting the ViewRay treatment delivery time for any treatment plan of any patient. The average prediction error is 0.89 minutes or 5.34%, and the maximal prediction error is 2.09 minutes or 13.87%. Conclusion: We have developed a treatment delivery time prediction algorithm based on the analysis of previous patients’ treatment delivery records. The accuracy of our prediction is sufficient for guiding and arranging patient treatment appointments on a daily basis. The predicted delivery time could also be used as an indicator to assess the treatment plan complexity. This work was supported by a research grant from Viewray Inc.« less

Pressures generated in vitro during Stabident intraosseous injections.

PubMed

Whitworth, J M; Ramlee, R A M; Meechan, J G

2005-05-01

To test the hypothesis that the Stabident intraosseous injection is a potentially high-pressure technique, which carries serious risks of anaesthetic cartridge failure. A standard Astra dental syringe was modified to measure the internal pressure of local anaesthetic cartridges during injection. Intra-cartridge pressures were measured at 1 s intervals during slow (approximately 15 s) and rapid (<10 s) injections of 2% Xylocaine with 1:80,000 adrenaline (0.25 cartridge volumes) into air (no tissue resistance), or into freshly prepared Stabident perforation sites in the anterior mandible of freshly culled young and old sheep (against tissue resistance). Each injection was repeated 10 times over 3 days. Absolute maximum pressures generated by each category of injection, mean pressures at 1 s intervals in each series of injections, and standard deviations were calculated. Curves of mean maximum intra-cartridge pressure development with time were plotted for slow and rapid injections, and one-way anova (P<0.05) conducted to determine significant differences between categories of injection. Pressures created when injecting into air were less than those needed to inject into tissue (P<0.001). Fast injection produced greater intra-cartridge pressures than slow delivery (P<0.05). Injection pressures rose more quickly and to higher levels in small, young sheep mandibles than in larger, old sheep mandibles. The absolute maximum intra-cartridge pressure developed during the study was 3.31 MPa which is less than that needed to fracture glass cartridges. Stabident intraosseous injection conducted in accordance with the manufacturer's instructions does not present a serious risk of dangerous pressure build-up in local anaesthetic cartridges.

MRI-Based Computational Model of Heterogeneous Tracer Transport following Local Infusion into a Mouse Hind Limb Tumor

PubMed Central

Magdoom, Kulam Najmudeen; Pishko, Gregory L.; Rice, Lori; Pampo, Chris; Siemann, Dietmar W.; Sarntinoranont, Malisa

2014-01-01

Systemic drug delivery to solid tumors involving macromolecular therapeutic agents is challenging for many reasons. Amongst them is their chaotic microvasculature which often leads to inadequate and uneven uptake of the drug. Localized drug delivery can circumvent such obstacles and convection-enhanced delivery (CED) - controlled infusion of the drug directly into the tissue - has emerged as a promising delivery method for distributing macromolecules over larger tissue volumes. In this study, a three-dimensional MR image-based computational porous media transport model accounting for realistic anatomical geometry and tumor leakiness was developed for predicting the interstitial flow field and distribution of albumin tracer following CED into the hind-limb tumor (KHT sarcoma) in a mouse. Sensitivity of the model to changes in infusion flow rate, catheter placement and tissue hydraulic conductivity were investigated. The model predictions suggest that 1) tracer distribution is asymmetric due to heterogeneous porosity; 2) tracer distribution volume varies linearly with infusion volume within the whole leg, and exponentially within the tumor reaching a maximum steady-state value; 3) infusion at the center of the tumor with high flow rates leads to maximum tracer coverage in the tumor with minimal leakage outside; and 4) increasing the tissue hydraulic conductivity lowers the tumor interstitial fluid pressure and decreases the tracer distribution volume within the whole leg and tumor. The model thus predicts that the interstitial fluid flow and drug transport is sensitive to porosity and changes in extracellular space. This image-based model thus serves as a potential tool for exploring the effects of transport heterogeneity in tumors. PMID:24619021

Real-time tracking of tumor motions and deformations along the leaf travel direction with the aid of a synchronized dynamic MLC leaf sequencer.

PubMed

Tacke, Martin; Nill, Simeon; Oelfke, Uwe

2007-11-21

Advanced radiotherapeutical techniques like intensity-modulated radiation therapy (IMRT) are based on an accurate knowledge of the location of the radiation target. An accurate dose delivery, therefore, requires a method to account for the inter- and intrafractional target motion and the target deformation occurring during the course of treatment. A method to compensate in real time for changes in the position and shape of the target is the use of a dynamic multileaf collimator (MLC) technique which can be devised to automatically arrange the treatment field according to real-time image information. So far, various approaches proposed for leaf sequencers have had to rely on a priori known target motion data and have aimed to optimize the overall treatment time. Since for a real-time dose delivery the target motion is not known a priori, the velocity range of the leading leaves is restricted by a safety margin to c x v(max) while the following leaves can travel with an additional maximum speed to compensate for the respective target movements. Another aspect to be considered is the tongue and groove effect. A uniform radiation field can only be achieved if the leaf movements are synchronized. The method presented in this note is the first to combine a synchronizing sequencer and real-time tracking with a dynamic MLC. The newly developed algorithm is capable of online optimizing the leaf velocities by minimizing the overall treatment time while at the same time it synchronizes the leaf trajectories in order to avoid the tongue and groove effect. The simultaneous synchronization is performed with the help of an online-calculated mid-time leaf trajectory which is common for all leaf pairs and which takes into account the real-time target motion and deformation information.

Online 3D EPID-based dose verification: Proof of concept

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

Spreeuw, Hanno; Rozendaal, Roel, E-mail: r.rozenda

Purpose: Delivery errors during radiotherapy may lead to medical harm and reduced life expectancy for patients. Such serious incidents can be avoided by performing dose verification online, i.e., while the patient is being irradiated, creating the possibility of halting the linac in case of a large overdosage or underdosage. The offline EPID-based 3D in vivo dosimetry system clinically employed at our institute is in principle suited for online treatment verification, provided the system is able to complete 3D dose reconstruction and verification within 420 ms, the present acquisition time of a single EPID frame. It is the aim of thismore » study to show that our EPID-based dosimetry system can be made fast enough to achieve online 3D in vivo dose verification. Methods: The current dose verification system was sped up in two ways. First, a new software package was developed to perform all computations that are not dependent on portal image acquisition separately, thus removing the need for doing these calculations in real time. Second, the 3D dose reconstruction algorithm was sped up via a new, multithreaded implementation. Dose verification was implemented by comparing planned with reconstructed 3D dose distributions delivered to two regions in a patient: the target volume and the nontarget volume receiving at least 10 cGy. In both volumes, the mean dose is compared, while in the nontarget volume, the near-maximum dose (D2) is compared as well. The real-time dosimetry system was tested by irradiating an anthropomorphic phantom with three VMAT plans: a 6 MV head-and-neck treatment plan, a 10 MV rectum treatment plan, and a 10 MV prostate treatment plan. In all plans, two types of serious delivery errors were introduced. The functionality of automatically halting the linac was also implemented and tested. Results: The precomputation time per treatment was ∼180 s/treatment arc, depending on gantry angle resolution. The complete processing of a single portal frame, including dose verification, took 266 ± 11 ms on a dual octocore Intel Xeon E5-2630 CPU running at 2.40 GHz. The introduced delivery errors were detected after 5–10 s irradiation time. Conclusions: A prototype online 3D dose verification tool using portal imaging has been developed and successfully tested for two different kinds of gross delivery errors. Thus, online 3D dose verification has been technologically achieved.« less

Traction force during vacuum extraction: a prospective observational study.

PubMed

Pettersson, K; Ajne, J; Yousaf, K; Sturm, D; Westgren, M; Ajne, G

2015-12-01

To investigate the traction force employed during vacuum extractions. Observational cross-sectional study. Obstetric Department, Karolinska University Hospital, Sweden, and the Swedish National Congress of Obstetrics and Gynaecology, 2013. Two hundred women with vacuum extraction at term and 130 obstetricians participating in a simulated setting. In a normal clinical setting, we used a specially adapted device to measure and record the force used to undertake vacuum extraction. In a subsequent part of the study, the force employed for vacuum extraction by a group of obstetricians in a fictive setting was estimated and objectively measured. Applied force during vacuum extraction in relation to the estimated level of difficulty in the delivery; perinatal diagnoses of asphyxia or head trauma; estimated force compared with objectively measured force employed in the fictive setting. The median (minimum-maximum) peak forces for minimum, average and excessive vacuum extraction in the clinical setting were 176 N (5-360 N), 225 N (115-436 N), and 241 N (164-452 N), respectively. In 34% of cases a force in excess of 216 N was employed. There was no correlation between the umbilical arterial pH at delivery and the traction force employed during extraction. Four cases of mild hypoxic ischaemic encephalopathy were observed, three of which were associated with a delivery whereby excessive traction force was employed during the vacuum extraction. In the fictive setting, the actual exerted force was twice the quantitative estimation. The measured forces in the clinical setting were four times higher than that estimated in the fictive setting. Higher than expected levels of traction force were used for vacuum extraction delivery. As obstetricians tend to underestimate the force applied during vacuum extraction, objective measurement with instantaneous feedback may be valuable in raising awareness. © 2015 Royal College of Obstetricians and Gynaecologists.

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

PubMed

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

2012-08-30

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

Labor patterns in women attempting vaginal birth after cesarean with normal neonatal outcomes.

PubMed

Grantz, Katherine L; Gonzalez-Quintero, Victor; Troendle, James; Reddy, Uma M; Hinkle, Stefanie N; Kominiarek, Michelle A; Lu, Zhaohui; Zhang, Jun

2015-08-01

We sought to describe labor patterns in women with a trial of labor after cesarean (TOLAC) with normal neonatal outcomes. In a retrospective observational study at 12 US centers (2002 through 2008), we examined time interval for each centimeter of cervical dilation and compared labor progression stratified by spontaneous or induced labor in 2892 multiparous women with TOLAC (second delivery) and 56,301 nulliparous women at 37 0/7 to 41 6/7 weeks of gestation. Analyses were performed including women with intrapartum cesarean delivery, and also limiting only to women who delivered vaginally. Labor was induced in 23.4% of TOLAC and 44.1% of nulliparous women (P < .001). Cesarean delivery rates were 57.7% in TOLAC vs 19.0% in nulliparous women (P < .001). Oxytocin was used in 52.4% of TOLAC vs 64.3% of nulliparous women with spontaneous labor (P < .001) and 89.8% of TOLAC vs 91.6% of nulliparous women with induced labor (P = .099); however, TOLAC had lower maximum doses of oxytocin compared to nulliparous women: median (90th percentile): 6 (18) mU/min vs 12 (28) mU/min, respectively (P < .001). Median (95th percentile) labor duration for TOLAC vs nulliparous women with spontaneous labor from 4-10 cm was 0.9 (2.2) hours longer (P = .007). For women who entered labor spontaneously and achieved vaginal delivery, labor patterns for TOLAC were similar to nulliparous women. For induced labor, labor duration for TOLAC vs nulliparous women from 4-10 cm was 1.5 (4.6) hours longer (P < .001). For women who achieved vaginal delivery, labor patterns were slower for induced TOLAC compared to nulliparous women. Labor duration for TOLAC was slower compared to nulliparous labor, particularly for induced labor. By improved understanding of the rates of progress at different points in labor, this new information on labor curves in women undergoing TOLAC, particularly for induction, should help physicians when managing labor. Published by Elsevier Inc.

Hurricane Charley Exposure and Hazard of Preterm Delivery, Florida 2004.

PubMed

Grabich, Shannon C; Robinson, Whitney R; Engel, Stephanie M; Konrad, Charles E; Richardson, David B; Horney, Jennifer A

2016-12-01

Objective Hurricanes are powerful tropical storm systems with high winds which influence many health effects. Few studies have examined whether hurricane exposure is associated with preterm delivery. We aimed to estimate associations between maternal hurricane exposure and hazard of preterm delivery. Methods We used data on 342,942 singleton births from Florida Vital Statistics Records 2004-2005 to capture pregnancies at risk of delivery during the 2004 hurricane season. Maternal exposure to Hurricane Charley was assigned based on maximum wind speed in maternal county of residence. We estimated hazards of overall preterm delivery (<37 gestational weeks) and extremely preterm delivery (<32 gestational weeks) in Cox regression models, adjusting for maternal/pregnancy characteristics. To evaluate heterogeneity among racial/ethnic subgroups, we performed analyses stratified by race/ethnicity. Additional models investigated whether exposure to multiples hurricanes increased hazard relative to exposure to one hurricane. Results Exposure to wind speeds ≥39 mph from Hurricane Charley was associated with a 9 % (95 % CI 3, 16 %) increase in hazard of extremely preterm delivery, while exposure to wind speed ≥74 mph was associated with a 21 % (95 % CI 6, 38 %) increase. Associations appeared greater for Hispanic mothers compared to non-Hispanic white mothers. Hurricane exposure did not appear to be associated with hazard of overall preterm delivery. Exposure to multiple hurricanes did not appear more harmful than exposure to a single hurricane. Conclusions Hurricane exposure may increase hazard of extremely preterm delivery. As US coastal populations and hurricane severity increase, the associations between hurricane and preterm delivery should be further studied.

Methods to model and predict the ViewRay treatment deliveries to aid patient scheduling and treatment planning.

PubMed

Liu, Shi; Wu, Yu; Wooten, H Omar; Green, Olga; Archer, Brent; Li, Harold; Yang, Deshan

2016-03-08

A software tool is developed, given a new treatment plan, to predict treatment delivery time for radiation therapy (RT) treatments of patients on ViewRay magnetic resonance image-guided radiation therapy (MR-IGRT) delivery system. This tool is necessary for managing patient treatment scheduling in our clinic. The predicted treatment delivery time and the assessment of plan complexities could also be useful to aid treatment planning. A patient's total treatment delivery time, not including time required for localization, is modeled as the sum of four components: 1) the treatment initialization time; 2) the total beam-on time; 3) the gantry rotation time; and 4) the multileaf collimator (MLC) motion time. Each of the four components is predicted separately. The total beam-on time can be calculated using both the planned beam-on time and the decay-corrected dose rate. To predict the remain-ing components, we retrospectively analyzed the patient treatment delivery record files. The initialization time is demonstrated to be random since it depends on the final gantry angle of the previous treatment. Based on modeling the relationships between the gantry rotation angles and the corresponding rotation time, linear regression is applied to predict the gantry rotation time. The MLC motion time is calculated using the leaves delay modeling method and the leaf motion speed. A quantitative analysis was performed to understand the correlation between the total treatment time and the plan complexity. The proposed algorithm is able to predict the ViewRay treatment delivery time with the average prediction error 0.22min or 1.82%, and the maximal prediction error 0.89 min or 7.88%. The analysis has shown the correlation between the plan modulation (PM) factor and the total treatment delivery time, as well as the treatment delivery duty cycle. A possibility has been identified to significantly reduce MLC motion time by optimizing the positions of closed MLC pairs. The accuracy of the proposed prediction algorithm is sufficient to support patient treatment appointment scheduling. This developed software tool is currently applied in use on a daily basis in our clinic, and could also be used as an important indicator for treatment plan complexity.

Simulating Local Area Network Protocols with the General Purpose Simulation System (GPSS)

DTIC Science & Technology

1990-03-01

generation 15 3.1.2 Frame delivery . 15 3.2 Model artifices 16 3.3 Model variables 17 3.4 Simulation results 18 4. EXTERNAL PROCEDURES USED IN SIMULATION 19...46 15. Token Ring: Frame generation process 47 16. Token Ring: Frame delivery process 48 17 . Token Ring: Mean transfer delay vs mean throughput 49...assumed to be zero were replaced by the maximum values specified in the ANSI 802.3 standard (viz &MI=6, &M2=3, &M3= 17 , &D1=18, &D2=3, &D4=4, &D7=3, and

Transcranial route of brain targeted delivery of methadone in oil.

PubMed

Pathirana, W; Abhayawardhana, P; Kariyawasam, H; Ratnasooriya, W D

2009-05-01

The unique anatomical arrangement of blood vessels and sinuses in the human skull and the brain, the prevalence of a high density of skin appendages in the scalp, extracranial vessels of the scalp communicating with the brain via emissary veins and most importantly, the way that the scalp is used in Ayurvedic medical system in treating diseases associated with the brain show that a drug could be transcranially delivered and targeted to the brain through the scalp. The present study was to investigate by measuring the antinociceptive effect on rats whether the opioid analgesic methadone could be delivered and targeted to the brain by transcranial delivery route. A non aqueous solution of methadone base in sesame oil was used for the application on the scalp. Animal studies were carried out using six groups of male rats consisting of group 1, the oral control treated with distilled water 1 ml; group 2, the oral positive control treated with methadone hydrochloride solution 316.5 mug/ml; group 3, the negative control treated transcranially with the blank sesame oil 0.2 ml and three test groups 4, 5 and 6 treated with three different dose levels of the transcranial oil formulation of methadone base, 41.6 mug/0.2 ml, 104 mug/0.2 ml and 208 mug/0.2 ml, respectively. The antinociceptive effects were examined by subjecting the rats to the hot plate and tail flick tests. The two higher concentrations of the three transcranial methadone formulations yielded response vs time curves showing nearly equal maximum antinociceptive effects similar to that of the oral positive control. Maximum analgesic effect after transcranial administration was observed between 1st and 2nd h and declined up to 6th hour. The results indicate that the transcranial brain targeted delivery of methadone base in the form of an oil based non aqueous solution results in statistically significant antinociceptive effects under experimental conditions. Therefore, it is possible to deliver central nervous system drugs through the proposed transcranial route when suitably formulated.

'Smart' nanoparticles as drug delivery systems for applications in tumor therapy.

PubMed

Fang, Zhi; Wan, Lin-Yan; Chu, Liang-Yin; Zhang, Yan-Qiong; Wu, Jiang-Feng

2015-01-01

In the therapy of clinical diseases such as cancer, it is important to deliver drugs directly to tumor sites in order to maximize local drug concentration and reduce side effects. This objective may be realized by using 'smart' nanoparticles (NPs) as drug delivery systems, because they enable dramatic conformational changes in response to specific physical/chemical stimuli from the diseased cells for targeted and controlled drug release. In this review, we first briefly summarize the characteristics of 'smart' NPs as drug delivery systems in medical therapy, and then discuss their targeting transport, transmembrane and endosomal escape behaviors. Lastly, we focus on the applications of 'smart' NPs as drug delivery systems for tumor therapy. Biodegradable 'smart' NPs have the potential to achieve maximum efficacy and drug availability at the desired sites, and reduce the harmful side effects for healthy tissues in tumor therapy. It is necessary to select appropriate NPs and modify their characteristics according to treatment strategies of tumor therapy.

WE-DE-BRA-11: A Study of Motion Tracking Accuracy of Robotic Radiosurgery Using a Novel CCD Camera Based End-To-End Test System

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

Wang, L; M Yang, Y; Nelson, B

Purpose: A novel end-to-end test system using a CCD camera and a scintillator based phantom (XRV-124, Logos Systems Int’l) capable of measuring the beam-by-beam delivery accuracy of Robotic Radiosurgery (CyberKnife) was developed and reported in our previous work. This work investigates its application in assessing the motion tracking (Synchrony) accuracy for CyberKnife. Methods: A QA plan with Anterior and Lateral beams (with 4 different collimator sizes) was created (Multiplan v5.3) for the XRV-124 phantom. The phantom was placed on a motion platform (superior and inferior movement), and the plans were delivered on the CyberKnife M6 system using four motion patterns:more » static, Sine- wave, Sine with 15° phase shift, and a patient breathing pattern composed of 2cm maximum motion with 4 second breathing cycle. Under integral recording mode, the time-averaged beam vectors (X, Y, Z) were measured by the phantom and compared with static delivery. In dynamic recording mode, the beam spots were recorded at a rate of 10 frames/second. The beam vector deviation from average position was evaluated against the various breathing patterns. Results: The average beam position of the six deliveries with no motion and three deliveries with Synchrony tracking on ideal motion (sinewave without phase shift) all agree within −0.03±0.00 mm, 0.10±0.04, and 0.04±0.03 in the X, Y, and X directions. Radiation beam width (FWHM) variations are within ±0.03 mm. Dynamic video record showed submillimeter tracking stability for both regular and irregular breathing pattern; however the tracking error up to 3.5 mm was observed when a 15 degree phase shift was introduced. Conclusion: The XRV-124 system is able to provide 3D and 4D targeting accuracy for CyberKnife delivery with Synchrony. The experimental results showed sub-millimeter delivery in phantom with excellent correlation in target to breathing motion. The accuracy was degraded when irregular motion and phase shift was introduced.« less

Discovery and Delivery of Synergistic Chemotherapy Drug Combinations to Tumors

NASA Astrophysics Data System (ADS)

Camacho, Kathryn Militar

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

Misting and fan cooling of the rest area in a dairy barn.

PubMed

Calegari, Ferdinando; Calamari, Luigi; Frazzi, Ermes

2012-03-01

This summer study aimed to evaluate the effect on dairy cows, kept in a free stall barn equipped with fans and sprinklers in the feeding area, of the delivery rate of misters in a cooling system in rest areas with different bedding materials. Thirty cows were divided into two homogenous groups according to milk yield and kept in two pens: one had beds with sand (SAMM) while the other had straw (STLM). Each pen was equipped with 2 fans (Ø 70 cm, 0.50 kW) and 2 misters (delivery rate of 11.2 and 22.5 L/h in STLM and SAMM, respectively) in the rest area. Microclimatic parameters, rectal temperature (RT), breathing rate (BR), milk yield, and some milk traits were recorded. Behavioural routines of the cows (standing and lying) were also continuously recorded during the hotter days. During the trial, two mild-moderate heat waves were observed. During these hotter periods, the daily maximum temperature recorded in the rest areas was 28.9 in SAMM and 31.2 in STLM, and the daily maximum THI was 78.2 in SAMM and 81.5 in STLM. In these periods, the cows in SAMM compared with those in STLM showed lower BR (P < 0.05) and greater rest time (10.2 and 7.8 h/day in SAMM and STLM, respectively). The RT did not differ (38.89 ± 0.29 and 38.88 ± 0.33°C in STLM and SAMM r,espectively). In conclusion, our research suggests that the cooling system using fans plus misters with mild wetting in rest areas with sand as bedding materials reduces heat stress and improves cow comfort.

Misting and fan cooling of the rest area in a dairy barn

NASA Astrophysics Data System (ADS)

Calegari, Ferdinando; Calamari, Luigi; Frazzi, Ermes

2012-03-01

This summer study aimed to evaluate the effect on dairy cows, kept in a free stall barn equipped with fans and sprinklers in the feeding area, of the delivery rate of misters in a cooling system in rest areas with different bedding materials. Thirty cows were divided into two homogenous groups according to milk yield and kept in two pens: one had beds with sand (SAMM) while the other had straw (STLM). Each pen was equipped with 2 fans (Ø 70 cm, 0.50 kW) and 2 misters (delivery rate of 11.2 and 22.5 L/h in STLM and SAMM, respectively) in the rest area. Microclimatic parameters, rectal temperature (RT), breathing rate (BR), milk yield, and some milk traits were recorded. Behavioural routines of the cows (standing and lying) were also continuously recorded during the hotter days. During the trial, two mild-moderate heat waves were observed. During these hotter periods, the daily maximum temperature recorded in the rest areas was 28.9 in SAMM and 31.2 in STLM, and the daily maximum THI was 78.2 in SAMM and 81.5 in STLM. In these periods, the cows in SAMM compared with those in STLM showed lower BR ( P < 0.05) and greater rest time (10.2 and 7.8 h/day in SAMM and STLM, respectively). The RT did not differ (38.89 ± 0.29 and 38.88 ± 0.33°C in STLM and SAMM r,espectively). In conclusion, our research suggests that the cooling system using fans plus misters with mild wetting in rest areas with sand as bedding materials reduces heat stress and improves cow comfort.

Modification of the effect of ambient air pollution on pediatric asthma emergency visits: susceptible subpopulations

PubMed Central

Strickland, Matthew J; Klein, Mitchel; Flanders, W Dana; Chang, Howard H; Mulholland, James A; Tolbert, Paige E; Darrow, Lyndsey A

2016-01-01

Background Children may have differing susceptibility to ambient air pollution concentrations depending on various background characteristics of the children. Methods Using emergency department (ED) data linked with birth records from Atlanta, Georgia, we identified ED visits for asthma or wheeze among children aged 2–16 years from 1 January 2002 through 30 June 2010 (n=109,758). We stratified by preterm delivery, term low birth weight, maternal race, Medicaid status, maternal education, maternal smoking, delivery method, and history of a bronchiolitis ED visit. Population-weighted daily average concentrations were calculated for 1-hour maximum carbon monoxide and nitrogen dioxide; 8-hour maximum ozone; and 24-hour average particulate matter less than 10 microns in diameter, particulate matter less than 2.5 microns in diameter (PM2.5), and the PM2.5 components sulfate, nitrate, ammonium, elemental carbon, and organic carbon, using measurements from stationary monitors. Poisson time-series models were used to estimate rate ratios for associations between three-day moving average pollutant concentrations and daily ED visit counts and to investigate effect-measure modification by the stratification factors. Results Associations between pollutant concentrations and asthma exacerbations were larger among children born preterm and among children born to African American mothers. Stratification by race and preterm status together suggested that both factors affected susceptibility. The largest estimated effect size (for an interquartile-range increase in pollution) was observed for ozone among preterm births to African American mothers: rate ratio=1.138 (95% confidence interval=1.077–1.203). In contrast, the rate ration for the ozone association among full-term births to mothers of other races was 1.025 (0.970–1.083). Conclusions Results support the hypothesis that children vary in their susceptibility to ambient air pollutants. PMID:25192402

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.

43 CFR 418.38 - Maximum allowable diversion.

Code of Federal Regulations, 2010 CFR

2010-10-01

... water right holder the full water entitlement for irrigable eligible acres and includes distribution... deliveries at farm headgates have been approximately 90 percent of entitlements. This practice is expected to... efficiency target for the examples shown in the Newlands Project Water Budget table would be: 285,243 AF and...

43 CFR 418.38 - Maximum allowable diversion.

Code of Federal Regulations, 2011 CFR

2011-10-01

... water right holder the full water entitlement for irrigable eligible acres and includes distribution... deliveries at farm headgates have been approximately 90 percent of entitlements. This practice is expected to... efficiency target for the examples shown in the Newlands Project Water Budget table would be: 285,243 AF and...

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

Liu, X

Purpose: To explore the real-time dose verification method in volumetric modulated arc radiotherapy (VMAT) with a 2D array ion chamber array. Methods: The 2D ion chamber array was fixed on the panel of electronic portal imaging device (EPID). Source-detector distance (SDD)was 140cm. 8mm RW3 solid water was added to the detector panel to achieve maximum readings.The patient plans for esophageal, prostate and liver cancers were selected to deliver on the cylindrical Cheese phantom 5 times in order to validate the reproducibility of doses. Real-time patient transit dose measurements were performed at each fraction. Dose distributions wereevaluated using gamma index criteriamore » of 3mm DTA and 3% dose difference referred to the firsttime Result. Results: The gamma index pass rate in the Cheese phantom were about 98%; The gamma index pass rate for esophageal, liver and prostate cancer patient were about 92%,94%, and 92%, respectively; Gamma pass rate for all single fraction were more than 90%. Conclusion: The 2D array is capable of monitoring the real time transit doses during VMAT delivery. It is helpful to improve the treatment accuracy.« less

Development of a New Technique for the Efficient Delivery of Aerosolized Medications to Infants on Mechanical Ventilation

PubMed Central

Longest, P. Worth; Tian, Geng

2014-01-01

Purpose To evaluate the efficiency of a new technique for delivering aerosols to intubated infants that employs a new Y-connector, access port administration of a dry powder, and excipient enhanced growth (EEG) formulation particles that change size in the airways. Methods A previously developed CFD model combined with algebraic correlations were used to predict delivery system and lung deposition of typical nebulized droplets (MMAD = 4.9 μm) and EEG dry powder aerosols. The delivery system consisted of a Y-connector [commercial (CM); streamlined (SL); or streamlined with access port (SL-port)] attached to a 4-mm diameter endotracheal tube leading to the airways of a 6-month-old infant. Results Compared to the CM device and nebulized aerosol, the EEG approach with an initial 0.9 μm aerosol combined with the SL and SL-port geometries reduced device depositional losses by factors of 3-fold and >10-fold, respectively. With EEG powder aerosols, the SL geometry provided the maximum tracheobronchial deposition fraction (55.7%), whereas the SL-port geometry provided the maximum alveolar (67.6%) and total lung (95.7%) deposition fractions, respectively. Conclusions Provided the aerosol can be administered in the first portion of the inspiration cycle, the proposed new method can significantly improve the deposition of pharmaceutical aerosols in the lungs of intubated infants. PMID:25103332

Development of a new technique for the efficient delivery of aerosolized medications to infants on mechanical ventilation.

PubMed

Longest, P Worth; Tian, Geng

2015-01-01

To evaluate the efficiency of a new technique for delivering aerosols to intubated infants that employs a new Y-connector, access port administration of a dry powder, and excipient enhanced growth (EEG) formulation particles that change size in the airways. A previously developed CFD model combined with algebraic correlations were used to predict delivery system and lung deposition of typical nebulized droplets (MMAD = 4.9 μm) and EEG dry powder aerosols. The delivery system consisted of a Y-connector [commercial (CM); streamlined (SL); or streamlined with access port (SL-port)] attached to a 4-mm diameter endotracheal tube leading to the airways of a 6-month-old infant. Compared to the CM device and nebulized aerosol, the EEG approach with an initial 0.9 μm aerosol combined with the SL and SL-port geometries reduced device depositional losses by factors of 3-fold and >10-fold, respectively. With EEG powder aerosols, the SL geometry provided the maximum tracheobronchial deposition fraction (55.7%), whereas the SL-port geometry provided the maximum alveolar (67.6%) and total lung (95.7%) deposition fractions, respectively. Provided the aerosol can be administered in the first portion of the inspiration cycle, the proposed new method can significantly improve the deposition of pharmaceutical aerosols in the lungs of intubated infants.

Quality assurance of dynamic parameters in volumetric modulated arc therapy.

PubMed

Manikandan, A; Sarkar, B; Holla, R; Vivek, T R; Sujatha, N

2012-07-01

The purpose of this study was to demonstrate quality assurance checks for accuracy of gantry speed and position, dose rate and multileaf collimator (MLC) speed and position for a volumetric modulated arc treatment (VMAT) modality (Synergy S; Elekta, Stockholm, Sweden), and to check that all the necessary variables and parameters were synchronous. Three tests (for gantry position-dose delivery synchronisation, gantry speed-dose delivery synchronisation and MLC leaf speed and positions) were performed. The average error in gantry position was 0.5° and the average difference was 3 MU for a linear and a parabolic relationship between gantry position and delivered dose. In the third part of this test (sawtooth variation), the maximum difference was 9.3 MU, with a gantry position difference of 1.2°. In the sweeping field method test, a linear relationship was observed between recorded doses and distance from the central axis, as expected. In the open field method, errors were encountered at the beginning and at the end of the delivery arc, termed the "beginning" and "end" errors. For MLC position verification, the maximum error was -2.46 mm and the mean error was 0.0153 ±0.4668 mm, and 3.4% of leaves analysed showed errors of >±1 mm. This experiment demonstrates that the variables and parameters of the Synergy S are synchronous and that the system is suitable for delivering VMAT using a dynamic MLC.

Study of the Efficiency of the Hydroporation for Delivery of Plasmid DNA to the Cells on the Model of Toxic Neuropathy.

PubMed

Yudin, M A; Bykov, V N; Nikiforov, A S; Al-Shekhadat, R I; Ivanov, I M; Ustinova, T M

2018-04-01

We compared the efficiency of delivery of plasmid DNA (active ingredient concentration 1 mg/kg) that provides production of nerve growth factor (NGF) after intravenous administration to rats and after administration by hydroporation. The method of hydroporation ensured plasmid penetration into the liver tissue and lengthened the time of its detection in the organ. DNA concentration in 1 h after its introduction by hydroporation or intravenous route was 0.7 and 0.05 ng/mg tissue, respectively. The use of this transfection method ensured preservation of NGF DNA in the liver tissue at a level of 0.24 ng/mg of tissue 1 day after administration of the plasmid construct, while after intravenous administration, expression of the analyzed DNA was not detected in blood and liver samples. After hydroporation, the maximum of relative normalized expression of cDNA (270 rel. units) was observed after 4 h, and after 1 day, this parameter decreased to 35 rel. units. Introduction of plasmid DNA of NGF by hydroporation prevented the development of disorders of neuromuscular conduction in a rats model of toxic neuropathy induced by subacute administration of malathion in a dose of 0.5 LD 50 .

[Survey on menopausal age and menstruation span in women in Pudong district of Shanghai].

PubMed

Chen, Hua; Feng, You-ji; Shu, Hui-min; Lu, Tian-mei; Zhu, Hong-mei; Yang, Bin-lie; Xiong, Miao

2010-06-01

To investigate natural spontaneous menopausal age, menstruation span and their relationship with menarche age and parity in Pudong district of Shanghai. From Jan 2007 to Jul 2008, 15 083 spontaneous menopause women undergoing cervical cancer screening were enrolled in this study. The questionnaire included menarche age, parity, spontaneous menopausal age and menstruation span. Those women were divided into four groups based on age, which were group of 56 - 60, 61 - 65, 66 - 70 and more than 70.Analysis of variance (ANOVA) was used for comparing difference between menopausal age and menstruation span. Multiple factor regressions was used to analyze the relationship between menarche age, parity and menopausal age and menstruation span. (1) Spontaneous menopausal age: the minimum was 29 years old, the maximum was 61 years old, and the mean age was (50.6 ± 3.7) years old. The mean spontaneous menopause age were (50.9 ± 3.4), (50.7 ± 3.7), (50.0 ± 4.1), (49.6 ± 4.0) years in groups of 56 - 60, 61 - 65, 66 - 70 and more than 70 years. With the increasing age range in four groups, the increasing trends of menopausal age were observed, which the difference of 1.36 year was shown between groups of 56 - 60 and more than 70 years. (2) Menstruation span: the mean of menstruation span was (34.3 ± 4.1) years, which the minimal age of 12 years and maximal age of 48 years were recorded. (34.6 ± 3.8), (34.3 ± 4.1), (33.9 ± 4.6), (33.2 ± 4.5) were observed in groups of 56 - 60, 61 - 65, 66 - 70 and more than 70 years. With the increasing age range in four groups, the increasing trends of menstruation span were observed, which the difference of 1.41 year was shown between groups of 56 - 60 and more than 70 years. (3) The impact of menarche age on menopausal age and menstruation span: there was no correlation between menarche age and menopausal age (r = 0.02); however, menstruation span was found to be negatively correlated with the menarche age (r = -0.43). (4) The impact of parity on menopausal age and menstruation span: the mean menopausal age of women who had 1 - 2 deliveries was significantly higher than those had no delivery or more than 3 deliveries (P < 0.05). However, there was no difference in menopausal age between women with 1 and 2 deliveries or between women without delivery and more than 3 deliveries (P > 0.05). Menstruation span of women with 1 delivery was significantly longer that those with more than 1 delivery (P < 0.05), similarly, women with 2 deliveries had longer menstruation span than women without delivery or more than 3 deliveries (P < 0.05). There were no difference in menstruation span between women with more than 3 deliveries and without delivery (P > 0.05). (5) Multifactor regression analysis for menstruation span: menarche age was correlated with menstruation span negatively (r = -0.97, P < 0.001). There was significantly different menstruation span between group of 61 - 65, 66 - 70 or more than 70 years and group of 56 - 60 (r = -0.18, P = 0.020; r = -0.78, P < 0.001 and r = -1.23, P < 0.001). Menstruation span in women with 1 - 2 deliveries was significantly longer than that of women without delivery or more than 3 deliveries. (6) Multifactor logistic analysis of menopausal age: there was no association between menarche age and menopausal age, however, significant differences were found in mean menopausal age between different groups, which show that menopausal age of group 56 - 60 years was significant higher than the other groups, including age-group 61 - 65 years, 66 - 70 years and over 70 years (r = -0.18, P = 0.020; r = -0.78, P < 0.001; r = -1.23, P < 0.001). Menopausal age in women with 1 - 2 deliveries was significantly higher than those of women without delivery or with more than 3 deliveries, however, no difference between women with 1 and 2 deliveries or between women without deliveries and more than 3 deliveries was observed. (1) Menopausal age and menstruation span exhibited increasing trends in Pudong district of Shanghai. (2) Menarche age and parity were the important factors influencing menopausal age and menstruation span. (3) With younger age of menarche, the menstruation span become longer.(4) Deliveries of 1 - 2 times can significantly delay the menopause and prolong menstruation span, however, the multiple deliveries (≥ 3 times) had no significant impact on menopausal age and menstruation span.

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

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

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

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

43 CFR 4.909 - How do I request an extension of time?

Code of Federal Regulations, 2010 CFR

2010-10-01

... purpose, you may obtain an extension of time under this section. (b) You must submit a written request for... Service, a private delivery or courier service, hand delivery or telefax to (703) 235-8349; (2) If you.... Postal Service, a private delivery or courier service or hand delivery so that it is received within 5...

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 dose is negligible.« less

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

Liu, R; Liu, T; Qi, S

Purposes: There has been growing interest in treating breast cancer using VMAT technique. Our goal is to compare the dosimetry and treatment delivery parameters for the left-sided breast cancer treatment using various VMAT platforms from commercially available planning systems. Methods: Five consecutive left-sided breast cancer patients initially treated with conventional 3D-conformal radiotherapy (3DCRT) were selected. Four VMAT plans using most popular treatment planning systems, including Eclipse (Version 11, Varian), Pinnacle (Version 9.8, Philips), Monaco (Version 2.03, Elekta) and helical Tomotherapy (V4.0, Accuray). The same structure set and same planning goals were used for all VMAT plans. The dosimetric parameters includingmore » target coverage and minimum/maximum/mean, dose-volume endpoints for the selected normal structures: the heart, ipsilateral-/contralateral lung and breast, were evaluated. Other dosimetric indices including heterogeneity index (HI) were evaluated. The treatment delivery parameters, such as monitor unit (MUs) and delivery time were also compared. Results: VMAT increases dose homogeneity to the treated volume and reduces the irradiated heart and left-lung volumes. Compared to the 3DCRT technique, all VMAT plans offer better heart and left-lung dose sparing; the mean heart doses were 4.5±1.6(Monaco), 1.2±0.4(Pinnacle), 1.3± (Eclipse) and 5.6±4.4(Tomo), the mean left-lung doses were 5.9±1.5(Monaco), 3.7±0.7(Pinnacle), 1.4± (Eclipse) and 5.2±1.6 (Tomo), while for the 3DCRT plan, the mean heart and left-Lung doses were 2.9±2.0, and 6.8±4.4 (Gy) respectively. The averaged contralateral-breast and lung mean doses were higher in VMAT plans than the 3DCRT plans but were not statistically significant. Among all the VMAT plans, the Pinnacle plans often yield the lowest right-lung/breast mean doses, and slightly better heterogeneity indices that are similar to Tomotherapy plans. Treatment delivery time of the VMAT plans (except helical Tomotherapy IMRT) is estimated to be comparable with the conventional 3DCRT. Conclusion: VMAT achieves equal or better PTV coverage and comparable OARs sparing compared to the conventional 3DCRT techniques.« less

SU-E-T-508: End to End Testing of a Prototype Eclipse Module for Planning Modulated Arc Therapy On the Siemens Platform

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

Huang, L; Sarkar, V; Spiessens, S

2014-06-01

Purpose: The latest clinical implementation of the Siemens Artiste linac allows for delivery of modulated arcs (mARC) using full-field flattening filter free (FFF) photon beams. The maximum doserate of 2000 MU/min is well suited for high dose treatments such as SBRT. We tested and report on the performance of a prototype Eclipse TPS module supporting mARC capability on the Artiste platform. Method: our spine SBRT patients originally treated with 12/13 field static-gantry IMRT (SGIMRT) were chosen for this study. These plans were designed to satisfy RTOG0631 guidelines with a prescription of 16Gy in a single fraction. The cases were re-plannedmore » as mARC plans in the prototype Eclipse module using the 7MV FFF beam and required to satisfy RTOG0631 requirements. All plans were transferred from Eclipse, delivered on a Siemens Artiste linac and dose-validated using the Delta4 system. Results: All treatment plans were straightforwardly developed, in timely fashion, without challenge or inefficiency using the prototype module. Due to the limited number of segments in a single arc, mARC plans required 2-3 full arcs to yield plan quality comparable to SGIMRT plans containing over 250 total segments. The average (3%/3mm) gamma pass-rate for all arcs was 98.5±1.1%, thus demonstrating both excellent dose prediction by the AAA dose algorithm and excellent delivery fidelity. Mean delivery times for the mARC plans(10.5±1.7min) were 50-70% lower than the SGIMRT plans(26±2min), with both delivered at 2000 MU/min. Conclusion: A prototype Eclipse module capable of planning for Burst Mode modulated arc delivery on the Artiste platform has been tested and found to perform efficiently and accurately for treatment plan development and delivered-dose prediction. Further investigation of more treatment sites is being carried out and data will be presented.« less

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

Wu, J; Hill, G; Spiegel, J

Purpose: To investigate the clinical and dosimetric benefits of automatic gating of left breast mixed with breath-hold technique. Methods: Two Active Breathing Control systems, ABC2.0 and ABC3.0, were used during simulation and treatment delivery. The two systems are different such that ABC2.0 is a breath-hold system without beam control capability, while ABC3.0 has capability in both breath-hold and beam gating. At simulation, each patient was scanned twice: one with free breathing (FB) and one with breath hold through ABC. Treatment plan was generated on the CT with ABC. The same plan was also recalculated on the CT with FB. Thesemore » two plans were compared to assess plan quality. For treatments with ABC2.0, beams with MU > 55 were manually split into multiple subfields. All subfields were identical and shared the total MU. For treatment with ABC3.0, beam splitting was unnecessary. Instead, treatment was delivered in gating mode mixed with breath-hold technique. Treatment delivery efficiency using the two systems was compared. Results: The prescribed dose was 50.4Gy at 1.8Gy/fraction. The maximum heart dose averaged over 10 patients was 46.0±2.5Gy and 24.5±12.2Gy for treatments with FB and with ABC respectively. The corresponding heart V10 was 13.2±3.6% and 1.0±1.6% respectively. The averaged MUs were 99.8±7.5 for LMT, 99.2±9.4 for LLT. For treatment with ABC2.0, normally the original beam was split into 2 subfields. The averaged total time to delivery all beams was 4.3±0.4min for treatments with ABC2.0 and 3.3±0.6min for treatments with ABC3.0 in gating mode. Conclusion: Treatment with ABC tremendously reduced heart dose. Compared to treatments with ABC2.0, gating with ABC3.0 reduced the total treatment time by 23%. Use of ABC3.0 improved the delivery efficiency, and eliminated the possibility of mistreatments. The latter may happen with ABC2.0 where beam is not terminated when breath signal falls outside of the treatment window.« less

Is volumetric modulated arc therapy with constant dose rate a valid option in radiation therapy for head and neck cancer patients?

PubMed

Didona, Annamaria; Lancellotta, Valentina; Zucchetti, Claudio; Panizza, Bianca Moira; Frattegiani, Alessandro; Iacco, Martina; Di Pilato, Anna Concetta; Saldi, Simonetta; Aristei, Cynthia

2018-01-01

Intensity-modulated radiotherapy (IMRT) improves dose distribution in head and neck (HN) radiation therapy. Volumetric-modulated arc therapy (VMAT), a new form of IMRT, delivers radiation in single or multiple arcs, varying dose rates (VDR-VMAT) and gantry speeds, has gained considerable attention. Constant dose rate VMAT (CDR-VMAT) associated with a fixed gantry speed does not require a dedicated linear accelerator like VDR-VMAT. The present study explored the feasibility, efficiency and delivery accuracy of CDR-VMAT, by comparing it with IMRT and VDR-VMAT in treatment planning for HN cancer. Step and shoot IMRT (SS-IMRT), CDR-VMAT and VDR-VMAT plans were created for 15 HN cancer patients and were generated by Pinnacle 3 TPS (v 9.8) using 6 MV photon energy. Three PTVs were defined to receive respectively prescribed doses of 66 Gy, 60 Gy and 54 Gy, in 30 fractions. Organs at risk (OARs) included the mandible, spinal cord, brain stem, parotids, salivary glands, esophagus, larynx and thyroid. SS-IMRT plans were based on 7 co-planar beams at fixed gantry angles. CDR-VMAT and VDR-VMAT plans, generated by the SmartArc module, used a 2-arc technique: one clockwise from 182° to 178° and the other one anti-clockwise from 178° to 182°. Comparison parameters included dose distribution to PTVs ( D mean , D 2% , D 50% , D 95% , D 98% and Homogeneity Index), maximum or mean doses to OARs, specific dose-volume data, the monitor units and treatment delivery times. Compared with SS-IMRT, CDR-VMAT significantly reduced the maximum doses to PTV1 and PTV2 and significantly improved all PTV3 parameters, except D 98% and D 95% . It significantly spared parotid and submandibular glands and was associated with a lower D mean to the larynx. Compared with VDR-VMAT, CDR-VMAT was linked to a significantly better D mean , to the PTV3 but results were worse for the parotids, left submandibular gland, esophagus and mandible. Furthermore, the D mean to the larynx was also worse. Compared with SS-IMRT and VDR-VMAT, CDR-VMAT was associated with higher average monitor unit values and significantly shorter average delivery times. CDR-VMAT appeared to be a valid option in Radiation Therapy Centers that lack a dedicated linear accelerator for volumetric arc therapy with variable dose-rates and gantry velocities, and are unwilling or unable to sanction major expenditure at present but want to adopt volumetric techniques.

Methods to model and predict the ViewRay treatment deliveries to aid patient scheduling and treatment planning

PubMed Central

Liu, Shi; Wu, Yu; Wooten, H. Omar; Green, Olga; Archer, Brent; Li, Harold

2016-01-01

A software tool is developed, given a new treatment plan, to predict treatment delivery time for radiation therapy (RT) treatments of patients on ViewRay magnetic resonance image‐guided radiation therapy (MR‐IGRT) delivery system. This tool is necessary for managing patient treatment scheduling in our clinic. The predicted treatment delivery time and the assessment of plan complexities could also be useful to aid treatment planning. A patient's total treatment delivery time, not including time required for localization, is modeled as the sum of four components: 1) the treatment initialization time; 2) the total beam‐on time; 3) the gantry rotation time; and 4) the multileaf collimator (MLC) motion time. Each of the four components is predicted separately. The total beam‐on time can be calculated using both the planned beam‐on time and the decay‐corrected dose rate. To predict the remain‐ing components, we retrospectively analyzed the patient treatment delivery record files. The initialization time is demonstrated to be random since it depends on the final gantry angle of the previous treatment. Based on modeling the relationships between the gantry rotation angles and the corresponding rotation time, linear regression is applied to predict the gantry rotation time. The MLC motion time is calculated using the leaves delay modeling method and the leaf motion speed. A quantitative analysis was performed to understand the correlation between the total treatment time and the plan complexity. The proposed algorithm is able to predict the ViewRay treatment delivery time with the average prediction error 0.22 min or 1.82%, and the maximal prediction error 0.89 min or 7.88%. The analysis has shown the correlation between the plan modulation (PM) factor and the total treatment delivery time, as well as the treatment delivery duty cycle. A possibility has been identified to significantly reduce MLC motion time by optimizing the positions of closed MLC pairs. The accuracy of the proposed prediction algorithm is sufficient to support patient treatment appointment scheduling. This developed software tool is currently applied in use on a daily basis in our clinic, and could also be used as an important indicator for treatment plan complexity. PACS number(s): 87.55.N PMID:27074472

48 CFR 52.211-9 - Desired and Required Time of Delivery.

Code of Federal Regulations, 2014 CFR

2014-10-01

... following clause: Desired and Required Time of Delivery (JUN 1997) (a) The Government desires delivery to be... or specific periods above are based on the assumption that the Government will make award by...

48 CFR 52.211-9 - Desired and Required Time of Delivery.

Code of Federal Regulations, 2011 CFR

2011-10-01

... following clause: Desired and Required Time of Delivery (JUN 1997) (a) The Government desires delivery to be... or specific periods above are based on the assumption that the Government will make award by...

48 CFR 52.211-9 - Desired and Required Time of Delivery.

Code of Federal Regulations, 2013 CFR

2013-10-01

... following clause: Desired and Required Time of Delivery (JUN 1997) (a) The Government desires delivery to be... or specific periods above are based on the assumption that the Government will make award by...

48 CFR 52.211-9 - Desired and Required Time of Delivery.

Code of Federal Regulations, 2012 CFR

2012-10-01

... following clause: Desired and Required Time of Delivery (JUN 1997) (a) The Government desires delivery to be... or specific periods above are based on the assumption that the Government will make award by...

48 CFR 52.211-9 - Desired and Required Time of Delivery.

Code of Federal Regulations, 2010 CFR

2010-10-01

... following clause: Desired and Required Time of Delivery (JUN 1997) (a) The Government desires delivery to be... or specific periods above are based on the assumption that the Government will make award by...

Convection-enhancement delivery of platinum-based drugs and Lipoplatin™ to optimize the concomitant effect with radiotherapy in F98 glioma rat model

PubMed Central

Shi, Minghan; Fortin, David; Sanche, Léon; Paquette, Benoit

2015-01-01

The prognosis for patients with glioblastoma remains poor with current treatments. Although platinum based drugs are sometimes offered at relapse, their efficacy in this setting is still disputed. In this study, we use convection-enhanced delivery (CED) to deliver the platinum-based drugs (cisplatin, carboplatin, and Lipoplatin™-liposomal formulation of cisplatin) directly into the tumor of F98 glioma-bearing rats that were subsequently treated with γ radiation (15 Gy). CED increased by factors varying between 17 and 111, the concentration of these platinum-based drugs in the brain tumor compared to intra-venous (i.v.) administration, and by 9- to 34-fold, when compared to intra-arterial (i.a.) administration. Furthermore, CED resulted in a better systemic tolerance to platinum drugs compared to their i.a. injection. Among the drugs tested, carboplatin showed the highest maximum tolerated dose (MTD). Treatment with carboplatin resulted in the best median survival time (MeST) (38.5 days), which was further increased by the addition of radiotherapy (54.0 days). Although the DNA-bound platinum adduct were higher at 4 h after CED than 24 h for carboplatin group, combination with radiotherapy led to similar improvement of median survival time. However, less toxicity was observed in animals irradiated 24 h after CED-based chemotherapy. In conclusion, CED increased the accumulation of platinum drugs in tumor, reduced the toxicity, and resulted in a higher median survival time. The best treatment was obtained in animals treated with carboplatin and irradiated 24 h later. PMID:25784204

Convection-enhancement delivery of platinum-based drugs and Lipoplatin(TM) to optimize the concomitant effect with radiotherapy in F98 glioma rat model.

PubMed

Shi, Minghan; Fortin, David; Sanche, Léon; Paquette, Benoit

2015-06-01

The prognosis for patients with glioblastoma remains poor with current treatments. Although platinum-based drugs are sometimes offered at relapse, their efficacy in this setting is still disputed. In this study, we use convection-enhanced delivery (CED) to deliver the platinum-based drugs (cisplatin, carboplatin, and Lipoplatin(TM) - liposomal formulation of cisplatin) directly into the tumor of F98 glioma-bearing rats that were subsequently treated with γ radiation (15 Gy). CED increased by factors varying between 17 and 111, the concentration of these platinum-based drugs in the brain tumor compared to intra-venous (i.v.) administration, and by 9- to 34-fold, when compared to intra-arterial (i.a.) administration. Furthermore, CED resulted in a better systemic tolerance to platinum drugs compared to their i.a. injection. Among the drugs tested, carboplatin showed the highest maximum tolerated dose (MTD). Treatment with carboplatin resulted in the best median survival time (MeST) (38.5 days), which was further increased by the addition of radiotherapy (54.0 days). Although the DNA-bound platinum adduct were higher at 4 h after CED than 24 h for carboplatin group, combination with radiotherapy led to similar improvement of median survival time. However, less toxicity was observed in animals irradiated 24 h after CED-based chemotherapy. In conclusion, CED increased the accumulation of platinum drugs in tumor, reduced the toxicity, and resulted in a higher median survival time. The best treatment was obtained in animals treated with carboplatin and irradiated 24 h later.

Job shop scheduling model for non-identic machine with fixed delivery time to minimize tardiness

NASA Astrophysics Data System (ADS)

Kusuma, K. K.; Maruf, A.

2016-02-01

Scheduling non-identic machines problem with low utilization characteristic and fixed delivery time are frequent in manufacture industry. This paper propose a mathematical model to minimize total tardiness for non-identic machines in job shop environment. This model will be categorized as an integer linier programming model and using branch and bound algorithm as the solver method. We will use fixed delivery time as main constraint and different processing time to process a job. The result of this proposed model shows that the utilization of production machines can be increase with minimal tardiness using fixed delivery time as constraint.

Mitigating the risk of food handling in the home-delivered meal program.

PubMed

Namkung, Young; Ismail, Joseph A; Almanza, Barbara A; Nelson, Douglas C

2007-02-01

The purpose of this cross-sectional study was to examine the length of time between packing and delivery of home-delivered meals, and the extent of foodborne illness risk to the elderly. Procedures to mitigate that risk were also evaluated. Researchers surveyed 95 drivers from home-delivered meal preparation sites in six states across the United States to determine the average length of time that passed during packing, loading, leaving, and delivery. The efficiency of various risk mitigation methods were evaluated and used to adjust the actual delivery time. Total average delivery time from packing to last delivery was 1.92 hours. This study suggests that the risk associated with the actual 1.92 hours of total delivery time could be mitigated to represent approximately 1.55 hours of effective time with proper packing and holding conditions. This methodology proposes a single measure for evaluating the effectiveness of various handling procedures associated with distributing home-delivered meals, which can be utilized to evaluate overall risk when combined with in-house preparation and client-handling behaviors.

The dosimetric impact of inversely optimized arc radiotherapy plan modulation for real-time dynamic MLC tracking delivery.

PubMed

Falk, Marianne; Larsson, Tobias; Keall, Paul; Chul Cho, Byung; Aznar, Marianne; Korreman, Stine; Poulsen, Per; Munck Af Rosenschold, Per

2012-03-01

Real-time dynamic multileaf collimator (MLC) tracking for management of intrafraction tumor motion can be challenging for highly modulated beams, as the leaves need to travel far to adjust for target motion perpendicular to the leaf travel direction. The plan modulation can be reduced by using a leaf position constraint (LPC) that reduces the difference in the position of adjacent MLC leaves in the plan. The purpose of this study was to investigate the impact of the LPC on the quality of inversely optimized arc radiotherapy plans and the effect of the MLC motion pattern on the dosimetric accuracy of MLC tracking delivery. Specifically, the possibility of predicting the accuracy of MLC tracking delivery based on the plan modulation was investigated. Inversely optimized arc radiotherapy plans were created on CT-data of three lung cancer patients. For each case, five plans with a single 358° arc were generated with LPC priorities of 0 (no LPC), 0.25, 0.5, 0.75, and 1 (highest possible LPC), respectively. All the plans had a prescribed dose of 2 Gy × 30, used 6 MV, a maximum dose rate of 600 MU/min and a collimator angle of 45° or 315°. To quantify the plan modulation, an average adjacent leaf distance (ALD) was calculated by averaging the mean adjacent leaf distance for each control point. The linear relationship between the plan quality [i.e., the calculated dose distributions and the number of monitor units (MU)] and the LPC was investigated, and the linear regression coefficient as well as a two tailed confidence level of 95% was used in the evaluation. The effect of the plan modulation on the performance of MLC tracking was tested by delivering the plans to a cylindrical diode array phantom moving with sinusoidal motion in the superior-inferior direction with a peak-to-peak displacement of 2 cm and a cycle time of 6 s. The delivery was adjusted to the target motion using MLC tracking, guided in real-time by an infrared optical system. The dosimetric results were evaluated using gamma index evaluation with static target measurements as reference. The plan quality parameters did not depend significantly on the LPC (p ≥ 0.066), whereas the ALD depended significantly on the LPC (p < 0.001). The gamma index failure rate depended significantly on the ALD, weighted to the percentage of the beam delivered in each control point of the plan (ALD(w)) when MLC tracking was used (p < 0.001), but not for delivery without MLC tracking (p ≥ 0.342). The gamma index failure rate with the criteria of 2% and 2 mm was decreased from > 33.9% without MLC tracking to <31.4% (LPC 0) and <2.2% (LPC 1) with MLC tracking. The results indicate that the dosimetric robustness of MLC tracking delivery of an inversely optimized arc radiotherapy plan can be improved by incorporating leaf position constraints in the objective function without otherwise affecting the plan quality. The dosimetric robustness may be estimated prior to delivery by evaluating the ALD(w) of the plan.

Shot sequencing based on biological equivalent dose considerations for multiple isocenter Gamma Knife radiosurgery.

PubMed

Ma, Lijun; Lee, Letitia; Barani, Igor; Hwang, Andrew; Fogh, Shannon; Nakamura, Jean; McDermott, Michael; Sneed, Penny; Larson, David A; Sahgal, Arjun

2011-11-21

Rapid delivery of multiple shots or isocenters is one of the hallmarks of Gamma Knife radiosurgery. In this study, we investigated whether the temporal order of shots delivered with Gamma Knife Perfexion would significantly influence the biological equivalent dose for complex multi-isocenter treatments. Twenty single-target cases were selected for analysis. For each case, 3D dose matrices of individual shots were extracted and single-fraction equivalent uniform dose (sEUD) values were determined for all possible shot delivery sequences, corresponding to different patterns of temporal dose delivery within the target. We found significant variations in the sEUD values among these sequences exceeding 15% for certain cases. However, the sequences for the actual treatment delivery were found to agree (<3%) and to correlate (R² = 0.98) excellently with the sequences yielding the maximum sEUD values for all studied cases. This result is applicable for both fast and slow growing tumors with α/β values of 2 to 20 according to the linear-quadratic model. In conclusion, despite large potential variations in different shot sequences for multi-isocenter Gamma Knife treatments, current clinical delivery sequences exhibited consistent biological target dosing that approached that maximally achievable for all studied cases.

Regression of recurrent malignant gliomas with convection-enhanced delivery of topotecan.

PubMed

Bruce, Jeffrey N; Fine, Robert L; Canoll, Peter; Yun, Jonathan; Kennedy, Benjamin C; Rosenfeld, Steven S; Sands, Stephen A; Surapaneni, Krishna; Lai, Rose; Yanes, Candix L; Bagiella, Emilia; DeLaPaz, Robert L

2011-12-01

Convection-enhanced delivery of chemotherapeutics for the treatment of malignant glioma is a technique that delivers drugs directly into a tumor and the surrounding interstitium through continuous, low-grade positive-pressure infusion. This allows high local concentrations of drug while overcoming the limitations imposed by toxicity and the blood-brain barrier in systemic therapies that prevent the use of many potentially effective drugs. To examine the safety profile of a conventional chemotherapeutic agent, topotecan, via convection-enhanced delivery in the treatment of recurrent malignant gliomas and secondarily to assess radiographic response and survival. We performed a prospective, dose-escalation phase Ib study of the topoisomerase-I inhibitor topotecan given by convection-enhanced delivery in patients with recurrent malignant gliomas. Significant antitumor activity as described by radiographic changes and prolonged overall survival with minimal drug-associated toxicity was demonstrated. A maximum tolerated dose was established for future phase II studies. Topotecan by convection-enhanced delivery has significant antitumor activity at concentrations that are nontoxic to normal brain. The potential for use of this therapy as a generally effective treatment option for malignant gliomas will be tested in subsequent phase II and III trials.

Distributed network scheduling

NASA Technical Reports Server (NTRS)

Clement, Bradley J.; Schaffer, Steven R.

2004-01-01

Distributed Network Scheduling is the scheduling of future communications of a network by nodes in the network. This report details software for doing this onboard spacecraft in a remote network. While prior work on distributed scheduling has been applied to remote spacecraft networks, the software reported here focuses on modeling communication activities in greater detail and including quality of service constraints. Our main results are based on a Mars network of spacecraft and include identifying a maximum opportunity of improving traverse exploration rate a factor of three; a simulation showing reduction in one-way delivery times from a rover to Earth from as much as 5 to 1.5 hours; simulated response to unexpected events averaging under an hour onboard; and ground schedule generation ranging from seconds to 50 minutes for 15 to 100 communication goals.

Interactive Learning During Solar Maximum

NASA Technical Reports Server (NTRS)

Ashour-Abdalla, Maha; Curtis, Steven (Technical Monitor)

2001-01-01

The goal of this project is to develop and distribute e-educational material for space science during times of solar activity that emphasizes underlying basic science principles of solar disturbances and their effects on Earth. This includes materials such as simulations, animations, group projects and other on-line materials to be used by students either in high school or at the introductory college level. The on-line delivery tool originally intended to be used is known as Interactive Multimedia Education at a Distance (IMED), which is a web-based software system used at UCLA for interactive distance learning. IMED is a password controlled system that allows students to access text, images, bulletin boards, chat rooms, animation, simulations and individual student web sites to study science and to collaborate on group projects.

Sodium Dodecyl Sulphate-Supported Nanocomposite as Drug Carrier System for Controlled Delivery of Ondansetron.

PubMed

Sharma, Gaurav; Naushad, Mu; Thakur, Bharti; Kumar, Amit; Negi, Poonam; Saini, Reena; Chahal, Anterpreet; Kumar, Ashok; Stadler, Florian J; Aqil, U M H

2018-02-27

Sodium dodecyl sulphate-supported iron silicophosphate (SDS/FeSP) nanocomposite was successfully fabricated by the co-precipitation method. The SDS/FeSP nanocomposite was investigated as a drug carrier for ondansetron. The cumulative drug release of ondansetron was observed at various pH values for different time intervals, i.e., from 20 min to 48 h. A ranking of the drug release was observed at different pHs; pH 2.2 > saline (pH 5.5) > pH 7.4 > pH 9.4 > distilled water. Maximum release of encapsulated drug was found to be about 45.38% at pH 2.2. The cell viability tests of SDS/FeSP nanocomposite concluded that SDS/FeSP nanocomposite was non-cytotoxic in nature.

Baseline tests of the power-train electric delivery van

NASA Technical Reports Server (NTRS)

Lumannick, S.; Dustin, M. O.; Bozek, J. M.

1977-01-01

Vehicle maximum speed, range at constant speed, range over stop-and-go driving schedules, maximum acceleration, gradeability, gradeability limit, road energy consumption, road power, indicated energy consumption, braking capability, battery charger efficiency, and battery characteristics were determined for a modified utility van powered by sixteen 6-volt batteries connected in series. A chopper controller actuated by a foot accelerator pedal changes the voltage applied to the 22-kilowatt (30-hp) series-wound drive motor. In addition to the conventional hydraulic braking system, the vehicle has hydraulic regenerative braking. Cycle tests and acceleration tests were conducted with and without hydraulic regeneration.

Quantitative evaluation of pregnant women delivery status' records in Akure, Nigeria.

PubMed

Adejumo, Adebowale O; Suleiman, Esivue A; Okagbue, Hilary I; Oguntunde, Pelumi E; Odetunmibi, Oluwole A

2018-02-01

In this data article, monthly records (datasets) of total delivery, normal delivery, delivery through Caesarean section and number of still births from pregnant women in Akure, the capital city of Ondo state Nigeria, for a period of ten years, between January 2007 and December 2016 were considered. Correlational and time series analyses were conducted on the monthly records of total delivery, normal delivery (delivery through woman virginal), delivery through Caesarean section, and number of still births, in order to observe the patterns each of these indicators follows and to recommend appropriate model for forecasting their future values. The data were obtained in raw form from State Specialist Hospital (SSH), Akure, Ondo state, Nigeria. A clear description and variation in each of these indicators (total delivery, normal delivery, caesarean section, and still births) were considered separately using descriptive statistics and box plots. Different models were also proposed for each of these indicators using time series models.

Starting time for induction of labor and the risk for night-time delivery.

PubMed

Thorsell, M; Lyrenäs, S; Andolf, E; Kaijser, M

2011-08-01

To analyze if starting time for labor induction affected the risk of night-time delivery, and to evaluate to what extent the risk was influenced by Bishop score at start of induction, mode of induction, and parity. A retrospective cohort study of women who delivered at Danderyd Hospital, Stockholm, Sweden, 2002-2006, comprising 1940 women induced by Dinoprostone (PGE(2)) or transcervical balloon catheter (BARD). Risks for night-time delivery were calculated as absolute risk and Odds Ratios by unconditional logistic regression using induction of labor in the morning as reference. For nulliparae with Bishop score 0-3 induced by BARD, odds ratios for night-time delivery were 0.42 (95% C.I. 0.19-0.93) and 0.09 (95% C.I. 0.02-0.47) when inductions started in the afternoon and evening, respectively, compared to inductions starting in the morning For multiparae, however, the risk of night-time delivery was highest if induction started in the evening. Compared to inductions started in the morning, odds ratios for night-time delivery were 3.53 (95% C.I. 2.57-4.83) and 8.49 (95% C.I. 4.45-16.19) for induction starting in the afternoon and evening, respectively. Starting time of labor induction affects the risk of giving birth at night. For nulliparae induced by BARD, starting the induction in the evening instead of during the day may reduce the number of night-time deliveries substantially. For multiparae, however, our data suggest that induction of labor should take place in the morning. Copyright © 2011 Elsevier B.V. All rights reserved.

Power Delivery from an Actual Thermoelectric Generation System

NASA Astrophysics Data System (ADS)

Kaibe, Hiromasa; Kajihara, Takeshi; Nagano, Kouji; Makino, Kazuya; Hachiuma, Hirokuni; Natsuume, Daisuke

2014-06-01

Similar to photovoltaic (PV) and fuel cells, thermoelectric generators (TEGs) supply direct-current (DC) power, essentially requiring DC/alternating current (AC) conversion for delivery as electricity into the grid network. Use of PVs is already well established through power conditioning systems (PCSs) that enable DC/AC conversion with maximum-power-point tracking, which enables commercial use by customers. From the economic, legal, and regulatory perspectives, a commercial PCS for PVs should also be available for TEGs, preferably as is or with just simple adjustment. Herein, we report use of a PV PCS with an actual TEG. The results are analyzed, and proper application for TEGs is proposed.

49 CFR 180.416 - Discharge system inspection and maintenance program for cargo tanks transporting liquefied...

Code of Federal Regulations, 2010 CFR

2010-10-01

... with a unique identification number and maximum working pressure. (c) Post-delivery hose check. After... during the unloading. (d) Monthly inspections and tests. (1) The operator must visually inspect each... operator must actuate all emergency discharge control devices designed to close the internal self-closing...

Challenges of Video-Conferencing Teaching and Effective Teaching Methods

ERIC Educational Resources Information Center

Fitzgibbon, Paula

2003-01-01

Higher educational institutions are increasingly called upon to make cost-cutting decisions in the types of courses offered, the maximum number of students allowed per section and course delivery modes. Lever (1992) says that this "doing more with less" is one of the core challenges facing community colleges and universities. All of us…

A system for EPID-based real-time treatment delivery verification during dynamic IMRT treatment.

PubMed

Fuangrod, Todsaporn; Woodruff, Henry C; van Uytven, Eric; McCurdy, Boyd M C; Kuncic, Zdenka; O'Connor, Daryl J; Greer, Peter B

2013-09-01

To design and develop a real-time electronic portal imaging device (EPID)-based delivery verification system for dynamic intensity modulated radiation therapy (IMRT) which enables detection of gross treatment delivery errors before delivery of substantial radiation to the patient. The system utilizes a comprehensive physics-based model to generate a series of predicted transit EPID image frames as a reference dataset and compares these to measured EPID frames acquired during treatment. The two datasets are using MLC aperture comparison and cumulative signal checking techniques. The system operation in real-time was simulated offline using previously acquired images for 19 IMRT patient deliveries with both frame-by-frame comparison and cumulative frame comparison. Simulated error case studies were used to demonstrate the system sensitivity and performance. The accuracy of the synchronization method was shown to agree within two control points which corresponds to approximately ∼1% of the total MU to be delivered for dynamic IMRT. The system achieved mean real-time gamma results for frame-by-frame analysis of 86.6% and 89.0% for 3%, 3 mm and 4%, 4 mm criteria, respectively, and 97.9% and 98.6% for cumulative gamma analysis. The system can detect a 10% MU error using 3%, 3 mm criteria within approximately 10 s. The EPID-based real-time delivery verification system successfully detected simulated gross errors introduced into patient plan deliveries in near real-time (within 0.1 s). A real-time radiation delivery verification system for dynamic IMRT has been demonstrated that is designed to prevent major mistreatments in modern radiation therapy.

Effects of feed delivery frequency in different environmental conditions on time budget of lactating dairy cows.

PubMed

Mattachini, Gabriele; Bava, Luciana; Sandrucci, Anna; Tamburini, Alberto; Riva, Elisabetta; Provolo, Giorgio

2017-08-01

This study aimed to examine the influence of feed delivery frequency and environmental conditions on daily time budget of lactating dairy cows. The study was carried out in two commercial dairy farms with Holstein herds. Fifty lactating dairy cows milked in automatic milking units (AMS farm) and 96 primiparous lactating dairy cows milked in a conventional milking parlour (conventional farm) were exposed to different frequencies of feed delivery replicated in different periods of the year (warm and mild) that were characterized by different temperature-humidity indices (THI). On each farm, feeding treatments consisted of two different feed delivery frequencies (1× and 2× on the AMS farm; 2× and 3× on the conventional farm). All behaviours of the cows were monitored for the last 8 d of each treatment period using continuous video recording. The two data sets from different farm systems were considered separately for analysis. On both farms, environmental conditions expressed as THI affected time budgets and the pattern of the behavioural indices throughout the day. The variation in the frequency of feed delivery seems to affect the cow's time budget only in a limited way. Standing time of cows on the conventional farm and the time spent by cows in the milking waiting area on the AMS farm both increased in response to increased feeding frequency. Although feed delivery frequency showed limited influence on cow's time budget, the effect on standing time could be carefully considered, especially on farms equipped with AMS where the type of cow traffic system (e.g., milking first) might amplify the negative consequences of more frequent feed delivery. Further investigations are required to evaluate the effect of THI and feed delivery frequency on other aspects of behavioural activity.

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.

Instrumental delivery of the fetal head at the time of elective repeat cesarean: a randomized pilot study.

PubMed

Bofill, J A; Lencki, S G; Barhan, S; Ezenagu, L C

2000-01-01

We sought to ascertain whether the routine use of instruments, forceps or vacuum, at the time of elective repeat cesarean delivery, permits a delivery that is as safe for mother and infant and as easy for mother and physician as traditional manual delivery of the fetal head. In this prospective study 44 women undergoing elective repeat cesarean were randomized to deliver by Vacuum (V), Forceps (F), or by Manual (M) means. Groups were compared with regard to demographic variables and maternal and neonatal outcomes. Deliveries were timed from entry into the uterus until full delivery of the infant. Maternal pain scores were assessed using a 10-cm visual analog scale. There were no differences in demographic variables except that the M group had fewer women with up to two cesareans. A large percentage of women in each group were delivered with the randomized instrument. Use of the V did not demonstrate fewer extensions of the uterine incision or lesser amounts of blood loss as measured by serial hemoglobin determinations. There was a trend for the F group to require a longer period of time for delivery (p = 0.061). Women in the V group reported significantly lower pain scores (p = 0.015). There were no serious neonatal injuries. The routine use of instruments at the time of elective repeat cesarean delivery appears safe and effective.

An operating system for future aerospace vehicle computer systems

NASA Technical Reports Server (NTRS)

Foudriat, E. C.; Berman, W. J.; Will, R. W.; Bynum, W. L.

1984-01-01

The requirements for future aerospace vehicle computer operating systems are examined in this paper. The computer architecture is assumed to be distributed with a local area network connecting the nodes. Each node is assumed to provide a specific functionality. The network provides for communication so that the overall tasks of the vehicle are accomplished. The O/S structure is based upon the concept of objects. The mechanisms for integrating node unique objects with node common objects in order to implement both the autonomy and the cooperation between nodes is developed. The requirements for time critical performance and reliability and recovery are discussed. Time critical performance impacts all parts of the distributed operating system; e.g., its structure, the functional design of its objects, the language structure, etc. Throughout the paper the tradeoffs - concurrency, language structure, object recovery, binding, file structure, communication protocol, programmer freedom, etc. - are considered to arrive at a feasible, maximum performance design. Reliability of the network system is considered. A parallel multipath bus structure is proposed for the control of delivery time for time critical messages. The architecture also supports immediate recovery for the time critical message system after a communication failure.

Caesarean delivery before 39 weeks associated with selecting an auspicious time for birth in Taiwan.

PubMed

Chu, Kuei-Hui; Lee, Yu-Hsiang; Tai, Chen-Jei; Lin, Yu-Hung; Huang, Chiu-Mieh; Chien, Li-Yin

2015-09-01

Caesarean delivery before 39 weeks of gestation increases the risk of morbidity among infants. Taiwan has one of the highest caesarean rates in the world, but little attention has been paid to this issue. This study aimed to describe the rate of caesarean delivery before 39 weeks gestation among women who did not have labour signs and had a non-emergency caesarean delivery in Taiwan and to examine whether the phenomenon was associated with the Chinese cultural practice of selecting an auspicious time for birth. We recruited women at 15-28 weeks of pregnancy at 5 hospitals in northern Taiwan and followed them at 4 or 5 weeks after delivery using structured questionnaires. This analysis included 150 primiparous mothers with a singleton pregnancy who had a non-emergency caesarean delivery without the presence of labour signs. Ninety-three of these women (62.0%) had caesarean deliveries before 39 weeks of gestation. Logistic regression analysis showed that women who had selected an auspicious time for delivery (OR=2.82, 95% CI: 1.15-6.95) and delivered in medical centres (OR=5.26, 95% CI: 2.25-12.26) were more likely to deliver before 39 weeks of gestation. Non-emergency caesarean delivery before 39 weeks of gestation was common among the study women, and was related to the Chinese cultural practice of selecting an auspicious time for birth. Further studies are needed to examine the risks and benefits associated with timing of caesarean delivery in Taiwan in order to generate a consensus among obstetricians and give pregnant women appropriate information. Copyright © 2015 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

Time trends in births and cesarean deliveries among women with disabilities.

PubMed

Horner-Johnson, Willi; Biel, Frances M; Darney, Blair G; Caughey, Aaron B

2017-07-01

Although it is likely that childbearing among women with disabilities is increasing, no empirical data have been published on changes over time in the numbers of women with disabilities giving birth. Further, while it is known that women with disabilities are at increased risk of cesarean delivery, temporal trends in cesarean deliveries among women with disabilities have not been examined. To assess time trends in births by any mode and in primary cesarean deliveries among women with physical, sensory, or intellectual/developmental disabilities. We conducted a retrospective cohort study using linked vital records and hospital discharge data from all deliveries in California, 2000-2010 (n = 4,605,061). We identified women with potential disabilities using ICD-9 codes. We used descriptive statistics and visualizations to examine time patterns. Logistic regression analyses assessed the association between disability and primary cesarean delivery, stratified by year. Among all women giving birth, the proportion with a disability increased from 0.27% in 2000 to 0.80% in 2010. Women with disabilities had significantly elevated odds of primary cesarean delivery in each year, but the magnitude of the odds ratio decreased over time from 2.60 (95% CI = 2.25 = 2.99) in 2000 to 1.66 (95% CI = 1.51-1.81) in 2010. Adequate clinician training is needed to address the perinatal care needs of the increasing numbers of women with disabilities giving birth. Continued efforts to understand cesarean delivery patterns and reasons for cesarean deliveries may help guide further reductions in proportions of cesarean deliveries among women with disabilities relative to women without disabilities. Copyright © 2017 Elsevier Inc. All rights reserved.

Solvent/non-solvent sintering: a novel route to create porous microsphere scaffolds for tissue regeneration.

PubMed

Brown, Justin L; Nair, Lakshmi S; Laurencin, Cato T

2008-08-01

Solvent/non-solvent sintering creates porous polymeric microsphere scaffolds suitable for tissue engineering purposes with control over the resulting porosity, average pore diameter, and mechanical properties. Five different biodegradable biocompatible polyphosphazenes exhibiting glass transition temperatures from -8 to 41 degrees C and poly (lactide-co-glycolide), (PLAGA) a degradable polymer used in a number of biomedical settings, were examined to study the versatility of the process and benchmark the process to heat sintering. Parameters such as: solvent/non-solvent sintering solution composition and submersion time effect the sintering process. PLAGA microsphere scaffolds fabricated with solvent/non-solvent sintering exhibited an interconnected porosity and pore size of 31.9% and 179.1 mum, respectively which was analogous to that of conventional heat sintered PLAGA microsphere scaffolds. Biodegradable polyphosphazene microsphere scaffolds exhibited a maximum interconnected porosity of 37.6% and a maximum compressive modulus of 94.3 MPa. Solvent/non-solvent sintering is an effective strategy for sintering polymeric microspheres, with a broad spectrum of glass transition temperatures, under ambient conditions making it an excellent fabrication route for developing tissue engineering scaffolds and drug delivery vehicles. (c) 2007 Wiley Periodicals, Inc.

Solvent/Non-Solvent Sintering: A Novel Route to Create Porous Microsphere Scaffolds For Tissue Regeneration

PubMed Central

Brown, Justin L.; Nair, Lakshmi S.; Laurencin, Cato T.

2009-01-01

Solvent/non-solvent sintering creates porous polymeric microsphere scaffolds suitable for tissue engineering purposes with control over the resulting porosity, average pore diameter and mechanical properties. Five different biodegradable biocompatible polyphosphazenes exhibiting glass transition temperatures from −8°C to 41oC and poly(lactide-co-glycolide), (PLAGA) a degradable polymer used in a number of biomedical settings, were examined to study the versatility of the process and benchmark the process to heat sintering. Parameters such as: solvent/non-solvent sintering solution composition and submersion time effect the sintering process. PLAGA microsphere scaffolds fabricated with solvent/non-solvent sintering exhibited an interconnected porosity and pore size of 31.9% and 179.1µm respectively which was analogous to that of conventional heat sintered PLAGA microsphere scaffolds. Biodegradable polyphosphazene microsphere scaffolds exhibited a maximum interconnected porosity of 37.6% and a maximum compressive modulus of 94.3MPa. Solvent/non-solvent sintering is an effective strategy for sintering polymeric microspheres, with a broad spectrum of glass transition temperatures, under ambient conditions making it an excellent fabrication route for developing tissue engineering scaffolds and drug delivery vehicles. PMID:18161819

Providing a diet containing only maintenance levels of energy and protein during the latter stages of pregnancy resulted in a prolonged delivery time during parturition in rats.

PubMed

Tanaka, Y; Kadokawa, H

2012-01-01

In mammals, a prolonged delivery time during parturition is dangerous for both mother and fetus, although the mechanisms that prolong delivery are unclear. To investigate whether nutrition affects delivery time, we administered two feeds containing maintenance (L-feed) or higher (H-feed) levels of energy and protein at different points during the latter half of pregnancy and compared the effects of the various treatments on delivery time in rats. After the rats had been maintained on the L-feed and then copulated on pro-oestrus (Day 0), pregnant females were randomly allocated to one of three groups: (1) the no-improvement group, which was fed L-feed throughout gestation; (2) the early group, which was fed L-feed until Day 11 of gestation and then switched to H-feed; and (3) the late group, which was fed L-feed until Day 16 of gestation and then switched to H-feed. There was no significant difference in the number of pups among the three groups. However, delivery time was significantly longer in the no-improvement group (73.7±5.2 min) than the early (46.9±5.6 min) and late (55.4±5.5 min) groups. Consuming a maintenance diet during the latter half of pregnancy resulted in a prolonged delivery time.

Synthesis and characterization of drug loaded albumin mesospheres for intratumoral chemotherapy

NASA Astrophysics Data System (ADS)

Freeman, Shema Taian

Conventional chemotherapy is problematic due to toxic complications. Intratumoral (IT) drug delivery, offers a new, less toxic, potentially more effective treatment concept. The objectives of this research encompassed (1) an investigation of the synthesis of BSA mesospheres (MS) employing genipin (GEN) as a novel crosslinking agent, (2) comparison with glutaraldehyde (GTA) crosslinked mesosphere, (3) a study of process parameters to define conditions for the synthesis of 1-10microm drug loaded mesospheres, and (4) investigation of the drug delivery properties of such mesospheres for IT chemotherapy. Smooth, spherical BSA-MS, crosslinked with glutaraldehyde and genipin, were prepared in a dry particle size range of 1microm to 10microm. It was shown that increasing dispersion stirring rate, crosslinking time and GEN/BSA ratio led to a decrease in particle size and a narrower particle distribution. It was also shown that increasing crosslinking time, GEN/BSA ratio, BSA concentrations, GEN concentration slowed enzymatic degradation. Post-loading and in situ drug loading methods were studied for the incorporation of cyclophosphamide and cisplatin into mesospheres. Maximum post loading of cisplatin was 3.2% (w/w) and 2.6% (w/w) with GEN and with GTA crosslinking. For cyclophosphamide 8.2% (w/w) and 7.1% (w/w) loading was achieved with GEN and GTA respectively. In situ drug loaded MS genipin and glutaraldehyde crosslinked mesospheres were also synthesized with 1.8% (w/w) cisplatin (using GEN) and 1.2% (w/w) (using GTA). Maximum loading of 13.3% (w/w) was achieved for cyclophosphamide in genipin crosslinked mesospheres. The cytotoxicity of in situ loaded genipin and glutaraldehyde crosslinked cisplatin mesospheres was evaluated using a murine Lewis lung model. Both genipin and glutaraldehyde crosslinked BSA-cisplatin mesospheres proved to be cytotoxic during a 48 hour test. Ultimately a standard set of processing parameters (BSA concentration, CAB concentration, GEN concentration, GEN/BSA ratio, stabilization stirring rate and crosslinking time) were defined to produce both GEN and GTA crosslinked cisplatin and cyclophosphamide BSA mesospheres. In vitro analysis confirmed the utility of mesosphere bound drug. In several related studies, (1) IT delivered dispersions of mitoxantrone loaded albumin microspheres were shown to afford an effective treatment, with significantly prolonging animal survival and (2) genipin and gadolinium crosslinked MS were prepared from HA and BSA/HA.

Nanosuspension for the delivery of a poorly soluble anti-cancer kinase inhibitor.

PubMed

Danhier, Fabienne; Ucakar, Bernard; Vanderhaegen, Marie-Lyse; Brewster, Marcus E; Arien, Tina; Préat, Véronique

2014-09-01

We hypothesized that nanosuspensions could be promising for the delivery of the poorly water soluble anti-cancer multi-targeted kinase inhibitor, MTKi-327. Hence, the aims of this work were (i) to evaluate the MTKi-327 nanosuspension for parenteral and oral administrations and (ii) to compare this nanosuspension with other nanocarriers in terms of anti-cancer efficacy and pharmacokinetics. Therefore, four formulations of MTKi-327 were studied: (i) PEGylated PLGA-based nanoparticles, (ii) self-assembling PEG₇₅₀-p-(CL-co-TMC) polymeric micelles, (iii) nanosuspensions of MTKi-327; and (iv) Captisol solution (pH=3.5). All the nano-formulations presented a size below 200 nm. Injections of the highest possible dose of the three nano-formulations did not induce any side effects in mice. In contrast, the maximum tolerated dose of the control Captisol solution was 20-fold lower than its highest possible dose. The highest regrowth delay of A-431-tumor-bearing nude mice was obtained with MTKi-327 nanosuspension, administered intravenously, at a dose of 650 mg/kg. After intravenous and oral administration, the AUC₀₋∞ of MTKi-327 nanosuspension was 2.4-fold greater than that of the Captisol solution. Nanosuspension may be considered as an effective anti-cancer MTKi-327 delivery method due to (i) the higher MTKi-327 maximum tolerated dose, (ii) the possible intravenous injection of MTKi-327, (iii) its ability to enhance the administered dose and (iv) its higher efficacy. Copyright © 2014 Elsevier B.V. All rights reserved.

Quality assurance of dynamic parameters in volumetric modulated arc therapy

PubMed Central

Manikandan, A; Sarkar, B; Holla, R; Vivek, T R; Sujatha, N

2012-01-01

Objectives The purpose of this study was to demonstrate quality assurance checks for accuracy of gantry speed and position, dose rate and multileaf collimator (MLC) speed and position for a volumetric modulated arc treatment (VMAT) modality (Synergy® S; Elekta, Stockholm, Sweden), and to check that all the necessary variables and parameters were synchronous. Methods Three tests (for gantry position–dose delivery synchronisation, gantry speed–dose delivery synchronisation and MLC leaf speed and positions) were performed. Results The average error in gantry position was 0.5° and the average difference was 3 MU for a linear and a parabolic relationship between gantry position and delivered dose. In the third part of this test (sawtooth variation), the maximum difference was 9.3 MU, with a gantry position difference of 1.2°. In the sweeping field method test, a linear relationship was observed between recorded doses and distance from the central axis, as expected. In the open field method, errors were encountered at the beginning and at the end of the delivery arc, termed the “beginning” and “end” errors. For MLC position verification, the maximum error was −2.46 mm and the mean error was 0.0153 ±0.4668 mm, and 3.4% of leaves analysed showed errors of >±1 mm. Conclusion This experiment demonstrates that the variables and parameters of the Synergy® S are synchronous and that the system is suitable for delivering VMAT using a dynamic MLC. PMID:22745206

A novel software and conceptual design of the hardware platform for intensity modulated radiation therapy

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

Nguyen, Dan; Ruan, Dan; O’Connor, Daniel

Purpose: To deliver high quality intensity modulated radiotherapy (IMRT) using a novel generalized sparse orthogonal collimators (SOCs), the authors introduce a novel direct aperture optimization (DAO) approach based on discrete rectangular representation. Methods: A total of seven patients—two glioblastoma multiforme, three head & neck (including one with three prescription doses), and two lung—were included. 20 noncoplanar beams were selected using a column generation and pricing optimization method. The SOC is a generalized conventional orthogonal collimators with N leaves in each collimator bank, where N = 1, 2, or 4. SOC degenerates to conventional jaws when N = 1. For SOC-basedmore » IMRT, rectangular aperture optimization (RAO) was performed to optimize the fluence maps using rectangular representation, producing fluence maps that can be directly converted into a set of deliverable rectangular apertures. In order to optimize the dose distribution and minimize the number of apertures used, the overall objective was formulated to incorporate an L2 penalty reflecting the difference between the prescription and the projected doses, and an L1 sparsity regularization term to encourage a low number of nonzero rectangular basis coefficients. The optimization problem was solved using the Chambolle–Pock algorithm, a first-order primal–dual algorithm. Performance of RAO was compared to conventional two-step IMRT optimization including fluence map optimization and direct stratification for multileaf collimator (MLC) segmentation (DMS) using the same number of segments. For the RAO plans, segment travel time for SOC delivery was evaluated for the N = 1, N = 2, and N = 4 SOC designs to characterize the improvement in delivery efficiency as a function of N. Results: Comparable PTV dose homogeneity and coverage were observed between the RAO and the DMS plans. The RAO plans were slightly superior to the DMS plans in sparing critical structures. On average, the maximum and mean critical organ doses were reduced by 1.94% and 1.44% of the prescription dose. The average number of delivery segments was 12.68 segments per beam for both the RAO and DMS plans. The N = 2 and N = 4 SOC designs were, on average, 1.56 and 1.80 times more efficient than the N = 1 SOC design to deliver. The mean aperture size produced by the RAO plans was 3.9 times larger than that of the DMS plans. Conclusions: The DAO and dose domain optimization approach enabled high quality IMRT plans using a low-complexity collimator setup. The dosimetric quality is comparable or slightly superior to conventional MLC-based IMRT plans using the same number of delivery segments. The SOC IMRT delivery efficiency can be significantly improved by increasing the leaf numbers, but the number is still significantly lower than the number of leaves in a typical MLC.« less

A novel software and conceptual design of the hardware platform for intensity modulated radiation therapy.

PubMed

Nguyen, Dan; Ruan, Dan; O'Connor, Daniel; Woods, Kaley; Low, Daniel A; Boucher, Salime; Sheng, Ke

2016-02-01

To deliver high quality intensity modulated radiotherapy (IMRT) using a novel generalized sparse orthogonal collimators (SOCs), the authors introduce a novel direct aperture optimization (DAO) approach based on discrete rectangular representation. A total of seven patients-two glioblastoma multiforme, three head & neck (including one with three prescription doses), and two lung-were included. 20 noncoplanar beams were selected using a column generation and pricing optimization method. The SOC is a generalized conventional orthogonal collimators with N leaves in each collimator bank, where N = 1, 2, or 4. SOC degenerates to conventional jaws when N = 1. For SOC-based IMRT, rectangular aperture optimization (RAO) was performed to optimize the fluence maps using rectangular representation, producing fluence maps that can be directly converted into a set of deliverable rectangular apertures. In order to optimize the dose distribution and minimize the number of apertures used, the overall objective was formulated to incorporate an L2 penalty reflecting the difference between the prescription and the projected doses, and an L1 sparsity regularization term to encourage a low number of nonzero rectangular basis coefficients. The optimization problem was solved using the Chambolle-Pock algorithm, a first-order primal-dual algorithm. Performance of RAO was compared to conventional two-step IMRT optimization including fluence map optimization and direct stratification for multileaf collimator (MLC) segmentation (DMS) using the same number of segments. For the RAO plans, segment travel time for SOC delivery was evaluated for the N = 1, N = 2, and N = 4 SOC designs to characterize the improvement in delivery efficiency as a function of N. Comparable PTV dose homogeneity and coverage were observed between the RAO and the DMS plans. The RAO plans were slightly superior to the DMS plans in sparing critical structures. On average, the maximum and mean critical organ doses were reduced by 1.94% and 1.44% of the prescription dose. The average number of delivery segments was 12.68 segments per beam for both the RAO and DMS plans. The N = 2 and N = 4 SOC designs were, on average, 1.56 and 1.80 times more efficient than the N = 1 SOC design to deliver. The mean aperture size produced by the RAO plans was 3.9 times larger than that of the DMS plans. The DAO and dose domain optimization approach enabled high quality IMRT plans using a low-complexity collimator setup. The dosimetric quality is comparable or slightly superior to conventional MLC-based IMRT plans using the same number of delivery segments. The SOC IMRT delivery efficiency can be significantly improved by increasing the leaf numbers, but the number is still significantly lower than the number of leaves in a typical MLC.

Introducing heterogeneous users and vehicles into models and algorithms for the dial-a-ride problem.

PubMed

Parragh, Sophie N

2011-08-01

Dial-a-ride problems deal with the transportation of people between pickup and delivery locations. Given the fact that people are subject to transportation, constraints related to quality of service are usually present, such as time windows and maximum user ride time limits. In many real world applications, different types of users exist. In the field of patient and disabled people transportation, up to four different transportation modes can be distinguished. In this article we consider staff seats, patient seats, stretchers and wheelchair places. Furthermore, most companies involved in the transportation of the disabled or ill dispose of different types of vehicles. We introduce both aspects into state-of-the-art formulations and branch-and-cut algorithms for the standard dial-a-ride problem. Also a recent metaheuristic method is adapted to this new problem. In addition, a further service quality related issue is analyzed: vehicle waiting time with passengers aboard. Instances with up to 40 requests are solved to optimality. High quality solutions are obtained with the heuristic method.

Jetting of a ultrasound contrast microbubble near a rigid wall

NASA Astrophysics Data System (ADS)

Sarkar, Kausik; Mobadersany, Nima

2017-11-01

Micron sized gas-bubbles coated with a stabilizing shell of lipids or proteins, are used as contrast enhancing agents for ultrasound imaging. However, they are increasingly being explored for novel applications in drug delivery through a process called sonoporation, the reversible permeabilization of the cell membrane. Under sufficiently strong acoustic excitations, bubbles form a jet and collapse near a wall. The jetting of free bubbles has been extensively studied by boundary element method (BEM). Here, for the first time, we implemented a rigorous interfacial rheological model of the shell into BEM and investigated the jet formation. The code has been carefully validated against past results. Increasing shell elasticity decreases the maximum bubble volume and the collapse time, while the jet velocity increases. The shear stress on the wall is computed and analyzed. A phase diagram as functions of excitation pressure and wall separation describes jet formation. Effects of shell elasticity and frequency on the phase diagram are investigated. Partially supported by National Science Foundation.

Expiratory and phonation times as measures of disease severity in patients with Multiple Sclerosis. A case-control study.

PubMed

Nordio, Sara; Bernitsas, Evanthia; Meneghello, Francesca; Palmer, Katie; Stabile, Maria Rosaria; Dipietro, Laura; Di Stadio, Arianna

2018-04-21

Speech disorders are common in patients with Multiple Sclerosis (MS). They can be assessed with several methods, which are however expensive, complex, and not easily accessible to physicians during routine clinic visits. This study aimed at measuring maximum phonation times, maximum expiratory times, and articulation abilities scores in patients with MS compared to healthy subjects and at investigating if any of these parameters could be used as a measure of MS progression. 50 MS patients and 50 gender- and age-matched healthy controls were enrolled in the study. Maximum expiratory times and maximum phonation times were collected from both groups. Articulation abilities were evaluated using the articulation subtest from the Fussi assessment (dysarthria scores). MS patients were evaluated with the Expanded Disability Status Scale (EDSS). Correlations between EDSS scores and maximum expiratory times, maximum phonation times, and dysarthria scores were calculated. EDSS scores of MS patients ranged from 4.5 to 7.5. In MS patients, maximum expiratory times, maximum phonation times, and dysarthria scores were significantly altered compared to healthy controls. Moreover, the EDSS scores were correlated with the maximum expiratory times; the maximum expiratory times were correlated with the maximum phonation times, and the maximum phonation times were correlated with the dysarthria scores. As the expiratory times were significantly correlated with the EDSS scores, they could be used to measure the severity of MS and to monitor its progression. Copyright © 2018 Elsevier B.V. All rights reserved.

A procedure for rapid issue of red cells for emergency use.

PubMed

Weiskopf, Richard B; Webb, Mary; Stangle, Deena; Klinbergs, Gunter; Toy, Pearl

2005-04-01

A College of American Pathologists Q-Probe revealed that the median turnaround times for emergency requests for red blood cells from the operating room were 30 minutes to release of cells from the blood bank and 34 minutes to delivery to the operating room. These times may not be adequate to permit the red cells to provide sufficiently rapid delivery of oxygen in massively bleeding patients. To improve the time from emergency request for red cells to delivery to the operating room. A new emergency issue program was implemented for only the operating rooms; emergency issue to all other hospital locations remained unchanged. Six units of group O Rh-negative red blood cells (RBCs) are maintained in the blood bank in a separate basket with transfusion forms containing the unit numbers and expiration dates and a bag with one blood tubing segment from each unit. The times to issue and to delivery to the operating room suite were compared with time to issue of 2 group O Rh-negative RBCs for other hospital locations using the older system during the same time period and with the time to issue of 2 units to all other hospital locations during the preceding 2 years. A university hospital. Time between emergency request for red cells and delivery to the operating room. The time between blood bank notification and arrival in the operating room of the 6 units of RBCs was significantly shorter than the time required to just issue (not including delivery time) 2 units of RBCs to other hospital locations. With the new procedure, 82% of units issued reached the operating room within 2 minutes of request, 91% arrived within 3 minutes, and 100% arrived within 4 minutes. These percentages are significantly higher than those for only issue of blood (without delivery) using the older issuing procedure for all hospital locations during the previous 2 years (37%, 49%, and 66%, respectively; P = .007, .009, and .02, respectively) and for other locations during the same 7-month period (29%, 46%, and 73%, respectively; P = .004, .01, and .09, respectively). Time (mean [95% confidence interval]) from blood bank notification to delivery of RBCs to the operating room suite (2.1 [1.6-2.6] minutes, of which approximately 50-60 seconds is attributable to delivery time) was less than issue times (not including delivery times) using the older issuing procedure for other hospital locations during the same period (4.1 [3.1-5.0] minutes; P = .007). An emergency issue procedure can be used to issue several units of RBCs within 1 minute and have them delivered to the operating room within 2 minutes while maintaining sufficient controls and providing required information to satisfy patient and blood bank requirements.

Characterization of Chlorhexidine-Loaded Calcium-Hydroxide Microparticles as a Potential Dental Pulp-Capping Material.

PubMed

Priyadarshini, Balasankar M; Selvan, Subramanian T; Narayanan, Karthikeyan; Fawzy, Amr S

2017-06-22

This study explores the delivery of novel calcium hydroxide [Ca(OH)₂] microparticles loaded with chlorhexidine (CHX) for potential dental therapeutic and preventive applications. Herein, we introduce a new approach for drug-delivery to deep dentin-surfaces in the form of drug-loaded microparticles. Unloaded Ca(OH)₂ [Ca(OH)₂/Blank] and CHX-loaded/Ca(OH)₂ microparticles were fabricated by aqueous chemical-precipitation technique. The synthesized-microparticles were characterized in vitro for determination of surface-morphology, crystalline-features and thermal-properties examined by energy-dispersive X-ray scanning and transmission electron-microscopy (EDX-SEM/TEM), Fourier-transform infrared-spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA) and differential scanning-calorimetry (DSC). Time-related pH changes, initial antibacterial/biofilm-abilities and cytotoxicity of CHX-loaded/Ca(OH)₂ microparticles were evaluated. Microparticles were delivered to dentin-surfaces with subsequent SEM examination of treated dentin-substrates. The in vitro and ex vivo CHX-release profiles were characterized. Ca(OH)₂/Blank were hexagonal-shaped with highest z -average diameter whereas CHX-inclusion evidenced micro-metric spheres with distinguishable surface "rounded deposits" and a negative-shift in diameter. CHX:Ca(OH)₂/50 mg exhibited maximum encapsulation-efficiency with good antibacterial and cytocompatible properties. SEM examination revealed an intact layer of microparticles on exposed dentin-surfaces with retention of spherical shape and smooth texture. Microparticles loaded on dentin-surfaces showed prolonged release of CHX indicating substantial retention on dentin-substrates. This study validated the inherent-applicability of this novel drug-delivery approach to dentin-surfaces using micro-metric CHX-loaded/Ca(OH)₂ microparticles.

SU-E-T-784: Using MLC Log Files for Daily IMRT Delivery Verification

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

Stathakis, S; Defoor, D; Linden, P

2015-06-15

Purpose: To verify daily intensity modulated radiation therapy (IMRT) treatments using multi-leaf collimator (MLC) log files. Methods: The MLC log files from a NovalisTX Varian linear accelerator were used in this study. The MLC files were recorded daily for all patients undergoing IMRT or volumetric modulated arc therapy (VMAT). The first record of each patient was used as reference and all records for subsequent days were compared against the reference. An in house MATLAB software code was used for the comparisons. Each MLC log file was converted to a fluence map (FM) and a gamma index (γ) analysis was usedmore » for the evaluation of each daily delivery for every patient. The tolerance for the gamma index was set to 2% dose difference and 2mm distance to agreement while points with signal of 10% or lower of the maximum value were excluded from the comparisons. Results: The γ between each of the reference FMs and the consecutive daily fraction FMs had an average value of 99.1% (ranged from 98.2 to 100.0%). The FM images were reconstructed at various resolutions in order to study the effect of the resolution on the γ and at the same time reduce the time for processing the images. We found that the comparison of images with the highest resolution (768×1024) yielded on average a lower γ (99.1%) than the ones with low resolution (192×256) (γ 99.5%). Conclusion: We developed an in-house software that allows us to monitor the quality of daily IMRT and VMAT treatment deliveries using information from the MLC log files of the linear accelerator. The information can be analyzed and evaluated as early as after the completion of each daily treatment. Such tool can be valuable to assess the effect of MLC positioning on plan quality, especially in the context of adaptive radiotherapy.« less

TH-E-BRE-04: An Online Replanning Algorithm for VMAT

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

Ahunbay, E; Li, X; Moreau, M

2014-06-15

Purpose: To develop a fast replanning algorithm based on segment aperture morphing (SAM) for online replanning of volumetric modulated arc therapy (VMAT) with flattening filtered (FF) and flattening filter free (FFF) beams. Methods: A software tool was developed to interface with a VMAT planning system ((Monaco, Elekta), enabling the output of detailed beam/machine parameters of original VMAT plans generated based on planning CTs for FF or FFF beams. A SAM algorithm, previously developed for fixed-beam IMRT, was modified to allow the algorithm to correct for interfractional variations (e.g., setup error, organ motion and deformation) by morphing apertures based on themore » geometric relationship between the beam's eye view of the anatomy from the planning CT and that from the daily CT for each control point. The algorithm was tested using daily CTs acquired using an in-room CT during daily IGRT for representative prostate cancer cases along with their planning CTs. The algorithm allows for restricted MLC leaf travel distance between control points of the VMAT delivery to prevent SAM from increasing leaf travel, and therefore treatment delivery time. Results: The VMAT plans adapted to the daily CT by SAM were found to improve the dosimetry relative to the IGRT repositioning plans for both FF and FFF beams. For the adaptive plans, the changes in leaf travel distance between control points were < 1cm for 80% of the control points with no restriction. When restricted to the original plans' maximum travel distance, the dosimetric effect was minimal. The adaptive plans were delivered successfully with similar delivery times as the original plans. The execution of the SAM algorithm was < 10 seconds. Conclusion: The SAM algorithm can quickly generate deliverable online-adaptive VMAT plans based on the anatomy of the day for both FF and FFF beams.« less

7 CFR 82.6 - Rate of payment; total payments.

Code of Federal Regulations, 2011 CFR

2011-01-01

... actual 2005 deliveries of clingstone peaches to processors from those acres of clingstone peach trees... minimum of $500 per acre and a maximum of $1,700 per acre. (b) Payment under paragraph (a) of this section will only be made after tree removal has been verified by the staff of the CCPA. (c) The $100 per ton...

7 CFR 82.6 - Rate of payment; total payments.

Code of Federal Regulations, 2014 CFR

2014-01-01

... actual 2005 deliveries of clingstone peaches to processors from those acres of clingstone peach trees... minimum of $500 per acre and a maximum of $1,700 per acre. (b) Payment under paragraph (a) of this section will only be made after tree removal has been verified by the staff of the CCPA. (c) The $100 per ton...

7 CFR 82.6 - Rate of payment; total payments.

Code of Federal Regulations, 2012 CFR

2012-01-01

... actual 2005 deliveries of clingstone peaches to processors from those acres of clingstone peach trees... minimum of $500 per acre and a maximum of $1,700 per acre. (b) Payment under paragraph (a) of this section will only be made after tree removal has been verified by the staff of the CCPA. (c) The $100 per ton...

7 CFR 82.6 - Rate of payment; total payments.

Code of Federal Regulations, 2013 CFR

2013-01-01

... actual 2005 deliveries of clingstone peaches to processors from those acres of clingstone peach trees... minimum of $500 per acre and a maximum of $1,700 per acre. (b) Payment under paragraph (a) of this section will only be made after tree removal has been verified by the staff of the CCPA. (c) The $100 per ton...

7 CFR 46.44 - Good delivery.

Code of Federal Regulations, 2010 CFR

2010-01-01

...) Lettuce. (1) If the contract specifies a U.S. grade, the lettuce may contain an average of not more than 3... U.S. Standards for Grades of Lettuce. (For example, the U.S. No. 1 grade provides a 12 percent... lettuce at destination may contain a maximum of 15 percent, by count, of the heads in any lot which are...

SU-E-T-610: Comparison of Treatment Times Between the MLCi and Agility Multileaf Collimators

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

Ramsey, C; Bowling, J

2014-06-01

Purpose: The Agility is a new 160-leaf MLC developed by Elekta for use in their Infinity and Versa HD linacs. As compared to the MLCi, the Agility increased the maximum leaf speed from 2 cm/s to 3.5 cm/s, and the maximum primary collimator speed from 1.5 cm/s to 9.0 cm/s. The purpose of this study was to determine if the Agility MLC resulted in improved plan quality and/or shorter treatment times. Methods: An Elekta Infinity that was originally equipped with a 80 leaf MLCi was upgraded to an 160 leaf Agility. Treatment plan quality was evaluated using the Pinnacle planningmore » system with SmartArc. Optimization was performed once for the MLCi and once for the Agility beam models using the same optimization parameters and the same number of iterations. Patient treatment times were measured for all IMRT, VMAT, and SBRT patients treated on the Infinity with the MLCi and Agility MLCs. Treatment times were extracted from the EMR and measured from when the patient first walked into the treatment room until exiting the treatment room. Results: 11,380 delivery times were measured for patients treated with the MLCi, and 1,827 measurements have been made for the Agility MLC. The average treatment times were 19.1 minutes for the MLCi and 20.8 minutes for the Agility. Using a t-test analysis, there was no difference between the two groups (t = 0.22). The dose differences between patients planned with the MLCi and the Agility MLC were minimal. For example, the dose difference for the PTV, GTV, and cord for a head and neck patient planned using Pinnacle were effectively equivalent. However, the dose to the parotid glands was slightly worse with the Agility MLC. Conclusion: There was no statistical difference in treatment time, or any significant dosimetric difference between the Agility MLC and the MLCi.« less

The effects of variable-time versus contingent reinforcement delivery on problem behavior maintained by escape.

PubMed

Lomas Mevers, Joanna E; Fisher, Wayne W; Kelley, Michael E; Fredrick, Laura D

2014-01-01

Results of previous research indicate that the delivery of positive reinforcement (e.g., food) for an appropriate, alternative target response (e.g., compliance) or delivery of food on a time-based schedule can decrease problem behavior reinforced by escape, even when problem behavior continues to produce negative reinforcement (e.g., Lalli et al., ; Lomas, Fisher, & Kelley, ). In this study, we compared the levels of both compliance and problem behavior when food and praise were delivered either contingent on compliance or on a time-based schedule. Results for 3 of the 4 participants showed that contingent delivery of preferred edible items and praise was more effective in both reducing problem behavior and increasing compliance compared to variable-time delivery of these same items. These findings are discussed in the context of motivating operations and competition between positive and negative reinforcement. © Society for the Experimental Analysis of Behavior.

Treatment planning, optimization, and beam delivery technqiues for intensity modulated proton therapy

NASA Astrophysics Data System (ADS)

Sengbusch, Evan R.

Physical properties of proton interactions in matter give them a theoretical advantage over photons in radiation therapy for cancer treatment, but they are seldom used relative to photons. The primary barriers to wider acceptance of proton therapy are the technical feasibility, size, and price of proton therapy systems. Several aspects of the proton therapy landscape are investigated, and new techniques for treatment planning, optimization, and beam delivery are presented. The results of these investigations suggest a means by which proton therapy can be delivered more efficiently, effectively, and to a much larger proportion of eligible patients. An analysis of the existing proton therapy market was performed. Personal interviews with over 30 radiation oncology leaders were conducted with regard to the current and future use of proton therapy. In addition, global proton therapy market projections are presented. The results of these investigations serve as motivation and guidance for the subsequent development of treatment system designs and treatment planning, optimization, and beam delivery methods. A major factor impacting the size and cost of proton treatment systems is the maximum energy of the accelerator. Historically, 250 MeV has been the accepted value, but there is minimal quantitative evidence in the literature that supports this standard. A retrospective study of 100 patients is presented that quantifies the maximum proton kinetic energy requirements for cancer treatment, and the impact of those results with regard to treatment system size, cost, and neutron production is discussed. This study is subsequently expanded to include 100 cranial stereotactic radiosurgery (SRS) patients, and the results are discussed in the context of a proposed dedicated proton SRS treatment system. Finally, novel proton therapy optimization and delivery techniques are presented. Algorithms are developed that optimize treatment plans over beam angle, spot size, spot spacing, beamlet weight, the number of delivered beamlets, and the number of delivery angles. These methods are evaluated via treatment planning studies including left-sided whole breast irradiation, lung stereotactic body radiotherapy, nasopharyngeal carcinoma, and whole brain radiotherapy with hippocampal avoidance. Improvements in efficiency and efficacy relative to traditional proton therapy and intensity modulated photon radiation therapy are discussed.

Labor Patterns in Women Attempting Vaginal Birth After Cesarean With Normal Neonatal Outcomes

PubMed Central

GRANTZ, Katherine L.; GONZALEZ-QUINTERO, Victor; TROENDLE, James; REDDY, Uma M.; HINKLE, Stefanie N.; KOMINIAREK, Michelle A.; LU, Zhaohui; ZHANG, Jun

2015-01-01

Objective To describe labor patterns in women with a trial of labor after cesarean (TOLAC) with normal neonatal outcomes. Study Design In a retrospective observational study at 12 U.S. centers (2002–2008), we examined time interval for each centimeter of cervical dilation and compared labor progression stratified by spontaneous or induced labor in 2,892 multiparous women with TOLAC (second delivery) and 56,301 nulliparous women at 37 0/7 to 41 6/7 weeks of gestation. Analyses were performed including women with intrapartum cesarean delivery, and then repeated limiting only to women who delivered vaginally. Results Labor was induced in 23.4% of TOLAC and 44.1% of nulliparous women (P<.001). Cesarean delivery rates were 57.7% in TOLAC versus 19.0% in nulliparous women (P<.001). Oxytocin was used in 52.4% of TOLAC versus 64.3% of nulliparous women with spontaneous labor (P<.001) and 89.8% of TOLAC versus 91.6% of nulliparous women with induced labor (P=.099); however, TOLAC had lower maximum doses of oxytocin compared to nulliparous women: median (90th percentile): 6 (18) mU/min versus 12 (28) mU/min, respectively (P<.001). Median (95th percentile) labor duration for TOLAC versus nulliparous women with spontaneous labor from 4–10cm was 0.9 (2.2) hours longer (P=.007). For women who entered labor spontaneously and achieved vaginal delivery, labor patterns for TOLAC were similar to nulliparous women. For induced labor, labor duration for TOLAC versus nulliparous women from 4–10cm was 1.5 (4.6) hours longer (P<.001). For women who achieved vaginal delivery, labor patterns were slower for induced TOLAC compared to nulliparous women. Conclusions Labor duration for TOLAC was slower compared to nulliparous labor, particularly for induced labor. By improved understanding of the rates of progress at different points in labor, this new information on labor curves in women undergoing TOLAC, particularly for induction, should help physicians when managing labor. PMID:25935774

Quality control procedures for dynamic treatment delivery techniques involving couch motion.

PubMed

Yu, Victoria Y; Fahimian, Benjamin P; Xing, Lei; Hristov, Dimitre H

2014-08-01

In this study, the authors introduce and demonstrate quality control procedures for evaluating the geometric and dosimetric fidelity of dynamic treatment delivery techniques involving treatment couch motion synchronous with gantry and multileaf collimator (MLC). Tests were designed to evaluate positional accuracy, velocity constancy and accuracy for dynamic couch motion under a realistic weight load. A test evaluating the geometric accuracy of the system in delivering treatments over complex dynamic trajectories was also devised. Custom XML scripts that control the Varian TrueBeam™ STx (Serial #3) axes in Developer Mode were written to implement the delivery sequences for the tests. Delivered dose patterns were captured with radiographic film or the electronic portal imaging device. The couch translational accuracy in dynamic treatment mode was 0.01 cm. Rotational accuracy was within 0.3°, with 0.04 cm displacement of the rotational axis. Dose intensity profiles capturing the velocity constancy and accuracy for translations and rotation exhibited standard deviation and maximum deviations below 3%. For complex delivery involving MLC and couch motions, the overall translational accuracy for reproducing programmed patterns was within 0.06 cm. The authors conclude that in Developer Mode, TrueBeam™ is capable of delivering dynamic treatment delivery techniques involving couch motion with good geometric and dosimetric fidelity.

Solid lipid nanoparticles as insulin inhalation carriers for enhanced pulmonary delivery.

PubMed

Bi, Ru; Shao, Wei; Wang, Qun; Zhang, Na

2009-02-01

Growing attentions have been paid to the pulmonary route for systemic delivery of peptide and protein drugs, such as insulin. Advantages of this non-injective route include rapid drug deposition in the target organ, fewer systemic side effects and avoiding first pass metabolism. However, sustained release formulations for pulmonary delivery have not been fully exploited till now. In our study, a novel dry powder inhalation (DPI) system of insulin loaded solid lipid nanoparticles (Ins-SLNs) was investigated for prolonged drug release, improved stability and effective inhalation. Firstly, the drug was incorporated into the lipid carriers for a maximum entrapment efficiency as high as 69.47 +/- 3.27% (n = 3). Secondly, DPI formulation was prepared by spray freeze drying of Ins-SLNs suspension, with optimized lyoprotectant and technique parameters in this procedure. The properties of DPI particles were characterized for their pulmonary delivery potency. Thirdly, the in vivo study of intratracheal instillation of Ins-SLNs to diabetic rats showed prolonged hypoglycemic effect and a relative pharmacological bioavailability of 44.40% could be achieved in the group of 8 IU/kg dosage. These results indicated that SLNs have shown increasing potential as an efficient and non-toxic lipophilic colloidal drug carrier for enhanced pulmonary delivery of insulin.

Shot sequencing based on biological equivalent dose considerations for multiple isocenter Gamma Knife radiosurgery

NASA Astrophysics Data System (ADS)

Ma, Lijun; Lee, Letitia; Barani, Igor; Hwang, Andrew; Fogh, Shannon; Nakamura, Jean; McDermott, Michael; Sneed, Penny; Larson, David A.; Sahgal, Arjun

2011-11-01

Rapid delivery of multiple shots or isocenters is one of the hallmarks of Gamma Knife radiosurgery. In this study, we investigated whether the temporal order of shots delivered with Gamma Knife Perfexion would significantly influence the biological equivalent dose for complex multi-isocenter treatments. Twenty single-target cases were selected for analysis. For each case, 3D dose matrices of individual shots were extracted and single-fraction equivalent uniform dose (sEUD) values were determined for all possible shot delivery sequences, corresponding to different patterns of temporal dose delivery within the target. We found significant variations in the sEUD values among these sequences exceeding 15% for certain cases. However, the sequences for the actual treatment delivery were found to agree (<3%) and to correlate (R2 = 0.98) excellently with the sequences yielding the maximum sEUD values for all studied cases. This result is applicable for both fast and slow growing tumors with α/β values of 2 to 20 according to the linear-quadratic model. In conclusion, despite large potential variations in different shot sequences for multi-isocenter Gamma Knife treatments, current clinical delivery sequences exhibited consistent biological target dosing that approached that maximally achievable for all studied cases.

Preclinical evaluation of convection-enhanced delivery of liposomal doxorubicin to treat pediatric diffuse intrinsic pontine glioma and thalamic high-grade glioma.

PubMed

Sewing, A Charlotte P; Lagerweij, Tonny; van Vuurden, Dannis G; Meel, Michaël H; Veringa, Susanna J E; Carcaboso, Angel M; Gaillard, Pieter J; Peter Vandertop, W; Wesseling, Pieter; Noske, David; Kaspers, Gertjan J L; Hulleman, Esther

2017-05-01

OBJECTIVE Pediatric high-grade gliomas (pHGGs) including diffuse intrinsic pontine gliomas (DIPGs) are primary brain tumors with high mortality and morbidity. Because of their poor brain penetrance, systemic chemotherapy regimens have failed to deliver satisfactory results; however, convection-enhanced delivery (CED) may be an alternative mode of drug delivery. Anthracyclines are potent chemotherapeutics that have been successfully delivered via CED in preclinical supratentorial glioma models. This study aims to assess the potency of anthracyclines against DIPG and pHGG cell lines in vitro and to evaluate the efficacy of CED with anthracyclines in orthotopic pontine and thalamic tumor models. METHODS The sensitivity of primary pHGG cell lines to a range of anthracyclines was tested in vitro. Preclinical CED of free doxorubicin and pegylated liposomal doxorubicin (PLD) to the brainstem and thalamus of naïve nude mice was performed. The maximum tolerated dose (MTD) was determined based on the observation of clinical symptoms, and brains were analyzed after H & E staining. Efficacy of the MTD was tested in adult glioma E98-FM-DIPG and E98-FM-thalamus models and in the HSJD-DIPG-007-Fluc primary DIPG model. RESULTS Both pHGG and DIPG cells were sensitive to anthracyclines in vitro. Doxorubicin was selected for further preclinical evaluation. Convection-enhanced delivery of the MTD of free doxorubicin and PLD in the pons was 0.02 mg/ml, and the dose tolerated in the thalamus was 10 times higher (0.2 mg/ml). Free doxorubicin or PLD via CED was ineffective against E98-FM-DIPG or HSJD-DIPG-007-Fluc in the brainstem; however, when applied in the thalamus, 0.2 mg/ml of PLD slowed down tumor growth and increased survival in a subset of animals with small tumors. CONCLUSIONS Local delivery of doxorubicin to the brainstem causes severe toxicity, even at doxorubicin concentrations that are safe in the thalamus. As a consequence, the authors could not establish a therapeutic window for treating orthotopic brainstem tumors in mice. For tumors in the thalamus, therapeutic concentrations to slow down tumor growth could be reached. These data suggest that anatomical location determines the severity of toxicity after local delivery of therapeutic agents and that caution should be used when translating data from supratentorial CED studies to treat infratentorial tumors.

Optoacoustic detection of thermal lesions

NASA Astrophysics Data System (ADS)

Arsenault, Michel G.; Kolios, Michael C.; Whelan, William M.

2009-02-01

Minimally invasive thermal therapy is being investigated as an alternative cancer treatment. It involves heating tissues to greater than 55°C over a period of a few minutes, which results in tissue coagulation. Optoacoustic (OA) imaging is a new imaging technique that involves exposing tissues to pulsed light and detecting the acoustic waves that are generated. In this study, adult bovine liver tissue samples were heated using continuous wave laser energy for various times, then scanned using an optoacoustic imaging system. Large optoacoustic signal variability was observed in the native tissue prior to heating. OA signal amplitude increased with maximum tissue temperature achieved, characterized by a correlation coefficient of 0.63. In this study we show that there are detectable changes in optoacoustic signal strength that arise from tissue coagulation, which demonstrates the potential of optoacoustic technology for the monitoring of thermal therapy delivery.

Development of a Video-Microscopic Tool To Evaluate the Precipitation Kinetics of Poorly Water Soluble Drugs: A Case Study with Tadalafil and HPMC.

PubMed

Christfort, Juliane Fjelrad; Plum, Jakob; Madsen, Cecilie Maria; Nielsen, Line Hagner; Sandau, Martin; Andersen, Klaus; Müllertz, Anette; Rades, Thomas

2017-12-04

Many drug candidates today have a low aqueous solubility and, hence, may show a low oral bioavailability, presenting a major formulation and drug delivery challenge. One way to increase the bioavailability of these drugs is to use a supersaturating drug delivery strategy. The aim of this study was to develop a video-microscopic method, to evaluate the effect of a precipitation inhibitor on supersaturated solutions of the poorly soluble drug tadalafil, using a novel video-microscopic small scale setup. Based on preliminary studies, a degree of supersaturation of 29 was chosen for the supersaturation studies with tadalafil in FaSSIF. Different amounts of hydroxypropyl methyl cellulose (HPMC) were predissolved in FaSSIF to give four different concentrations, and the supersaturated system was then created using a solvent shift method. Precipitation of tadalafil from the supersaturated solutions was monitored by video-microscopy as a function of time. Single-particle analysis was possible using commercially available software; however, to investigate the entire population of precipitating particles (i.e., their number and area covered in the field of view), an image analysis algorithm was developed (multiparticle analysis). The induction time for precipitation of tadalafil in FaSSIF was significantly prolonged by adding 0.01% (w/v) HPMC to FaSSIF, and the maximum inhibition was reached at 0.1% (w/v) HPMC, after which additional HPMC did not further increase the induction time. The single-particle and multiparticle analyses yielded the same ranking of the HPMC concentrations, regarding the inhibitory effect on precipitation. The developed small scale method to assess the effect of precipitation inhibitors can speed up the process of choosing the right precipitation inhibitor and the concentration to be used.

Pregnancy-associated obesity in black women in New York City.

PubMed

Lederman, Sally Ann; Alfasi, Goldie; Deckelbaum, Richard J

2002-03-01

To determine weight gain during pregnancy and weight changes postpartum in first-time mothers delivering at or near term. At about 2 weeks after delivery, 47 adult, Black and Hispanic women provided information on their prepregnancy weight and height and maximum pregnancy weight. Women reinterviewed at 2 and 6 months after delivery reported their most recent weight measurement and the date of that measurement. This information was used to compute each woman's prepregnancy body mass index, pregnancy weight gain, and weight loss postpartum. Information on infant feeding was also collected at each postpartum visit. About 2/3 of the women and 100% of the overweight and obese women gained excessive weight during pregnancy. Weight gain was most marked in women who started pregnancy overweight or obese. At 2 months postpartum, women were on average almost 18 lb above their prepregnancy weight. No additional maternal weight was lost by 6 months postpartum. Most infants were started on formula by 2 weeks of age. At 2 months of age, 85% were fed formula only and 91% of the infants were on WIC. Our results demonstrate a need for interventions to help women avoid obesity by regulating their pregnancy weight gain, losing weight for a longer period postpartum, and initiating and maintaining exclusive breast-feeding.

Oily nanosuspension for long-acting intramuscular delivery of curcumin didecanoate prodrug: preparation, characterization and in vivo evaluation.

PubMed

Wei, Xiao-Lan; Han, Ying-Rui; Quan, Li-Hui; Liu, Chun-Yu; Liao, Yong-Hong

2013-05-13

The objective of this study was to prepare the nanocrystals of curcumin didecanoate (CurDD) by wet ball milling and to investigate the comparative pharmacokinetics of oily nano- and micro-suspensions after intramuscular (i.m.) administration to rats. Upon optimizing the wet ball milling parameters, CurDD nanocrystals were produced with median particle size of ~500 nm and the freeze-dried nanocrystals were readily dispersed in peanut oil to form stable nanosuspensions. Although the nanosuspension appeared to exhibit slower clearance from the injection site after i.m. injection, compared to microsuspension (~5 μm), a significantly higher maximum plasma curcumin concentration (69.0 ng/ml) was observed for the former than that for the latter (18.5 ng/ml). In addition, the nanosuspension provided significant higher plasma curcumin concentrations and brain CurDD contents for at least 15 days than the microsuspension, except for the initial times. A single i.m. injection of nanosuspension appeared to achieve reversal effect on reserpine-induced hypothermia for at least 13 days. This study demonstrates that CurDD nanosuspension may act as a long-acting i.m. injectable for sustained delivery of curcumin, potentially applicable to elicit a long-lasting antidepressant effect. Copyright © 2013 Elsevier B.V. All rights reserved.

Fabrication of magnetite nano particles and modification with metal organic framework of Zn(2+) for sorption of doxycyline.

PubMed

Ghassemi Nooreini, Mahsa; Ahmad Panahi, Homayon

2016-10-15

This study presents a novel method for synthesis and characterization of a metal-organic framework and application in drug delivery. The first step was synthesis of amino functionalized magnetite that was then modified by a metal-organic framework of Zn(2+). This newly developed nano-sorbent was characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, energy dispersive x-ray spectroscopy, thermogravimetric analysis, vibrating sample magnetometer and x-ray diffraction. Doxycycline was loaded to the nano-sorbent and effects of the variable parameters, kinetics of adsorption, release and capacity of adsorption were investigated. Test results specified maximum sorption of 21.5mgg(-1) for doxycycline in conditions of nano-sorbent at pH 7 and optimum time of 10min. Equilibrium adsorption data were analyzed by the Langmuir, Freundlich and Temkin models. Results showed that about 40% of doxycycline was released in simulated gastric fluid for the 30min and more than 70% was released in simulated intestinal fluid during 12h. These results were satisfactory and demonstrate that this new nano-sorbent modified with metal-organic framework had a good level of efficiency for drug delivery of doxycycline. Copyright © 2016 Elsevier B.V. All rights reserved.

Nicotine Delivery and Vaping Behavior During ad Libitum E-cigarette Access.

PubMed

St Helen, Gideon; Ross, Kathryn C; Dempsey, Delia A; Havel, Christopher M; Jacob, Peyton; Benowitz, Neal L

2016-10-01

To characterize vaping behavior and nicotine intake during ad libitum e-cigarette access. Thirteen adult e-cigarette users had 90 minutes of videotaped ad libitum access to their usual e-cigarette. Plasma nicotine was measured before and every 15 minutes after the first puff; subjective effects were measured before and after the session. Average puff duration and interpuff interval were 3.5±1.4 seconds (±SD) and 118±141 seconds, respectively. 12% of puffs were unclustered puffs while 43%, 28%, and 17% were clustered in groups of 2-5, 6-10, and >10 puffs, respectively. On average, 4.0±3.3 mg of nicotine was inhaled; the maximum plasma nicotine concentration (C max ) was 12.8±8.5 ng/mL. Among the 8 tank users, number of puffs was positively correlated with amount of nicotine inhaled, C max , and area under the plasma nicotine concentration-time curve (AUC 0 → 90min ) while interpuff interval was negatively correlated with C max and AUC 0 → 90 . Vaping patterns differ from cigarette smoking. Plasma nicotine levels were consistent with intermittent dosing of nicotine from e-cigarettes compared to the more bolus dosing from cigarettes. Differences in delivery patterns and peak levels of nicotine achieved could influence the addictiveness of e-cigarettes compared to conventional cigarettes.

Streaming flow from ultrasound contrast agents by acoustic waves in a blood vessel model.

PubMed

Cho, Eunjin; Chung, Sang Kug; Rhee, Kyehan

2015-09-01

To elucidate the effects of streaming flow on ultrasound contrast agent (UCA)-assisted drug delivery, streaming velocity fields from sonicated UCA microbubbles were measured using particle image velocimetry (PIV) in a blood vessel model. At the beginning of ultrasound sonication, the UCA bubbles formed clusters and translated in the direction of the ultrasound field. Bubble cluster formation and translation were faster with 2.25MHz sonication, a frequency close to the resonance frequency of the UCA. Translation of bubble clusters induced streaming jet flow that impinged on the vessel wall, forming symmetric vortices. The maximum streaming velocity was about 60mm/s at 2.25MHz and decreased to 15mm/s at 1.0MHz for the same acoustic pressure amplitude. The effect of the ultrasound frequency on wall shear stress was more noticeable. Maximum wall shear stress decreased from 0.84 to 0.1Pa as the ultrasound frequency decreased from 2.25 to 1.0MHz. The maximum spatial gradient of the wall shear stress also decreased from 1.0 to 0.1Pa/mm. This study showed that streaming flow was induced by bubble cluster formation and translation and was stronger upon sonication by an acoustic wave with a frequency near the UCA resonance frequency. Therefore, the secondary radiant force, which is much stronger at the resonance frequency, should play an important role in UCA-assisted drug delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

Concentration dependence of biotransformation in fish liver S9: Optimizing substrate concentrations to estimate hepatic clearance for bioaccumulation assessment.

PubMed

Lo, Justin C; Allard, Gayatri N; Otton, S Victoria; Campbell, David A; Gobas, Frank A P C

2015-12-01

In vitro bioassays to estimate biotransformation rate constants of contaminants in fish are currently being investigated to improve bioaccumulation assessments of hydrophobic contaminants. The present study investigates the relationship between chemical substrate concentration and in vitro biotransformation rate of 4 environmental contaminants (9-methylanthracene, pyrene, chrysene, and benzo[a]pyrene) in rainbow trout (Oncorhynchus mykiss) liver S9 fractions and methods to determine maximum first-order biotransformation rate constants. Substrate depletion experiments using a series of initial substrate concentrations showed that in vitro biotransformation rates exhibit strong concentration dependence, consistent with a Michaelis-Menten kinetic model. The results indicate that depletion rate constants measured at initial substrate concentrations of 1 μM (a current convention) could underestimate the in vitro biotransformation potential and may cause bioconcentration factors to be overestimated if in vitro biotransformation rates are used to assess bioconcentration factors in fish. Depletion rate constants measured using thin-film sorbent dosing experiments were not statistically different from the maximum depletion rate constants derived using a series of solvent delivery-based depletion experiments for 3 of the 4 test chemicals. Multiple solvent delivery-based depletion experiments at a range of initial concentrations are recommended for determining the concentration dependence of in vitro biotransformation rates in fish liver fractions, whereas a single sorbent phase dosing experiment may be able to provide reasonable approximations of maximum depletion rates of very hydrophobic substances. © 2015 SETAC.

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.

Non-invasive magnetic resonance imaging follow-up of sono-sensitive liposome tumor delivery and controlled release after high-intensity focused ultrasound.

PubMed

Fowler, Robert Andrew; Fossheim, Sigrid L; Mestas, Jean-Louis; Ngo, Jacqueline; Canet-Soulas, Emmanuelle; Lafon, Cyril

2013-12-01

This work examines the use of lanthanide-based contrast agents and magnetic resonance imaging in monitoring liposomal behavior in vivo. Dysprosium (Dy) and gadolinium (Gd) chelates, Dy-diethylenetriaminepentaacetic acid bismethylamide (Dy-DTPA-BMA) and Gd-DTPA-BMA, were encapsulated in pegylated distearoylphosphatidylethanolamine-based (saturated) liposomes, and then intravenously injected into Copenhagen rats with subcutaneous Dunning AT2 xenografts. Liposome-encapsulated Dy chelate shortens transverse relaxation times (T(2) and T(2)*) of tissue; thus, liposomal accumulation in the tumor can be monitored by observing the decrease in T(2)* relaxation time over time. The tumor was treated at the time of maximum liposomal accumulation (48 h) with confocal, cavitating high-intensity focused ultrasound to induce liposomal payload release. Using liposome-encapsulated Gd chelate at high enough concentrations and saturated liposomal phospholipids induces an exchange-limited longitudinal (T(1)) relaxation when the liposomes are intact; when the liposomes are released, exchange limitation is relieved, thus allowing in vivo observation of payload release as a decrease in tumor T(1). Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

29 CFR 570.52 - Occupations of motor-vehicle driver and outside helper (Order 2).

Code of Federal Regulations, 2010 CFR

2010-07-01

... urgent, time-sensitive deliveries means trips which, because of such factors as customer satisfaction... for the purpose of delivering goods of the minor's employer to a customer (except urgent, time... delivery of pizzas and prepared foods to the customer; the delivery of materials under a deadline (such as...

75 FR 22725 - Express Mail Next Day Delivery Postage Refund Amendment

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-30

... at all times of deposit or between all Post Office TM facilities. Express Mail Second Day Delivery During the time period of December 22 through December 25, postage refunds for Express Mail Second Day..., or for which delivery to the addressee was not attempted on the second business day. These refunds...

Immunization Route Dictates Cross-Priming Efficiency and Impacts the Optimal Timing of Adjuvant Delivery

PubMed Central

Bouvier, Isabelle; Jusforgues-Saklani, Hélène; Lim, Annick; Lemaître, Fabrice; Lemercier, Brigitte; Auriau, Charlotte; Nicola, Marie-Anne; Leroy, Sandrine; Law, Helen K.; Bandeira, Antonio; Moon, James J.; Bousso, Philippe; Albert, Matthew L.

2011-01-01

Delivery of cell-associated antigen represents an important strategy for vaccination. While many experimental models have been developed in order to define the critical parameters for efficient cross-priming, few have utilized quantitative methods that permit the study of the endogenous repertoire. Comparing different strategies of immunization, we report that local delivery of cell-associated antigen results in delayed T cell cross-priming due to the increased time required for antigen capture and presentation. In comparison, delivery of disseminated antigen resulted in rapid T cell priming. Surprisingly, local injection of cell-associated antigen, while slower, resulted in the differentiation of a more robust, polyfunctional, effector response. We also evaluated the combination of cell-associated antigen with poly I:C delivery and observed an immunization route-specific effect regarding the optimal timing of innate immune stimulation. These studies highlight the importance of considering the timing and persistence of antigen presentation, and suggest that intradermal injection with delayed adjuvant delivery is the optimal strategy for achieving CD8+ T cell cross-priming. PMID:22566860

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 can be identified, reliable prediction of shoulder dystocia in this setting cannot be attained. Copyright © 2016 Elsevier Inc. All rights reserved.

SU-F-T-465: Two Years of Radiotherapy Treatments Analyzed Through MLC Log Files

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

Defoor, D; Kabat, C; Papanikolaou, N

Purpose: To present treatment statistics of a Varian Novalis Tx using more than 90,000 Varian Dynalog files collected over the past 2 years. Methods: Varian Dynalog files are recorded for every patient treated on our Varian Novalis Tx. The files are collected and analyzed daily to check interfraction agreement of treatment deliveries. This is accomplished by creating fluence maps from the data contained in the Dynalog files. From the Dynalog files we have also compiled statistics for treatment delivery times, MLC errors, gantry errors and collimator errors. Results: The mean treatment time for VMAT patients was 153 ± 86 secondsmore » while the mean treatment time for step & shoot was 256 ± 149 seconds. Patient’s treatment times showed a variation of 0.4% over there treatment course for VMAT and 0.5% for step & shoot. The average field sizes were 40 cm2 and 26 cm2 for VMAT and step & shoot respectively. VMAT beams contained and average overall leaf travel of 34.17 meters and step & shoot beams averaged less than half of that at 15.93 meters. When comparing planned and delivered fluence maps generated using the Dynalog files VMAT plans showed an average gamma passing percentage of 99.85 ± 0.47. Step & shoot plans showed an average gamma passing percentage of 97.04 ± 0.04. 5.3% of beams contained an MLC error greater than 1 mm and 2.4% had an error greater than 2mm. The mean gantry speed for VMAT plans was 1.01 degrees/s with a maximum of 6.5 degrees/s. Conclusion: Varian Dynalog files are useful for monitoring machine performance treatment parameters. The Dynalog files have shown that the performance of the Novalis Tx is consistent over the course of a patients treatment with only slight variations in patient treatment times and a low rate of MLC errors.« less

Osmotically driven drug delivery through remote-controlled magnetic nanocomposite membranes.

PubMed

Zaher, A; Li, S; Wolf, K T; Pirmoradi, F N; Yassine, O; Lin, L; Khashab, N M; Kosel, J

2015-09-01

Implantable drug delivery systems can provide long-term reliability, controllability, and biocompatibility, and have been used in many applications, including cancer pain and non-malignant pain treatment. However, many of the available systems are limited to zero-order, inconsistent, or single burst event drug release. To address these limitations, we demonstrate prototypes of a remotely operated drug delivery device that offers controllability of drug release profiles, using osmotic pumping as a pressure source and magnetically triggered membranes as switchable on-demand valves. The membranes are made of either ethyl cellulose, or the proposed stronger cellulose acetate polymer, mixed with thermosensitive poly(N-isopropylacrylamide) hydrogel and superparamagnetic iron oxide particles. The prototype devices' drug diffusion rates are on the order of 0.5-2 μg/h for higher release rate designs, and 12-40 ng/h for lower release rates, with maximum release ratios of 4.2 and 3.2, respectively. The devices exhibit increased drug delivery rates with higher osmotic pumping rates or with magnetically increased membrane porosity. Furthermore, by vapor deposition of a cyanoacrylate layer, a drastic reduction of the drug delivery rate from micrograms down to tens of nanograms per hour is achieved. By utilizing magnetic membranes as the valve-control mechanism, triggered remotely by means of induction heating, the demonstrated drug delivery devices benefit from having the power source external to the system, eliminating the need for a battery. These designs multiply the potential approaches towards increasing the on-demand controllability and customizability of drug delivery profiles in the expanding field of implantable drug delivery systems, with the future possibility of remotely controlling the pressure source.

Osmotically driven drug delivery through remote-controlled magnetic nanocomposite membranes

PubMed Central

Zaher, A.; Li, S.; Wolf, K. T.; Pirmoradi, F. N.; Yassine, O.; Lin, L.; Khashab, N. M.; Kosel, J.

2015-01-01

Implantable drug delivery systems can provide long-term reliability, controllability, and biocompatibility, and have been used in many applications, including cancer pain and non-malignant pain treatment. However, many of the available systems are limited to zero-order, inconsistent, or single burst event drug release. To address these limitations, we demonstrate prototypes of a remotely operated drug delivery device that offers controllability of drug release profiles, using osmotic pumping as a pressure source and magnetically triggered membranes as switchable on-demand valves. The membranes are made of either ethyl cellulose, or the proposed stronger cellulose acetate polymer, mixed with thermosensitive poly(N-isopropylacrylamide) hydrogel and superparamagnetic iron oxide particles. The prototype devices' drug diffusion rates are on the order of 0.5–2 μg/h for higher release rate designs, and 12–40 ng/h for lower release rates, with maximum release ratios of 4.2 and 3.2, respectively. The devices exhibit increased drug delivery rates with higher osmotic pumping rates or with magnetically increased membrane porosity. Furthermore, by vapor deposition of a cyanoacrylate layer, a drastic reduction of the drug delivery rate from micrograms down to tens of nanograms per hour is achieved. By utilizing magnetic membranes as the valve-control mechanism, triggered remotely by means of induction heating, the demonstrated drug delivery devices benefit from having the power source external to the system, eliminating the need for a battery. These designs multiply the potential approaches towards increasing the on-demand controllability and customizability of drug delivery profiles in the expanding field of implantable drug delivery systems, with the future possibility of remotely controlling the pressure source. PMID:26487899

TH-AB-202-02: Real-Time Verification and Error Detection for MLC Tracking Deliveries Using An Electronic Portal Imaging Device

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

J Zwan, B; Central Coast Cancer Centre, Gosford, NSW; Colvill, E

2016-06-15

Purpose: The added complexity of the real-time adaptive multi-leaf collimator (MLC) tracking increases the likelihood of undetected MLC delivery errors. In this work we develop and test a system for real-time delivery verification and error detection for MLC tracking radiotherapy using an electronic portal imaging device (EPID). Methods: The delivery verification system relies on acquisition and real-time analysis of transit EPID image frames acquired at 8.41 fps. In-house software was developed to extract the MLC positions from each image frame. Three comparison metrics were used to verify the MLC positions in real-time: (1) field size, (2) field location and, (3)more » field shape. The delivery verification system was tested for 8 VMAT MLC tracking deliveries (4 prostate and 4 lung) where real patient target motion was reproduced using a Hexamotion motion stage and a Calypso system. Sensitivity and detection delay was quantified for various types of MLC and system errors. Results: For both the prostate and lung test deliveries the MLC-defined field size was measured with an accuracy of 1.25 cm{sup 2} (1 SD). The field location was measured with an accuracy of 0.6 mm and 0.8 mm (1 SD) for lung and prostate respectively. Field location errors (i.e. tracking in wrong direction) with a magnitude of 3 mm were detected within 0.4 s of occurrence in the X direction and 0.8 s in the Y direction. Systematic MLC gap errors were detected as small as 3 mm. The method was not found to be sensitive to random MLC errors and individual MLC calibration errors up to 5 mm. Conclusion: EPID imaging may be used for independent real-time verification of MLC trajectories during MLC tracking deliveries. Thresholds have been determined for error detection and the system has been shown to be sensitive to a range of delivery errors.« less

Nano-Chitosan Particles in Anticancer Drug Delivery: An Up-to-Date Review.

PubMed

Kamath, Pooja R; Sunil, Dhanya

2017-01-01

Cancer is one of the most awful lethal diseases all over the world and the success of its current chemotherapeutic treatment strategies is limited due to several associated drawbacks. The exploration of cancer cell physiology and its microenvironment has exposed the potential of various classes of nanocarriers to deliver anticancer chemotherapeutic agents at the tumor target site. These nanocarriers must evade the immune surveillance system and achieve target selectivity. Besides, they must gain access into the interior of cancerous cells, evade endosomal entrapment and discharge the drugs in a sustained manner. Chitosan, the second naturally abundant polysaccharide is a biocompatible, biodegradable and mucoadhesive cationic polymer which has been exploited extensively in the last few years in the effective delivery of anticancer chemotherapeutics to the target tumor cells. Therapeutic agent-loaded surface modified chitosan nanoparticles are established to be more stable, permeable and bioactive. This review will provide an up-to-date evidence-based background on recent pharmaceutical advancements in the transformation of chitosan nanoparticles for smart anticancer therapeutic drug delivery. • Efforts to improve cancer chemotherapy by exploiting the intrinsic differences between normal and neoplastic cells to achieve maximum effective drug delivery to target cancer cells through bioengineered chitosan nano delivery vectors are discussed. • The easy manipulation of surface characteristics of chitosan based nanoparticles by various functionalization methods to achieve targeted drug delivery proves its potential to be an essential tool for the advancement of anticancer drug-delivery vectors. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

Dosimetric comparison of 3D conformal, IMRT, and V-MAT techniques for accelerated partial-breast irradiation (APBI)

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

Qiu, Jian-Jian; Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai

2014-07-01

The purpose is to dosimetrically compare the following 3 delivery techniques: 3-dimensional conformal radiation therapy (3D-CRT), intensity-modulated arc therapy (IMRT), and volumetric-modulated arc therapy (V-MAT) in the treatment of accelerated partial-breast irradiation (APBI). Overall, 16 patients with T1/2N0 breast cancer were treated with 3D-CRT (multiple, noncoplanar photon fields) on the RTOG 0413 partial-breast trial. These cases were subsequently replanned using static gantry IMRT and V-MAT technology to understand dosimetric differences among these 3 techniques. Several dosimetric parameters were used in plan quality evaluation, including dose conformity index (CI) and dose-volume histogram analysis of normal tissue coverage. Quality assurance studies includingmore » gamma analysis were performed to compare the measured and calculated dose distributions. The IMRT and V-MAT plans gave more conformal target dose distributions than the 3D-CRT plans (p < 0.05 in CI). The volume of ipsilateral breast receiving 5 and 10 Gy was significantly less using the V-MAT technique than with either 3D-CRT or IMRT (p < 0.05). The maximum lung dose and the ipsilateral lung volume receiving 10 (V{sub 10}) or 20 Gy (V{sub 20}) were significantly less with both V-MAT and IMRT (p < 0.05). The IMRT technique was superior to 3D-CRT and V-MAT of low dose distributions in ipsilateral lung (p < 0.05 in V{sub 5} and D{sub 5}). The total mean monitor units (MUs) for V-MAT (621.0 ± 111.9) were 12.2% less than those for 3D-CRT (707.3 ± 130.9) and 46.5% less than those for IMRT (1161.4 ± 315.6) (p < 0.05). The average machine delivery time was 1.5 ± 0.2 minutes for the V-MAT plans, 7.0 ± 1.6 minutes for the 3D-CRT plans, and 11.5 ± 1.9 minutes for the IMRT plans, demonstrating much less delivery time for V-MAT. Based on this preliminary study, V-MAT and IMRT techniques offer improved dose conformity as compared with 3D-CRT techniques without increasing dose to the ipsilateral lung. In terms of MU and delivery time, V-MAT is significantly more efficient for APBI than for conventional 3D-CRT and static-beam IMRT.« less

Monitoring and Modeling Performance of Communications in Computational Grids

NASA Technical Reports Server (NTRS)

Frumkin, Michael A.; Le, Thuy T.

2003-01-01

Computational grids may include many machines located in a number of sites. For efficient use of the grid we need to have an ability to estimate the time it takes to communicate data between the machines. For dynamic distributed grids it is unrealistic to know exact parameters of the communication hardware and the current communication traffic and we should rely on a model of the network performance to estimate the message delivery time. Our approach to a construction of such a model is based on observation of the messages delivery time with various message sizes and time scales. We record these observations in a database and use them to build a model of the message delivery time. Our experiments show presence of multiple bands in the logarithm of the message delivery times. These multiple bands represent multiple paths messages travel between the grid machines and are incorporated in our multiband model.

Surgical scrubbing: can we clean up our carbon footprints by washing our hands?

PubMed

Somner, J E A; Stone, N; Koukkoulli, A; Scott, K M; Field, A R; Zygmunt, J

2008-11-01

A growing scientific consensus states that the global climate is changing and that human activity is responsible for these changes. It folLows that each of us has a responsibility to look at how our own lives impact on the environment. This study aimed to investigate water use during surgical scrubbing. Two water delivery systems were assessed to see whether technological innovation can promote more 'environmentally friendly' scrubbing behaviour. At least 10 different individuals, comprising surgeons, assistants and scrub nurses, were observed at two sites. Twenty-five separate surgical scrubs were observed in each location and the length of time for which the tap was on recorded. The tap was on during surgical scrubbing for a mean of 2 min 23 s at Gartnavel General Hospital (maximum: 4 min 37 s; minimum: 49 s; SD: 55 s) and for a mean of 1 min 7 s at Stobhill Hospital (maximum: 2 min 25 s; minimum: 19 s; SD: 33 s). The mean 'tap on' time (in seconds) at Gartnavel was significantly greater than that at Stobhill [t(39.5)=P<0.001]. A different tap design resulted in a net saving of 5.7 L of hot water, approximately 600 kJ of energy and 80 g of carbon dioxide emitted per surgical scrub. Surgical scrubbing is a ubiquitous procedure performed daily in healthcare settings. A simple technological solution can reduce water and energy use by modifying hand-washing behaviour and thereby reduce the carbon footprint of surgical scrubbing.

Development of a gastroretentive pulsatile drug delivery platform.

PubMed

Thitinan, Sumalee; McConville, Jason T

2012-04-01

To develop a novel gastroretentive pulsatile drug delivery platform by combining the advantages of floating dosage forms for the stomach and pulsatile drug delivery systems. A gastric fluid impermeable capsule body was used as a vessel to contain one or more drug layer(s) as well as one or more lag-time controlling layer(s). A controlled amount of air was sealed in the innermost portion of the capsule body to reduce the overall density of the drug delivery platform, enabling gastric floatation. An optimal mass fill inside the gastric fluid impermeable capsule body enabled buoyancy in a vertical orientation to provide a constant surface area for controlled erosion of the lag-time controlling layer. The lag-time controlling layer consisted of a swellable polymer, which rapidly formed a gel to seal the mouth of capsule body and act as a barrier to gastric fluid ingress. By varying the composition of the lag-time controlling layer, it was possible to selectively program the onset of the pulsatile delivery of a drug. This new delivery platform offers a new method of delivery for a variety of suitable drugs targeted in chronopharmaceutical therapy. This strategy could ultimately improve drug efficacy and patient compliance, and reduce harmful side effects by scaling back doses of drug administered. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

A best on-line algorithm for single machine scheduling the equal length jobs with the special chain precedence and delivery time

NASA Astrophysics Data System (ADS)

Gu, Cunchang; Mu, Yundong

2013-03-01

In this paper, we consider a single machine on-line scheduling problem with the special chains precedence and delivery time. All jobs arrive over time. The chains chainsi arrive at time ri , it is known that the processing and delivery time of each job on the chain satisfy one special condition CD a forehand: if the job J(i)j is the predecessor of the job J(i)k on the chain chaini, then they satisfy p(i)j = p(i)k = p >= qj >= qk , i = 1,2, ---,n , where pj and qj denote the processing time and the delivery time of the job Jj respectively. Obviously, if the arrival jobs have no chains precedence, it shows that the length of the corresponding chain is 1. The objective is to minimize the time by which all jobs have been delivered. We provide an on-line algorithm with a competitive ratio of √2 , and the result is the best possible.

Atmospheric Rivers Enhanced Water Delivery to Southwestern North America at the Last Glacial Maximum

NASA Astrophysics Data System (ADS)

Lora, J. M.; Mitchell, J.; Risi, C. M.; Tripati, A. K.

2015-12-01

Proxy reconstructions of the late Pleistocene paleoclimate indicate that southwestern North America was significantly more wet at the Last Glacial Maximum (LGM; ~21 ka) than in the present. Pluvial paleolakes were abundant throughout the Great Basin and as far south as the modern Mojave Desert. The source of precipitation that fed these lakes and the role of evaporation in the hydrologic balance are debated. A leading hypothesis is increased Pacific winter storm frequency as a result of the jet stream being split or shifted south by the North American ice sheets. Alternative hypotheses include enhanced monsoonal precipitation, a re-routing of the storm track across the continent, and/or reduced evaporation. Using LGM simulations from the PMIP3 ensemble and the LMDZ general circulation model, and comparing to proxy records of LGM precipitation in the region, we find that atmospheric rivers, narrow filaments of humid tropical air, were strengthened over the eastern Pacific during glacial intervals and directed into southern California. A strengthened Aleutian Low and a weakened North Pacific High produced a mean state conducive to this strong, south-shifted atmospheric river system, which enhanced moisture delivery into the southwestern part of the Great Basin.

High-power picosecond pulse delivery through hollow core photonic band gap fibers

NASA Astrophysics Data System (ADS)

Michieletto, Mattia; Johansen, Mette M.; Lyngsø, Jens K.; Lægsgaard, Jesper; Bang, Ole; Alkeskjold, Thomas T.

2016-03-01

We demonstrated robust and bend insensitive fiber delivery of high power laser with diffraction limited beam quality for two different kinds of hollow core band gap fibers. The light source for this experiment consists of ytterbium-doped double clad fiber aeroGAIN-ROD-PM85 in a high power amplifier setup. It provided 22ps pulses with a maximum average power of 95W, 40MHz repetition rate at 1032nm (~2.4μJ pulse energy), with M2 <1.3. We determined the facet damage threshold for a 7-cells hollow core photonic bandgap fiber and showed up to 59W average power output for a 5 meters fiber. The damage threshold for a 19-cell hollow core photonic bandgap fiber exceeded the maximum power provided by the light source and up to 76W average output power was demonstrated for a 1m fiber. In both cases, no special attention was needed to mitigate bend sensitivity. The fibers were coiled on 8 centimeters radius spools and even lower bending radii were present. In addition, stimulated rotational Raman scattering arising from nitrogen molecules was measured through a 42m long 19 cell hollow core fiber.

SU-E-T-62: A Preliminary Experience of Using EPID Transit Dosimetry for Monitoring Daily Dose Variations in Radiation Treatment Delivery

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

Yao, R; Chisela, W

2015-06-15

Purpose: To investigate the use of EPID transit dosimetry for monitoring daily dose variations in radiation treatment delivery. Methods: A patient with head and neck cancer treated using nine field IMRT beams was used in this study. The prescription was 45 Gy in 25 fractions. A KV CBCT was acquired before each treatment on a Varian NTX linear accelerator. Integrated images using MV EPID were acquired for each treatment beam. Planning CT images, treatment plan, and daily integrated images were imported into a commercial QA software Dosimetry Check (v4r4 Math Resolutions, LLC, Columbia, MD) to calculate 3D dose of themore » day assuming 25 fractions treatment. Planning CT images were deformed and registered to each daily CBCT using Varian SmartAdapt (v11.MR2). ROIs were then propagated from planning CT to daily CBCT. The correlation between maximum, average dose of ROIs and ROI volume, center of mass shift, Dice Similarity Coefficient (DSC) were investigated. Results: Not all parameters investigated showed strong correlations. For PTV and CTV, the average dose has inverse correlation with their volume change (correlation coefficient −0.52, −0.50, respectively) and DSC (−0.59, −0.59, respectively). The average dose of right parotid has correlation with its volume change (0.56). The maximum dose of spinal cord has correlation with the center of mass superior-inferior shift (0.52) and inverse correlation with the center of mass anterior-posterior shift (−0.73). Conclusion: Transit dosimetry using EPID images collected during treatment delivery offers great potential to monitor daily dose variations due to patient anatomy change, motion, and setup errors in radiation treatment delivery. It can provide a patient-specific QA tool valuable for adaptive radiation therapy. Further work is needed to validate the technique.« less

Real-time estimation of prostate tumor rotation and translation with a kV imaging system based on an iterative closest point algorithm.

PubMed

Tehrani, Joubin Nasehi; O'Brien, Ricky T; Poulsen, Per Rugaard; Keall, Paul

2013-12-07

Previous studies have shown that during cancer radiotherapy a small translation or rotation of the tumor can lead to errors in dose delivery. Current best practice in radiotherapy accounts for tumor translations, but is unable to address rotation due to a lack of a reliable real-time estimate. We have developed a method based on the iterative closest point (ICP) algorithm that can compute rotation from kilovoltage x-ray images acquired during radiation treatment delivery. A total of 11 748 kilovoltage (kV) images acquired from ten patients (one fraction for each patient) were used to evaluate our tumor rotation algorithm. For each kV image, the three dimensional coordinates of three fiducial markers inside the prostate were calculated. The three dimensional coordinates were used as input to the ICP algorithm to calculate the real-time tumor rotation and translation around three axes. The results show that the root mean square error was improved for real-time calculation of tumor displacement from a mean of 0.97 mm with the stand alone translation to a mean of 0.16 mm by adding real-time rotation and translation displacement with the ICP algorithm. The standard deviation (SD) of rotation for the ten patients was 2.3°, 0.89° and 0.72° for rotation around the right-left (RL), anterior-posterior (AP) and superior-inferior (SI) directions respectively. The correlation between all six degrees of freedom showed that the highest correlation belonged to the AP and SI translation with a correlation of 0.67. The second highest correlation in our study was between the rotation around RL and rotation around AP, with a correlation of -0.33. Our real-time algorithm for calculation of rotation also confirms previous studies that have shown the maximum SD belongs to AP translation and rotation around RL. ICP is a reliable and fast algorithm for estimating real-time tumor rotation which could create a pathway to investigational clinical treatment studies requiring real-time measurement and adaptation to tumor rotation.

Real-time estimation of prostate tumor rotation and translation with a kV imaging system based on an iterative closest point algorithm

NASA Astrophysics Data System (ADS)

Nasehi Tehrani, Joubin; O'Brien, Ricky T.; Rugaard Poulsen, Per; Keall, Paul

2013-12-01

Previous studies have shown that during cancer radiotherapy a small translation or rotation of the tumor can lead to errors in dose delivery. Current best practice in radiotherapy accounts for tumor translations, but is unable to address rotation due to a lack of a reliable real-time estimate. We have developed a method based on the iterative closest point (ICP) algorithm that can compute rotation from kilovoltage x-ray images acquired during radiation treatment delivery. A total of 11 748 kilovoltage (kV) images acquired from ten patients (one fraction for each patient) were used to evaluate our tumor rotation algorithm. For each kV image, the three dimensional coordinates of three fiducial markers inside the prostate were calculated. The three dimensional coordinates were used as input to the ICP algorithm to calculate the real-time tumor rotation and translation around three axes. The results show that the root mean square error was improved for real-time calculation of tumor displacement from a mean of 0.97 mm with the stand alone translation to a mean of 0.16 mm by adding real-time rotation and translation displacement with the ICP algorithm. The standard deviation (SD) of rotation for the ten patients was 2.3°, 0.89° and 0.72° for rotation around the right-left (RL), anterior-posterior (AP) and superior-inferior (SI) directions respectively. The correlation between all six degrees of freedom showed that the highest correlation belonged to the AP and SI translation with a correlation of 0.67. The second highest correlation in our study was between the rotation around RL and rotation around AP, with a correlation of -0.33. Our real-time algorithm for calculation of rotation also confirms previous studies that have shown the maximum SD belongs to AP translation and rotation around RL. ICP is a reliable and fast algorithm for estimating real-time tumor rotation which could create a pathway to investigational clinical treatment studies requiring real-time measurement and adaptation to tumor rotation.

Spray-dried powders enhance vaginal siRNA delivery by potentially modulating the mucus molecular sieve structure.

PubMed

Wu, Na; Zhang, Xinxin; Li, Feifei; Zhang, Tao; Gan, Yong; Li, Juan

2015-01-01

Vaginal small interfering RNA (siRNA) delivery provides a promising strategy for the prevention and treatment of vaginal diseases. However, the densely cross-linked mucus layer on the vaginal wall severely restricts nanoparticle-mediated siRNA delivery to the vaginal epithelium. In order to overcome this barrier and enhance vaginal mucus penetration, we prepared spray-dried powders containing siRNA-loaded nanoparticles. Powders with Pluronic F127 (F127), hydroxypropyl methyl cellulose (HPMC), and mannitol as carriers were obtained using an ultrasound-assisted spray-drying technique. Highly dispersed dry powders with diameters of 5-15 μm were produced. These powders showed effective siRNA protection and sustained release. The mucus-penetrating properties of the powders differed depending on their compositions. They exhibited different potential of opening mesh size of molecular sieve in simulated vaginal mucus system. A powder formulation with 0.6% F127 and 0.1% HPMC produced the maximum increase in the pore size of the model gel used to simulate vaginal mucus by rapidly extracting water from the gel and interacting with the gel; the resulting modulation of the molecular sieve effect achieved a 17.8-fold improvement of siRNA delivery in vaginal tract and effective siRNA delivery to the epithelium. This study suggests that powder formulations with optimized compositions have the potential to alter the steric barrier posed by mucus and hold promise for effective vaginal siRNA delivery.

Experimentally studied dynamic dose interplay does not meaningfully affect target dose in VMAT SBRT lung treatments.

PubMed

Stambaugh, Cassandra; Nelms, Benjamin E; Dilling, Thomas; Stevens, Craig; Latifi, Kujtim; Zhang, Geoffrey; Moros, Eduardo; Feygelman, Vladimir

2013-09-01

The effects of respiratory motion on the tumor dose can be divided into the gradient and interplay effects. While the interplay effect is likely to average out over a large number of fractions, it may play a role in hypofractionated [stereotactic body radiation therapy (SBRT)] treatments. This subject has been extensively studied for intensity modulated radiation therapy but less so for volumetric modulated arc therapy (VMAT), particularly in application to hypofractionated regimens. Also, no experimental study has provided full four-dimensional (4D) dose reconstruction in this scenario. The authors demonstrate how a recently described motion perturbation method, with full 4D dose reconstruction, is applied to describe the gradient and interplay effects during VMAT lung SBRT treatments. VMAT dose delivered to a moving target in a patient can be reconstructed by applying perturbations to the treatment planning system-calculated static 3D dose. Ten SBRT patients treated with 6 MV VMAT beams in five fractions were selected. The target motion (motion kernel) was approximated by 3D rigid body translation, with the tumor centroids defined on the ten phases of the 4DCT. The motion was assumed to be periodic, with the period T being an average from the empirical 4DCT respiratory trace. The real observed tumor motion (total displacement ≤ 8 mm) was evaluated first. Then, the motion range was artificially increased to 2 or 3 cm. Finally, T was increased to 60 s. While not realistic, making T comparable to the delivery time elucidates if the interplay effect can be observed. For a single fraction, the authors quantified the interplay effect as the maximum difference in the target dosimetric indices, most importantly the near-minimum dose (D99%), between all possible starting phases. For the three- and five-fractions, statistical simulations were performed when substantial interplay was found. For the motion amplitudes and periods obtained from the 4DCT, the interplay effect is negligible (<0.2%). It is also small (0.9% average, 2.2% maximum) when the target excursion increased to 2-3 cm. Only with large motion and increased period (60 s) was a significant interplay effect observed, with D99% ranging from 16% low to 17% high. The interplay effect was statistically significantly lower for the three- and five-fraction statistical simulations. Overall, the gradient effect dominates the clinical situation. A novel method was used to reconstruct the volumetric dose to a moving tumor during lung SBRT VMAT deliveries. With the studied planning and treatment technique for realistic motion periods, regardless of the amplitude, the interplay has nearly no impact on the near-minimum dose. The interplay effect was observed, for study purposes only, with the period comparable to the VMAT delivery time.

Assessing a commercially available sports drink on exogenous carbohydrate oxidation, fluid delivery and sustained exercise performance

PubMed Central

2014-01-01

Background Whilst exogenous carbohydrate oxidation (CHOEXO) is influenced by mono- and disaccharide combinations, debate exists whether such beverages enhance fluid delivery and exercise performance. Therefore, this study aimed to ascertain CHOEXO, fluid delivery and performance times of a commercially available maltodextrin/ fructose beverage in comparison to an isocaloric maltodextrin beverage and placebo. Methods Fourteen club level cyclists (age: 31.79 ± 10.02 years; height: 1.79 ± 0.06 m; weight: 73.69 ± 9.24 kg; VO2max: 60.38 ± 9.36 mL · kg·-1 min-1) performed three trials involving 2.5 hours continuous exercise at 50% maximum power output (Wmax: 176.71 ± 25.92 W) followed by a 60 km cycling performance test. Throughout each trial, athletes were randomly assigned, in a double-blind manner, either: (1) 1.1 g · min-1 maltodextrin + 0.6 g · min-1 fructose (MD + F), (2) 1.7 g · min-1 of maltodextrin (MD) or (3) flavoured water (P). In addition, the test beverage at 60 minutes contained 5.0 g of deuterium oxide (2H2O) to assess quantification of fluid delivery. Expired air samples were analysed for CHOEXO according to the 13C/12C ratio method using gas chromatography continuous flow isotope ratio mass spectrometry. Results Peak CHOEXO was significantly greater in the final 30 minutes of submaximal exercise with MD + F and MD compared to P (1.45 ± 0.09 g · min-1, 1.07 ± 0.03 g · min-1and 0.00 ± 0.01 g · min-1 respectively, P < 0.0001), and significantly greater for MD + F compared to MD (P = 0.005). The overall appearance of 2H2O in plasma was significantly greater in both P and MD + F compared to MD (100.27 ± 3.57 ppm, 92.57 ± 2.94 ppm and 78.18 ± 4.07 ppm respectively, P < 0.003). There was no significant difference in fluid delivery between P and MD + F (P = 0.078). Performance times significantly improved with MD + F compared with both MD (by 7 min 22 s ± 1 min 56 s, or 7.2%) and P (by 6 min 35 s ± 2 min 33 s, or 6.5%, P < 0.05) over 60 km. Conclusions A commercially available maltodextrin-fructose beverage improves CHOEXO and fluid delivery, which may benefit individuals during sustained moderate intensity exercise. The greater CHOEXO observed when consuming a maltodextrin-fructose beverage may support improved performance times. PMID:24589205

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.

An efficient PEGylated liposomal nanocarrier containing cell-penetrating peptide and pH-sensitive hydrazone bond for enhancing tumor-targeted drug delivery.

PubMed

Ding, Yuan; Sun, Dan; Wang, Gui-Ling; Yang, Hong-Ge; Xu, Hai-Feng; Chen, Jian-Hua; Xie, Ying; Wang, Zhi-Qiang

2015-01-01

Cell-penetrating peptides (CPPs) as small molecular transporters with abilities of cell penetrating, internalization, and endosomal escape have potential prospect in drug delivery systems. However, a bottleneck hampering their application is the poor specificity for cells. By utilizing the function of hydration shell of polyethylene glycol (PEG) and acid sensitivity of hydrazone bond, we constructed a kind of CPP-modified pH-sensitive PEGylated liposomes (CPPL) to improve the selectivity of these peptides for tumor targeting. In CPPL, CPP was directly attached to liposome surfaces via coupling with stearate (STR) to avoid the hindrance of PEG as a linker on the penetrating efficiency of CPP. A PEG derivative by conjugating PEG with STR via acid-degradable hydrazone bond (PEG2000-Hz-STR, PHS) was synthesized. High-performance liquid chromatography and flow cytometry demonstrated that PHS was stable at normal neutral conditions and PEG could be completely cleaved from liposome surface to expose CPP under acidic environments in tumor. An optimal CPP density on liposomes was screened to guaranty a maximum targeting efficiency on tumor cells as well as not being captured by normal cells that consequently lead to a long circulation in blood. In vitro and in vivo studies indicated, in 4 mol% CPP of lipid modified system, that CPP exerted higher efficiency on internalizing the liposomes into targeted subcellular compartments while remaining inactive and free from opsonins at a maximum extent in systemic circulation. The 4% CPPL as a drug delivery system will have great potential in the clinical application of anticancer drugs in future.

An efficient PEGylated liposomal nanocarrier containing cell-penetrating peptide and pH-sensitive hydrazone bond for enhancing tumor-targeted drug delivery

PubMed Central

Ding, Yuan; Sun, Dan; Wang, Gui-Ling; Yang, Hong-Ge; Xu, Hai-Feng; Chen, Jian-Hua; Xie, Ying; Wang, Zhi-Qiang

2015-01-01

Cell-penetrating peptides (CPPs) as small molecular transporters with abilities of cell penetrating, internalization, and endosomal escape have potential prospect in drug delivery systems. However, a bottleneck hampering their application is the poor specificity for cells. By utilizing the function of hydration shell of polyethylene glycol (PEG) and acid sensitivity of hydrazone bond, we constructed a kind of CPP-modified pH-sensitive PEGylated liposomes (CPPL) to improve the selectivity of these peptides for tumor targeting. In CPPL, CPP was directly attached to liposome surfaces via coupling with stearate (STR) to avoid the hindrance of PEG as a linker on the penetrating efficiency of CPP. A PEG derivative by conjugating PEG with STR via acid-degradable hydrazone bond (PEG2000-Hz-STR, PHS) was synthesized. High-performance liquid chromatography and flow cytometry demonstrated that PHS was stable at normal neutral conditions and PEG could be completely cleaved from liposome surface to expose CPP under acidic environments in tumor. An optimal CPP density on liposomes was screened to guaranty a maximum targeting efficiency on tumor cells as well as not being captured by normal cells that consequently lead to a long circulation in blood. In vitro and in vivo studies indicated, in 4 mol% CPP of lipid modified system, that CPP exerted higher efficiency on internalizing the liposomes into targeted subcellular compartments while remaining inactive and free from opsonins at a maximum extent in systemic circulation. The 4% CPPL as a drug delivery system will have great potential in the clinical application of anticancer drugs in future. PMID:26491292

Structural, Chemical, and Mechanical Properties of Pressure Garments as a Function of Simulated Use and Repeated Laundering.

PubMed

Malara, Megan M; Kim, Jayne Y; Clark, J Alexander; Blackstone, Britani N; Ruegsegger, Mark A; Bailey, J Kevin; Supp, Dorothy M; Powell, Heather M

2018-06-13

Pressure garments are widely employed for management of postburn scarring. Although pressure magnitude has been linked to efficacy, maintenance of uniform pressure delivery is challenging. An understanding of garment fabric properties is needed to optimize pressure delivery for the duration of garment use. To address this issue, compression vests were manufactured using two commonly used fabrics, Powernet or Dri-Tek Tricot, to achieve 10% reduction in circumference for a child-sized mannequin. Applied pressure was tracked on five anatomical sites over 23 hours, before laundering or after one and five laundering cycles. Load relaxation and fatigue of fabrics were tested before laundering or after one and five laundering cycles, and structural analysis via scanning electron microscopy was performed. Prior to laundering, pressure vests fabricated using Powernet or Dri-Tek Tricot generated a maximum pressure on the mannequin of 20 and 23 mm Hg, respectively. With both fabrics, pressure decreased during daily wear. Following five laundering cycles, Dri-Tek Tricot vests delivered a maximum of 7 vs 15 mm Hg pressure for Powernet at the same site. In cyclic tensile and load relaxation tests, exerted force correlated with fabric weave orientation with greatest force measured parallel to a fabric's long axis. The results demonstrate that Powernet exhibited the greatest applied force with the least garment fatigue. Fabric orientation with respect to the primary direction of tension was a critical factor in pressure generation and maintenance. This study suggests that fabrication of garments using Powernet with its long axis parallel to patient's body part circumference may enhance the magnitude and maintenance of pressure delivery.

A New Low-frequency Sonophoresis System Combined with Ultrasonic Motor and Transducer

NASA Astrophysics Data System (ADS)

Zhu, Pancheng; Peng, Hanmin; Yang, Jianzhi; Mao, Ting; Sheng, Juan

2018-03-01

Low frequency sonophoresis (LFS) is currently being attempted as a transdermal drug delivery method in clinical areas. However, it lacks both an effective control method and the equipment to satisfy the varying drug dosage requirements of individual patients. Herein, a novel method aimed at controlling permeability is proposed and developed, using a pressure control strategy which is based on an accurate, adjustable and non-invasive ultrasound transdermal drug delivery system in in vitro LFS. The system mainly consists of a lead screw linear ultrasonic motor and an ultrasonic transducer, in which the former offers pressure and the latter provides ultrasound wave in the liquid. The ultrasound can enhance non-invasive permeation and the pressure from the motor can control the permeability. The calculated and experimental results demonstrate that the maximum pressure on artificial skin is under the area with the maximum vibration amplitude of the ultrasonic transducer, and the total pressure consists of acoustic pressure from the transducer and approximate static pressure from the motor. Changing the static pressure from the ultrasonic motor can effectively control the non-invasive permeability, by adjusting the duty ratio or the amplitude of the motor’s driving voltage. In addition, the permeability control of calcein by thrust control is realized in 15 min, indicating the suitability of this method for application in accurate medical technology. The obtained results reveal that the issue of difficult permeability control can be addressed, using this control method in in vitro LFS to open up a route to the design of accurate drug delivery technology for individual patients.

The degree of labor pain at the time of epidural analgesia in nulliparous women influences the obstetric outcome.

PubMed

Woo, Jae Hee; Kim, Jong Hak; Lee, Guie Yong; Baik, Hee Jung; Kim, Youn Jin; Chung, Rack Kyung; Yun, Du Gyun; Lim, Chae Hwang

2015-06-01

The increased pain at the latent phase can be associated with dysfunctional labor as well as increases in cesarean delivery frequency. We aimed to research the effect of the degree of pain at the time of epidural analgesia on the entire labor process including the mode of delivery. We performed epidural analgesia to 102 nulliparous women on patients' request. We divided the group into three based on NRS (numeric rating scale) at the moment of epidural analgesia; mild pain, NRS 1-4; moderate pain, NRS 5-7; severe pain, NRS 8-10. The primary outcome was the mode of delivery (normal labor or cesarean delivery). There were significant differences in the mode of delivery among groups. Patients with severe labor pain had a significantly higher cesarean delivery compared to patients with moderate labor pain (P = 0.006). The duration of the first and second stage of labor, fetal heart rate, use of oxytocin and premature rupture of membranes had no differences in the three groups. Our research showed that the degree of pain at the time of epidural analgesia request might influence the rate of cesarean delivery. Further research would be necessary for clarifying the mechanism that the augmentation of pain affects the mode of delivery.

National health insurance, physician financial incentives, and primary cesarean deliveries in Taiwan.

PubMed

Tsai, Yi-Wen; Hu, Teh-Wei

2002-09-01

Taiwan's National Health Insurance Program (NHI) was implemented on March 1, 1995. This study analyzed the influences of the Case Payment method of reimbursement for inpatient care and of physician financial incentives on a woman's choice for primary cesarean delivery. Logistic regressions were used to analyze 11 788 first-time deliveries in a nonprofit hospital system between March 1, 1994, and February 29, 1996. After implementation of the NHI's Case Payment scheme, the likelihood that a woman would choose primary cesarean delivery increased by four to five times compared with the choice behavior of uninsured individuals prior to NHI (P <.0001). Out-of-pocket payment discourages the selection of primary cesarean delivery. No robust statistics were found relating physician financial incentives to delivery choice.

Optimization of the temporal pattern of radiation: An IMRT based study

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

Altman, Michael B.; Chmura, Steven J.; Deasy, Joseph O.

Purpose: To investigate how the temporal pattern of dose applied during a single-intensity modulated radiation therapy (IMRT) fraction can be arranged to maximize or minimize cell kill. Methods and Materials: Using the linear-quadratic repair-time model and a simplified IMRT delivery pattern model, the surviving fraction of cells for a single fraction was calculated for all permutations of the dose delivery pattern for an array of clinically based IMRT cases. Maximization of cell kill was achieved by concentrating the highest doses in the middle of a fraction, while minimization was achieved by spreading the highest doses between the beginning and end.more » The percent difference between maximum and minimum cell kill (%Diff{sub min/max}) and the difference between maximum and minimum total doses normalized to 2 Gy/fx ({delta}NTD{sub 2Gy}) was calculated for varying fraction durations (T), {alpha}/{beta} ratios, and doses/fx. Results: %Diff{sub min/max} and {delta}NTD{sub 2Gy} both increased with increasing T and with decreasing {alpha}/{beta}. The largest increases occurred with dose/fx. With {alpha}/{beta} = 3 Gy and 30 min/fx, %Diff{sub min/max} ranged from 2.7-5.3% for 2 Gy/fx to 48.6-74.1% for 10 Gy/fx, whereas {delta}NTD{sub 2Gy} ranged from 1.2 Gy-2.4 Gy for 30 fractions of 2 Gy/fx to 2.3-4.8 Gy for 2 fractions of 10.84 Gy/fx. Using {alpha}/{beta} = 1.5 Gy, an analysis of prostate hypofractionation schemes yielded differences in clinical outcome based on the pattern of applied dose ranging from 3.2%-6.1% of the treated population. Conclusions: Rearrangement of the temporal pattern of dose for a single IMRT fraction could be used to optimize cell kill and to directly, though modestly, affect treatment outcome.« less

Intensity-modulated radiation therapy and volumetric-modulated arc therapy for adult craniospinal irradiation—A comparison with traditional techniques

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

Studenski, Matthew T., E-mail: matthew.studenski@jeffersonhospital.org; Shen, Xinglei; Yu, Yan

2013-04-01

Craniospinal irradiation (CSI) poses a challenging planning process because of the complex target volume. Traditional 3D conformal CSI does not spare any critical organs, resulting in toxicity in patients. Here the dosimetric advantages of intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) are compared with classic conformal planning in adults for both cranial and spine fields to develop a clinically feasible technique that is both effective and efficient. Ten adult patients treated with CSI were retrospectively identified. For the cranial fields, 5-field IMRT and dual 356° VMAT arcs were compared with opposed lateral 3D conformal radiotherapy (3D-CRT) fields. Formore » the spine fields, traditional posterior-anterior (PA) PA fields were compared with isocentric 5-field IMRT plans and single 200° VMAT arcs. Two adult patients have been treated using this IMRT technique to date and extensive quality assurance, especially for the junction regions, was performed. For the cranial fields, the IMRT technique had the highest planned target volume (PTV) maximum and was the least efficient, whereas the VMAT technique provided the greatest parotid sparing with better efficiency. 3D-CRT provided the most efficient delivery but with the highest parotid dose. For the spine fields, VMAT provided the best PTV coverage but had the highest mean dose to all organs at risk (OAR). 3D-CRT had the highest PTV and OAR maximum doses but was the most efficient. IMRT provides the greatest OAR sparing but the longest delivery time. For those patients with unresectable disease that can benefit from a higher, definitive dose, 3D-CRT–opposed laterals are the most clinically feasible technique for cranial fields and for spine fields. Although inefficient, the IMRT technique is the most clinically feasible because of the increased mean OAR dose with the VMAT technique. Quality assurance of the beams, especially the junction regions, is essential.« less

Comparison of sorafenib-loaded poly (lactic/glycolic) acid and DPPC liposome nanoparticles in the in vitro treatment of renal cell carcinoma.

PubMed

Liu, James; Boonkaew, Benjawan; Arora, Jaspreet; Mandava, Sree Harsha; Maddox, Michael M; Chava, Srinivas; Callaghan, Cameron; He, Jibao; Dash, Srikanta; John, Vijay T; Lee, Benjamin R

2015-03-01

The objective of this study is to develop and compare several Sorafenib-loaded biocompatible nanoparticle models in order to optimize drug delivery and tumor cellular kill thereby improving the quality of Sorafenib-regimented chemotherapy. Sorafenib-loaded poly (lactic-co-glycolic) acid (PLGA), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes, and hydrophobically modified chitosan (HMC)-coated DPPC liposomes were evaluated for several characteristics including zeta potential, drug loading, and release profile. Cytotoxicity and uptake trials were also studied using cell line RCC 786-0, a human metastatic clear cell histology renal cell carcinoma cell line. Sorafenib-loaded PLGA particles and HMC-coated DPPC liposomes exhibited significantly improved cell kill compared to Sorafenib alone at lower concentrations, namely 10-15 and 5-15 μM from 24 to 96 h, respectively. At maximum dosage and time (15 μM and 96 h), Sorafenib-loaded PLGA and HMC-coated liposomes killed 88.3 ± 1.8% and 98 ± 1.1% of all tumor cells, significant values compared with Sorafenib 81.8 ± 1.7% (p < 0.01). Likewise, HMC coating substantially improved cell kill for liposome model for all concentrations (5-15 μM) and at time points (24-96 h) (p < 0.01). PLGA and HMC-coated liposomes are promising platforms for drug delivery of Sorafenib. Because of different particle characteristics of PLGA and liposomes, each model can be further developed for unique clinical modalities. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Contrast Sensitivity With a Subretinal Prosthesis and Implications for Efficient Delivery of Visual Information

PubMed Central

Goetz, Georges; Smith, Richard; Lei, Xin; Galambos, Ludwig; Kamins, Theodore; Mathieson, Keith; Sher, Alexander; Palanker, Daniel

2015-01-01

Purpose To evaluate the contrast sensitivity of a degenerate retina stimulated by a photovoltaic subretinal prosthesis, and assess the impact of low contrast sensitivity on transmission of visual information. Methods We measure ex vivo the full-field contrast sensitivity of healthy rat retina stimulated with white light, and the contrast sensitivity of degenerate rat retina stimulated with a subretinal prosthesis at frequencies exceeding flicker fusion (>20 Hz). Effects of eye movements on retinal ganglion cell (RGC) activity are simulated using a linear–nonlinear model of the retina. Results Retinal ganglion cells adapt to high frequency stimulation of constant intensity, and respond transiently to changes in illumination of the implant, exhibiting responses to ON-sets, OFF-sets, and both ON- and OFF-sets of light. The percentage of cells with an OFF response decreases with progression of the degeneration, indicating that OFF responses are likely mediated by photoreceptors. Prosthetic vision exhibits reduced contrast sensitivity and dynamic range, with 65% contrast changes required to elicit responses, as compared to the 3% (OFF) to 7% (ON) changes with visible light. The maximum number of action potentials elicited with prosthetic stimulation is at most half of its natural counterpart for the ON pathway. Our model predicts that for most visual scenes, contrast sensitivity of prosthetic vision is insufficient for triggering RGC activity by fixational eye movements. Conclusions Contrast sensitivity of prosthetic vision is 10 times lower than normal, and dynamic range is two times below natural. Low contrast sensitivity and lack of OFF responses hamper delivery of visual information via a subretinal prosthesis. PMID:26540657

Laminar flow assisted anisotropic bacteria absorption for chemotaxis delivery of bacteria-attached microparticle

NASA Astrophysics Data System (ADS)

Huh, Keon; Oh, Darong; Son, Seok Young; Yoo, Hyung Jung; Song, Byeonghwa; Cho, Dong-il Dan; Seo, Jong-Mo; Kim, Sung Jae

2016-12-01

The concepts of microrobots has been drawn significant attentions recently since its unprecedented applicability in nanotechnology and biomedical field. Bacteria attached microparticles presented in this work are one of pioneering microrobot technology for self-propulsion or producing kinetic energy from ambient for their motions. Microfluidic device, especially utilizing laminar flow characteristics, were employed for anisotropic attachment of Salmonella typhimurium flagellated chemotactic bacteria to 30 um × 30 um and 50 um × 50 um microparticles that made of biodegradable polymer. Any toxic chemicals or harmful treatments were excluded during the attachment process and it finished within 100 s for the anisotropic attachment. The attachments were directly confirmed by fluorescent intensity changes and SEM visualization. Chemotaxis motions were tracked using aspartate and the maximum velocity of the bacteria-attached microrobot was measured to be 5 um/s which is comparable to prior state of art technologies. This reusable and scalable method could play a key role in chemotaxis delivery of functional microparticles such as drug delivery system.

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.

Delivery of disulfiram into breast cancer cells using folate-receptor-targeted PLGA-PEG nanoparticles: in vitro and in vivo investigations.

PubMed

Fasehee, Hamidreza; Dinarvand, Rassoul; Ghavamzadeh, Ardeshir; Esfandyari-Manesh, Mehdi; Moradian, Hanieh; Faghihi, Shahab; Ghaffari, Seyed Hamidollah

2016-04-21

A folate-receptor-targeted poly (lactide-co-Glycolide) (PLGA)-Polyethylene glycol (PEG) nanoparticle is developed for encapsulation and delivery of disulfiram into breast cancer cells. After a comprehensive characterization of nanoparticles, cell cytotoxicity, apoptosis induction, cellular uptake and intracellular level of reactive oxygen species are analyzed. In vivo acute and chronic toxicity of nanoparticles and their efficacy on inhibition of breast cancer tumor growth is studied. The folate-receptor-targeted nanoparticles are internalized into the cells, induce reactive oxygen species formation, induce apoptosis and inhibit cell proliferation more efficiently compared to the untargeted nanoparticles. The acute and toxicity test show the maximum dose of disulfiram equivalent of nanoparticles for intra-venous injection is 6 mg/kg while show significant decrease in the breast cancer tumor growth rate. It is believed that the developed formulation could be used as a potential vehicle for successful delivery of disulfiram, an old and inexpensive drug, into breast cancer cells and other solid tumors.

Fine-tuned PEGylation of chitosan to maintain optimal siRNA-nanoplex bioactivity.

PubMed

Guţoaia, Andra; Schuster, Liane; Margutti, Simona; Laufer, Stefan; Schlosshauer, Burkhard; Krastev, Rumen; Stoll, Dieter; Hartmann, Hanna

2016-06-05

Polyethylene glycol (PEG) is a widely used modification for drug delivery systems. It reduces undesired interaction with biological components, aggregation of complexes and serves as a hydrophilic linker of ligands for targeted drug delivery. However, PEGylation can also lead to undesired changes in physicochemical characteristics of chitosan/siRNA nanoplexes and hamper gene silencing. To address this conflicting issue, PEG-chitosan copolymers were synthesized with stepwise increasing degrees of PEG substitution (1.5% to 8.0%). Subsequently formed PEG-chitosan/siRNA nanoplexes were characterized physicochemically and biologically. The results showed that small ratios of chitosan PEGylation did not affect nanoplex stability and density. However, higher PEGylation ratios reduced nanoplex size and charge, as well as cell uptake and final siRNA knockdown efficiency. Therefore, we recommend fine-tuning of PEGylation ratios to generate PEG-chitosan/siRNA delivery systems with maximum bioactivity. The degree of PEGylation for chitosan/siRNA nanoplexes should be kept low in order to maintain optimal nanoplex efficiency. Copyright © 2016 Elsevier Ltd. All rights reserved.

Retrieval-travel-time model for free-fall-flow-rack automated storage and retrieval system

NASA Astrophysics Data System (ADS)

Metahri, Dhiyaeddine; Hachemi, Khalid

2018-03-01

Automated storage and retrieval systems (AS/RSs) are material handling systems that are frequently used in manufacturing and distribution centers. The modelling of the retrieval-travel time of an AS/RS (expected product delivery time) is practically important, because it allows us to evaluate and improve the system throughput. The free-fall-flow-rack AS/RS has emerged as a new technology for drug distribution. This system is a new variation of flow-rack AS/RS that uses an operator or a single machine for storage operations, and uses a combination between the free-fall movement and a transport conveyor for retrieval operations. The main contribution of this paper is to develop an analytical model of the expected retrieval-travel time for the free-fall flow-rack under a dedicated storage assignment policy. The proposed model, which is based on a continuous approach, is compared for accuracy, via simulation, with discrete model. The obtained results show that the maximum deviation between the continuous model and the simulation is less than 5%, which shows the accuracy of our model to estimate the retrieval time. The analytical model is useful to optimise the dimensions of the rack, assess the system throughput, and evaluate different storage policies.

Factors associated with higher oxytocin requirements in labor.

PubMed

Frey, Heather A; Tuuli, Methodius G; England, Sarah K; Roehl, Kimberly A; Odibo, Anthony O; Macones, George A; Cahill, Alison G

2015-09-01

To identify clinical characteristics associated with high maximum oxytocin doses in women who achieve complete cervical dilation. A retrospective nested case-control study was performed within a cohort of all term women at a single center between 2004 and 2008 who reached the second stage of labor. Cases were defined as women who had a maximum oxytocin dose during labor >20 mu/min, while women in the control group had a maximum oxytocin dose during labor of ≤20 mu/min. Exclusion criteria included no oxytocin administration during labor, multiple gestations, major fetal anomalies, nonvertex presentation, and prior cesarean delivery. Multiple maternal, fetal, and labor factors were evaluated with univariable analysis and multivariable logistic regression. Maximum oxytocin doses >20 mu/min were administered to 108 women (3.6%), while 2864 women received doses ≤20 mu/min. Factors associated with higher maximum oxytocin dose after adjusting for relevant confounders included maternal diabetes, birthweight >4000 g, intrapartum fever, administration of magnesium, and induction of labor. Few women who achieve complete cervical dilation require high doses of oxytocin. We identified maternal, fetal and labor factors that characterize this group of parturients.

41 CFR 301-31.10 - How will my agency pay my subsistence expenses?

Code of Federal Regulations, 2011 CFR

2011-07-01

... maximum lodging amount applicable to the locality .75 times the maximum lodging amount applicable to the locality .5 times the maximum lodging amount applicable to the locality. Payment for lodging, meals, and other per diem expenses The maximum per diem rate applicable to the locality .75 times the maximum per...

Hidden Costs of Hospital Based Delivery from Two Tertiary Hospitals in Western Nepal.

PubMed

Acharya, Jeevan; Kaehler, Nils; Marahatta, Sujan Babu; Mishra, Shiva Raj; Subedi, Sudarshan; Adhikari, Bipin

2016-01-01

Hospital based delivery has been an expensive experience for poor households because of hidden costs which are usually unaccounted in hospital costs. The main aim of this study was to estimate the hidden costs of hospital based delivery and determine the factors associated with the hidden costs. A hospital based cross-sectional study was conducted among 384 post-partum mothers with their husbands/house heads during the discharge time in Manipal Teaching Hospital and Western Regional Hospital, Pokhara, Nepal. A face to face interview with each respondent was conducted using a structured questionnaire. Hidden costs were calculated based on the price rate of the market during the time of the study. The total hidden costs for normal delivery and C-section delivery were 243.4 USD (US Dollar) and 321.6 USD respectively. Of the total maternity care expenditures; higher mean expenditures were found for food & drinking (53.07%), clothes (9.8%) and transport (7.3%). For postpartum women with their husband or house head, the total mean opportunity cost of "days of work loss" were 84.1 USD and 81.9 USD for normal delivery and C-section respectively. Factors such as literate mother (p = 0.007), employed house head (p = 0.011), monthly family income more than 25,000 NRs (Nepalese Rupees) (p = 0.014), private hospital as a place of delivery (p = 0.0001), C-section as a mode of delivery (p = 0.0001), longer duration (>5days) of stay in hospital (p = 0.0001), longer distance (>15km) from house to hospital (p = 0.0001) and longer travel time (>240 minutes) from house to hospital (p = 0.007) showed a significant association with the higher hidden costs (>25000 NRs). Experiences of hidden costs on hospital based delivery and opportunity costs of days of work loss were found high. Several socio-demographic factors, delivery related factors (place and mode of delivery, length of stay, distance from hospital and travel time) were associated with hidden costs. Hidden costs can be a critical factor for many poor and remote households who attend the hospital for delivery. Current remuneration (10-15 USD for normal delivery, 30 USD for complicated delivery and 70 USD for caesarean section delivery) for maternity incentive needs to account the hidden costs by increasing it to 250 USD for normal delivery and 350 USD for C-section. Decentralization of the obstetric care to remote and under-privileged population might reduce the economic burden of pregnant women and can facilitate their attendance at the health care centers.

Receptivity of African American Adolescents to an HIV-Prevention Curriculum Enhanced by Text Messaging

PubMed Central

Cornelius, Judith B.; St Lawrence, Janet S.

2013-01-01

PURPOSE This study assessed African American adolescents’ receptivity to an HIV-prevention curriculum enhanced by text messaging. DESIGN AND METHODS Two focus groups were conducted with 14 African American adolescents regarding how an HIV-prevention curriculum could be enhanced for text messaging delivery. RESULTS The adolescents were receptive to the idea of text messaging HIV-prevention information but wanted to receive a maximum of three messages per day during the hours of 4:00–6:00 p.m. PRACTICE IMPLICATIONS By taking the findings of this study, nurses, other healthcare providers, and community-based organizations can adapt evidence-based interventions for text messaging delivery to individuals at high risk for HIV infection. PMID:19356206

Inadequacy of Plasma Acyclovir Levels at Delivery in Patients with Genital Herpes Receiving Oral Acyclovir Suppressive Therapy in Late Pregnancy

PubMed Central

Leung, Daniel T.; Henning, Paul A.; Wagner, Emily C.; Blasig, Audrey; Wald, Anna; Sacks, Stephen L.; Corey, Lawrence; Money, Deborah M.

2009-01-01

Objective: Acyclovir therapy in late pregnancy among women with recurrent genital herpes is effective in decreasing genital lesion frequency and subclinical viral shedding rates at delivery, thereby decreasing the need for caesarean delivery. Despite good adherence and increased dosing schedules, breakthrough lesions and viral shedding are still observed in some women at or near delivery. Anecdotal data suggests that low levels of HSV replication at delivery may result in transmission to the neonate. Therefore, defining optimal acyclovir dosing during labor and delivery is warranted. Our objectives were to determine actual acyclovir levels at delivery, and explore associations between acyclovir levels, duration of labour and time since last acyclovir dose. Methods: Twenty-seven patients were prescribed oral acyclovir 400 mg three times daily from 36 weeks gestation. Cord blood (venous and arterial) and maternal venous blood samples were collected at delivery, and acyclovir levels measured using capillary electrophoresis. Correlations between duration of labour and time since last acyclovir dose with acyclovir blood levels were calculated. Results: Acyclovir levels were below the published mean steady-state trough value (180 ng/ml) in 52% of venous cord, 55% of arterial cord, and 36% of maternal samples. There was a significant inverse correlation between time since last dose and venous cord (rs19=−0.57, p<0.015), arterial cord (rs16=−0.63, p<0.01), and maternal acyclovir levels (r10=−0.69, p<0.03). Conclusions: Oral dosing of acyclovir in late pregnancy may result in insufficient levels at delivery to prevent viral shedding. Alternative approaches should evaluate dosing through labor, perhaps intravenously, and its effect on viral shedding. PMID:20085679

Risk factors for cesarean section and instrumental vaginal delivery after successful external cephalic version.

PubMed

de Hundt, Marcella; Vlemmix, Floortje; Bais, Joke M J; de Groot, Christianne J; Mol, Ben Willem; Kok, Marjolein

2016-01-01

Aim of this article is to examine if we could identify factors that predict cesarean section and instrumental vaginal delivery in women who had a successful external cephalic version. We used data from a previous randomized trial among 25 hospitals and their referring midwife practices in the Netherlands. With the data of this trial, we performed a cohort study among women attempting vaginal delivery after successful ECV. We evaluated whether maternal age, gestational age, parity, time interval between ECV and delivery, birth weight, neonatal gender, and induction of labor were predictive for a vaginal delivery on one hand or a CS or instrumental vaginal delivery on the other hand. Unadjusted and adjusted odds ratios were calculated with univariate and multivariate logistic regression analysis. Among 301 women who attempted vaginal delivery after a successful external cephalic version attempt, the cesarean section rate was 13% and the instrumental vaginal delivery rate 6%, resulting in a combined instrumental delivery rate of 19%. Nulliparity increased the risk of cesarean section (OR 2.7 (95% CI 1.2-6.1)) and instrumental delivery (OR 4.2 (95% CI 2.1-8.6)). Maternal age, gestational age at delivery, time interval between external cephalic version and delivery, birth weight and neonatal gender did not contribute to the prediction of failed spontaneous vaginal delivery. In our cohort of 301 women with a successful external cephalic version, nulliparity was the only one of seven factors that predicted the risk for cesarean section and instrumental vaginal delivery.

Characterization of Chlorhexidine-Loaded Calcium-Hydroxide Microparticles as a Potential Dental Pulp-Capping Material

PubMed Central

Priyadarshini, Balasankar M.; Selvan, Subramanian T.; Narayanan, Karthikeyan; Fawzy, Amr S.

2017-01-01

This study explores the delivery of novel calcium hydroxide [Ca(OH)2] microparticles loaded with chlorhexidine (CHX) for potential dental therapeutic and preventive applications. Herein, we introduce a new approach for drug-delivery to deep dentin-surfaces in the form of drug-loaded microparticles. Unloaded Ca(OH)2 [Ca(OH)2/Blank] and CHX-loaded/Ca(OH)2 microparticles were fabricated by aqueous chemical-precipitation technique. The synthesized-microparticles were characterized in vitro for determination of surface-morphology, crystalline-features and thermal-properties examined by energy-dispersive X-ray scanning and transmission electron-microscopy (EDX-SEM/TEM), Fourier-transform infrared-spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA) and differential scanning-calorimetry (DSC). Time-related pH changes, initial antibacterial/biofilm-abilities and cytotoxicity of CHX-loaded/Ca(OH)2 microparticles were evaluated. Microparticles were delivered to dentin-surfaces with subsequent SEM examination of treated dentin-substrates. The in vitro and ex vivo CHX-release profiles were characterized. Ca(OH)2/Blank were hexagonal-shaped with highest z-average diameter whereas CHX-inclusion evidenced micro-metric spheres with distinguishable surface “rounded deposits” and a negative-shift in diameter. CHX:Ca(OH)2/50 mg exhibited maximum encapsulation-efficiency with good antibacterial and cytocompatible properties. SEM examination revealed an intact layer of microparticles on exposed dentin-surfaces with retention of spherical shape and smooth texture. Microparticles loaded on dentin-surfaces showed prolonged release of CHX indicating substantial retention on dentin-substrates. This study validated the inherent-applicability of this novel drug-delivery approach to dentin-surfaces using micro-metric CHX-loaded/Ca(OH)2 microparticles. PMID:28952538

Development of a Transnasal Delivery System for Recombinant Human Growth Hormone (rhGH): Effects of the Concentration and Molecular Weight of Poly-L-arginine on the Nasal Absorption of rhGH in Rats.

PubMed

Kawashima, Ryo; Uchida, Masaki; Yamaki, Tsutomu; Ohtake, Kazuo; Hatanaka, Tomomi; Uchida, Hiroyuki; Ueda, Hideo; Kobayashi, Jun; Morimoto, Yasunori; Natsume, Hideshi

2016-01-01

A novel system for delivering recombinant human growth hormone (rhGH) that is noninvasive and has a simple method of administration is strongly desired to improve the compliance of children. The aim of this study was to investigate the potential for the intranasal (i.n.) co-administration of rhGH with poly-L-arginine (PLA) as a novel delivery system by evaluating the effects of the concentration and molecular weight of PLA on the nasal absorption of rhGH. The influence of the formation of insoluble aggregates and a soluble complex in the dosage formulation on nasal rhGH absorption was also evaluated by size-exclusion chromatography and ultrafiltration. PLA enhanced the nasal absorption of rhGH at each concentration and molecular weight examined. Nasal rhGH absorption increased dramatically when the PLA concentration was 1.0 % (w/v) due to the improved solubility of rhGH in the formulation. A delay in rhGH absorption was observed when the molecular weight of PLA was increased. This appeared to be because the increase in molecular weight caused the formation of a soluble complex. It seems that the PLA concentration affects the absorption-enhancing effect on rhGH, while the molecular weight of PLA affects the time when the maximum plasma rhGH concentration was reached (Tmax) of rhGH after i.n. administration, mainly because of the interactions among rhGH, PLA, and additives. Therefore, the transnasal rhGH delivery system using PLA is considered to be a promising alternative to subcutaneous (s.c.) injection if these interactions are sufficiently controlled.

Gestational diabetes and risk of cardiovascular disease up to 25 years after pregnancy: a retrospective cohort study.

PubMed

McKenzie-Sampson, Safyer; Paradis, Gilles; Healy-Profitós, Jessica; St-Pierre, Frédérique; Auger, Nathalie

2018-04-01

The risk of cardiovascular disease in women with gestational diabetes is poorly understood. We sought to determine whether gestational diabetes increases the risk of cardiovascular disease more than two decades after pregnancy. We carried out a retrospective cohort study of 1,070,667 women who delivered infants in hospitals within Quebec, Canada, between 1989 and 2013. We followed 67,356 women with gestational diabetes and 1,003,311 without gestational diabetes for a maximum of 25.2 years after the index delivery. The main outcome measures were hospitalization for ischemic heart disease, myocardial infarction, coronary angioplasty, coronary artery bypass graft, and other cardiovascular disorders. We used Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) comparing women with gestational diabetes to no gestational diabetes, adjusted for age, parity, socioeconomic deprivation, time period, and preeclampsia. Women with gestational diabetes had a higher cumulative incidence of hospitalization for cardiovascular disease 25 years after delivery (190.8 per 1000 women) compared with no gestational diabetes (117.8 per 1000 women). Gestational diabetes was associated with a higher risk of ischemic heart disease (HR 1.23, 95% CI 1.12-1.36), myocardial infarction (HR 2.14, 95% CI 1.15-2.47), coronary angioplasty (HR 2.23, 95% CI 1.87-2.65), and coronary artery bypass graft (HR 3.16, 95% CI 2.24-4.47). In this population of pregnant women, gestational diabetes was associated with an increased risk of heart disease 25 years after delivery. Women with gestational diabetes may merit closer monitoring for cardiovascular disease prevention after pregnancy.

Intranasal haloperidol-loaded miniemulsions for brain targeting: Evaluation of locomotor suppression and in-vivo biodistribution.

PubMed

El-Setouhy, Doaa Ahmed; Ibrahim, A B; Amin, Maha M; Khowessah, Omneya M; Elzanfaly, Eman S

2016-09-20

Haloperidol is a commonly prescribed antipsychotic drug currently administered as oral and injectable preparations. This study aimed to prepare haloperidol intranasal miniemulsion helpful for psychiatric emergencies and exhibiting lower systemic exposure and side effects associated with non-target site delivery. Haloperidol miniemulsions were successfully prepared by spontaneous emulsification adopting 2(3) factorial design. The effect of three independent variables at two levels each namely; oil type (Capmul®-Capryol™90), lipophilic emulsifier type (Span 20-Span 80) and HLB value (12-14) on globule size, PDI and percent locomotor activity inhibition in mice was evaluated. The optimized formula (F4, Capmul®, Tween 80/Span 20, HLB 14) showed globule size of 209.5±0.98nm, PDI of 0.402±0.03 and locomotor inhibition of 83.89±9.15% with desirability of 0.907. Biodistribution study following intranasal and intravenous administration of the radiolabeled (99m)Tc mucoadhesive F4 revealed that intranasal administration achieved 1.72-fold higher and 6 times faster peak brain levels compared with intravenous administration. Drug targeting efficiency percent and brain/blood exposure ratios remained above 100% and 1 respectively after intranasal instillation compared to a maximum brain/blood exposure ratio of 0.8 post intravenous route. Results suggested the CNS delivery of major fraction of haloperidol via direct transnasal to brain pathway that can be a promising alternative to oral and parenteral routes in chronic and acute situations. Haloperidol concentration of 275.6ng/g brain 8h post intranasal instillation, higher than therapeutic concentration range of haloperidol (0.8 to 5.15ng/ml), suggests possible sustained delivery of the drug through nasal route. Copyright © 2016 Elsevier B.V. All rights reserved.

Treatment of Parkinson’s disease: nanostructured sol–gel silica–dopamine reservoirs for controlled drug release in the central nervous system

PubMed Central

López, Tessy; Bata-García, José L; Esquivel, Dulce; Ortiz-Islas, Emma; Gonzalez, Richard; Ascencio, Jorge; Quintana, Patricia; Oskam, Gerko; Álvarez-Cervera, Fernando J; Heredia-López, Francisco J; Góngora-Alfaro, José L

2011-01-01

Introduction We have evaluated the use of silica–dopamine reservoirs synthesized by the sol–gel approach with the aim of using them in the treatment of Parkinson’s disease, specifically as a device for the controlled release of dopamine in the striatum. Theoretical calculations illustrate that dopamine is expected to assume a planar structure and exhibit weak interactions with the silica surface. Methods Several samples were prepared by varying the wt% of dopamine added during the hydrolysis of tetraethyl orthosilicate. The silica–dopamine reservoirs were characterized by N2 adsorption, scanning and transmission electron microscopy, and Fourier transform infrared spectroscopy. The in vitro release profiles were determined using ultraviolet visible absorbance spectroscopy. The textural analyses showed a maximum value for the surface area of 620 m2/g nanostructured silica materials. The stability of dopamine in the silica network was confirmed by infrared and 13C-nuclear magnetic resonance spectroscopy. The reservoirs were evaluated by means of apomorphine-induced rotation behavior in hemiparkisonian rats. Results The in vitro dopamine delivery profiles indicate two regimes of release, a fast and sustained dopamine delivery was observed up to 24 hours, and after this time the rate of delivery became constant. Histologic analysis of formalin-fixed brains performed 24–32 weeks after reservoir implantation revealed that silica–dopamine implants had a reddish-brown color, suggesting the presence of oxidized dopamine, likely caused by the fixation procedure, while implants without dopamine were always translucent. Conclusion The major finding of the study was that intrastriatal silica–dopamine implants reversed the rotational asymmetry induced by apomorphine, a dopamine agonist, in hemiparkinsonian rats. No dyskinesias or other motor abnormalities were observed in animals implanted with silica or silica–dopamine. PMID:21289978

Breast conserving treatment for breast cancer: dosimetric comparison of different non-invasive techniques for additional boost delivery

PubMed Central

2014-01-01

Background Today it is unclear which technique for delivery of an additional boost after whole breast radiotherapy for breast conserved patients should be state of the art. We present a dosimetric comparison of different non-invasive treatment techniques for additional boost delivery. Methods For 10 different tumor bed localizations, 7 different non-invasive treatment plans were made. Dosimetric comparison of PTV-coverage and dose to organs at risk was performed. Results The Vero system achieved an excellent PTV-coverage and at the same time could minimize the dose to the organs at risk with an average near-maximum-dose (D2) to the heart of 0.9 Gy and the average volume of ipsilateral lung receiving 5 Gy (V5) of 1.5%. The TomoTherapy modalities delivered an average D2 to the heart of 0.9 Gy for the rotational and of 2.3 Gy for the static modality and an average V5 to the ipsilateral lung of 7.3% and 2.9% respectively. A rotational technique offers an adequate conformity at the cost of more low dose spread and a larger build-up area. In most cases a 2-field technique showed acceptable PTV-coverage, but a bad conformity. Electrons often delivered a worse PTV-coverage than photons, with the planning requirements achieved only in 2 patients and with an average D2 to the heart of 2.8 Gy and an average V5 to the ipsilateral lung of 5.8%. Conclusions We present advices which can be used as guidelines for the selection of the best individualized treatment. PMID:24467916

Intermediate variables as determinants of adverse pregnancy outcome in high-risk inner-city populations.

PubMed

Sharma, R; Synkewecz, C; Raggio, T; Mattison, D R

1994-11-01

A probability sample survey of high-risk inner-city women with a live birth in the last 3 years shows that maternal medical risks and health behaviors during pregnancy are important intermediate variables influencing preterm delivery and birthweight. Women who developed two or more medical risks had about three-and-a-half times the risk of preterm delivery and two-and-a-half times the risk of low birthweight compared to those without such risks. Women with prior fetal loss had twofold increase in the risk of preterm delivery and low birthweight. Unintended pregnancy resulted in one-and-a-half to twofold increase in preterm delivery and low birthweight, respectively. Inadequate gestational weight increased the risk of preterm delivery by about 50%. Smoking during pregnancy raised the risk of low birthweight slightly more than one-and-a-half times.

How Guilds Build Success; Aspects of Temporal Resource Partitioning in a Warm, Temperate Climate Assemblage of Dung Beetles (Coleoptera: Scarabaeidae).

PubMed

Sullivan, Gregory T; Ozman-Sullivan, Sebahat K; Lumaret, Jean-Pierre; Bourne, Anne; Zeybekoglu, Unal; Zalucki, Myron P; Baxter, Greg

2017-10-01

Succession in local dung beetle assemblages influences their delivery of ecological functions in natural and modified environments globally. Short-term changes in dung beetle (Coleoptera: Scarabaeidae) species richness, abundance, and biomass were investigated in standardized dung pads in northern, coastal Turkey. For mean tunneling guild abundance, dung deposition time, dung exposure period, and their interaction were significant, and for mean dung dwelling guild abundance, dung exposure period was significant, as was the interaction with dung deposition time, which collectively evidenced temporal resource partitioning, based principally on differences in diel activity. Succession was highly compressed, with maximum abundance at 12 h and maximum species richness at 24 h. A large ball roller and small- to medium-sized tunnelers dominated different periods in the first 24 h but were superseded by dwellers. Regression analysis demonstrated a significant, positive relationship between species richness and the evenness of abundance for both dung deposition times. Correlation analysis generally showed strong, positive correlations between tunneling species, low correlations between tunneling and dwelling species, and low correlations between dwelling species. Niche partitioning based on size difference appears to have acted on the environmental filtering of tunneling species along the temporal gradient of declining moisture, thereby limiting the number of abundant, concurrent species. The aggregation of tunneling species provided opportunities for the less competitive dwelling species to occupy less densely populated zones termed probability refuges. The network of strong, positive habitat' correlations between tunneling species may indicate that their collective functionality is vulnerable to loss of efficiency if species are lost. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A flexible electrostatic kinetic energy harvester based on electret films of electrospun nanofibers

NASA Astrophysics Data System (ADS)

Lu, Y.; Capo-Chichi, M.; Leprince-Wang, Y.; Basset, P.

2018-01-01

This paper reports a paper-based electrostatic kinetic energy harvester (e-KEH) implementing multilayered electret films based on electrospun nanofibrous material. It is the first time that a fully flexible electret-based e-KEH is reported. The proposed electret, PVDF-PTFD nanofibrous covered by Parylene C, has a faster stabilization of surface potential than a planar thin film of Parylene C, and a higher stability of charge storage. With a maximum force of 0.5 N and a 3-layer electret, the device capacitance increases from 25 to 100 pF during a pressing operation. Working with the optimal resistive load of 16 MΩ, the device pressed manually delivers a peak instantaneous power up to 45.6 μW and an average energy of 54 nJ/stroke, corresponding to a peak instantaneous power density of 7.3 μW cm-2 and an average energy density of 8.6 nJ cm-2/stroke. Within 450 manual strokes, a 10 nF capacitor is charged up to 8.5 V by the prototype through a full-wave diode bridge. On a 1 μF capacitor, the energy delivery of 9.9 nJ/stroke has been obtained with a 10 Hz pressing movement excited by a vibrator with a maximum force of 0.5 N.

Insulin delivery device technology 2012: where are we after 90 years?

PubMed

Fry, Andrew

2012-07-01

Since the first successful use of insulin in 1921 to treat diabetes at Toronto General Hospital, the major advances in development of the medication itself have taken place in parallel with equally significant developments in the means of delivery. Administration of insulin remains parenteral. This article reviews the main variants in prescription-available delivery technology: vial and syringe, pen injector, needle-free injection, and continuous subcutaneous insulin infusion pumps. For each of these, the background and major milestones are covered briefly and followed by a discussion of the latest product innovations, technologies, and implementations, which are all considered in the context of the interaction with users. The article concludes by reflecting upon how the progress in the technology of diabetes management can best serve the patient. The spectacular technological advances in medication, monitoring, and delivery since 1922 have transformed the lives of millions. However, the fact that we can add sophisticated technology to delivery devices and accessories does not mean it is always the best thing for the patient. Electronic sophistication may be welcomed by a young, eager type 1 diabetes patient, while a senior citizen who discovers he has type 2 diabetes may yearn for simplicity. Technology continues to provide great solutions, but the type of solution delivered must be matched to the user if the maximum benefit is to be achieved for all. © 2012 Diabetes Technology Society.

Insulin Delivery Device Technology 2012: Where Are We after 90 Years?

PubMed Central

Fry, Andrew

2012-01-01

Since the first successful use of insulin in 1921 to treat diabetes at Toronto General Hospital, the major advances in development of the medication itself have taken place in parallel with equally significant developments in the means of delivery. Administration of insulin remains parenteral. This article reviews the main variants in prescription-available delivery technology: vial and syringe, pen injector, needle-free injection, and continuous subcutaneous insulin infusion pumps. For each of these, the background and major milestones are covered briefly and followed by a discussion of the latest product innovations, technologies, and implementations, which are all considered in the context of the interaction with users. The article concludes by reflecting upon how the progress in the technology of diabetes management can best serve the patient. The spectacular technological advances in medication, monitoring, and delivery since 1922 have transformed the lives of millions. However, the fact that we can add sophisticated technology to delivery devices and accessories does not mean it is always the best thing for the patient. Electronic sophistication may be welcomed by a young, eager type 1 diabetes patient, while a senior citizen who discovers he has type 2 diabetes may yearn for simplicity. Technology continues to provide great solutions, but the type of solution delivered must be matched to the user if the maximum benefit is to be achieved for all. PMID:22920823

Do time of birth, unit volume, and staff seniority affect neonatal outcome in deliveries at ≥34+0 weeks of gestation?

PubMed

Reif, P; Pichler, G; Griesbacher, A; Lehner, G; Schöll, W; Lang, U; Hofmann, H; Ulrich, D

2018-06-01

We investigated whether time of birth, unit volume, and staff seniority affect neonatal outcome in neonates born at ≥34 +0 weeks of gestation. Population-based prospective cohort study. Ten public hospitals in the Austrian province of Styria. A total of 87 065 neonates delivered in the period 2004-2015. Based on short-term outcome data, generalised linear mixed models were used to calculate the risk for adverse and severely adverse neonatal outcomes according to time of birth, unit volume, and staff seniority. Neonatal composite adverse and severely adverse outcome measures. The odds ratio for severely adverse events during the night-time (22:01-07:29 hours) compared with the daytime (07:30-15:00 hours) was 1.35 (95% confidence interval, 95% CI 1.13-1.61). There were no significant differences in neonatal outcome comparing weekdays and weekends, and comparing office hours and shifts. Units with 500-1000 deliveries per year had the lowest risk for adverse events. Adverse and severely adverse neonatal outcomes were least common for midwife-guided deliveries, and became more frequent with the level of experience of the doctors attending the delivery. With increasing pregnancy risks, senior staff attending delivery and delivering in a tertiary centre reduce the odds ratio for adverse events. Different times of delivery were associated with increased adverse neonatal outcomes. The management of uncomplicated deliveries by less experienced staff showed no negative impact on perinatal outcome. In contrast, riskier pregnancies delivered by senior staff in a tertiary centre favour a better outcome. Achieving a better balance in the total number of labour ward staff during the day and the night appears to be a greater priority than increasing the continuous presence of senior obstetrical staff on the labour ward during the out-of-hours period. Deliveries during night time lead to a greater number of neonates experiencing severely adverse events. © 2017 Royal College of Obstetricians and Gynaecologists.

Management of three-dimensional intrafraction motion through real-time DMLC tracking.

PubMed

Sawant, Amit; Venkat, Raghu; Srivastava, Vikram; Carlson, David; Povzner, Sergey; Cattell, Herb; Keall, Paul

2008-05-01

Tumor tracking using a dynamic multileaf collimator (DMLC) represents a promising approach for intrafraction motion management in thoracic and abdominal cancer radiotherapy. In this work, we develop, empirically demonstrate, and characterize a novel 3D tracking algorithm for real-time, conformal, intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT)-based radiation delivery to targets moving in three dimensions. The algorithm obtains real-time information of target location from an independent position monitoring system and dynamically calculates MLC leaf positions to account for changes in target position. Initial studies were performed to evaluate the geometric accuracy of DMLC tracking of 3D target motion. In addition, dosimetric studies were performed on a clinical linac to evaluate the impact of real-time DMLC tracking for conformal, step-and-shoot (S-IMRT), dynamic (D-IMRT), and VMAT deliveries to a moving target. The efficiency of conformal and IMRT delivery in the presence of tracking was determined. Results show that submillimeter geometric accuracy in all three dimensions is achievable with DMLC tracking. Significant dosimetric improvements were observed in the presence of tracking for conformal and IMRT deliveries to moving targets. A gamma index evaluation with a 3%-3 mm criterion showed that deliveries without DMLC tracking exhibit between 1.7 (S-IMRT) and 4.8 (D-IMRT) times more dose points that fail the evaluation compared to corresponding deliveries with tracking. The efficiency of IMRT delivery, as measured in the lab, was observed to be significantly lower in case of tracking target motion perpendicular to MLC leaf travel compared to motion parallel to leaf travel. Nevertheless, these early results indicate that accurate, real-time DMLC tracking of 3D tumor motion is feasible and can potentially result in significant geometric and dosimetric advantages leading to more effective management of intrafraction motion.

SU-E-J-150: Impact of Intrafractional Prostate Motion On the Accuracy and Efficiency of Prostate SBRT Delivery: A Retrospective Analysis of Prostate Tracking Log Files

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

Xiang, H; Hirsch, A; Willins, J

2014-06-01

Purpose: To measure intrafractional prostate motion by time-based stereotactic x-ray imaging and investigate the impact on the accuracy and efficiency of prostate SBRT delivery. Methods: Prostate tracking log files with 1,892 x-ray image registrations from 18 SBRT fractions for 6 patients were retrospectively analyzed. Patient setup and beam delivery sessions were reviewed to identify extended periods of large prostate motion that caused delays in setup or interruptions in beam delivery. The 6D prostate motions were compared to the clinically used PTV margin of 3–5 mm (3 mm posterior, 5 mm all other directions), a hypothetical PTV margin of 2–3 mmmore » (2 mm posterior, 3 mm all other directions), and the rotation correction limits (roll ±2°, pitch ±5° and yaw ±3°) of CyberKnife to quantify beam delivery accuracy. Results: Significant incidents of treatment start delay and beam delivery interruption were observed, mostly related to large pitch rotations of ≥±5°. Optimal setup time of 5–15 minutes was recorded in 61% of the fractions, and optimal beam delivery time of 30–40 minutes in 67% of the fractions. At a default imaging interval of 15 seconds, the percentage of prostate motion beyond PTV margin of 3–5 mm varied among patients, with a mean at 12.8% (range 0.0%–31.1%); and the percentage beyond PTV margin of 2–3 mm was at a mean of 36.0% (range 3.3%–83.1%). These timely detected offsets were all corrected real-time by the robotic manipulator or by operator intervention at the time of treatment interruptions. Conclusion: The durations of patient setup and beam delivery were directly affected by the occurrence of large prostate motion. Frequent imaging of down to 15 second interval is necessary for certain patients. Techniques for reducing prostate motion, such as using endorectal balloon, can be considered to assure consistently higher accuracy and efficiency of prostate SBRT delivery.« less

42 CFR 457.555 - Maximum allowable cost-sharing charges on targeted low-income children in families with income...

Code of Federal Regulations, 2011 CFR

2011-10-01

... requirements must be met: (1)(i) For Federal FY 2009, any co-payment or similar charge the State imposes under a fee-for-service delivery system may not exceed the amounts shown in the following table: State...) For Federal FY 2009, any co-payment that the State imposes for services provided by a managed care...

42 CFR 457.555 - Maximum allowable cost-sharing charges on targeted low-income children in families with income...

Code of Federal Regulations, 2010 CFR

2010-10-01

... requirements must be met: (1)(i) For Federal FY 2009, any co-payment or similar charge the State imposes under a fee-for-service delivery system may not exceed the amounts shown in the following table: State...) For Federal FY 2009, any co-payment that the State imposes for services provided by a managed care...

Design and Evaluation for the End-to-End Detection of TCP/IP Header Manipulation

DTIC Science & Technology

2014-06-01

Cooperative Association for Internet Data Analysis CDN content delivery network CE congestion encountered CRC cyclic redundancy check CWR congestion...Switzerland was primarily developed as a network neutrality analysis tool to detect when internet service providers (ISPs) were interfering with...maximum 200 words) Understanding, measuring, and debugging IP networks , particularly across administrative domains, is challenging. One aspect of the

Dosimetric evaluation of total marrow irradiation using 2 different planning systems

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

Nalichowski, Adrian, E-mail: nalichoa@karmanos.org; Eagle, Don G.; Burmeister, Jay

This study compared 2 different treatment planning systems (TPSs) for quality and efficiency of total marrow irradiation (TMI) plans. The TPSs used in this study were VOxel-Less Optimization (VoLO) (Accuray Inc, Sunnyvale, CA) using helical dose delivery on a Tomotherapy Hi-Art treatment unit and Eclipse (Varian Medical Systems Inc, Palo Alto, CA) using volumetric modulated arc therapy (VMAT) dose delivery on a Varian iX treatment unit. A total dose of 1200 cGy was prescribed to cover 95% of the planning target volume (PTV). The plans were optimized and calculated based on a single CT data and structure set using themore » Alderson Rando phantom (The Phantom Laboratory, Salem, NY) and physician contoured target and organ at risk (OAR) volumes. The OARs were lungs, heart, liver, kidneys, brain, and small bowel. The plans were evaluated based on plan quality, time to optimize the plan and calculate the dose, and beam on time. The resulting mean and maximum doses to the PTV were 1268 and 1465 cGy for VoLO and 1284 and 1541 cGy for Eclipse, respectively. For 5 of 6 OAR structures the VoLO system achieved lower mean and D10 doses ranging from 22% to 52% and 3% to 44%, respectively. Total computational time including only optimization and dose calculation were 0.9 hours for VoLO and 3.8 hours for Eclipse. These times do not include user-dependent target delineation and field setup. Both planning systems are capable of creating high-quality plans for total marrow irradiation. The VoLO planning system was able to achieve more uniform dose distribution throughout the target volume and steeper dose fall off, resulting in superior OAR sparing. VoLO's graphics processing unit (GPU)–based optimization and dose calculation algorithm also allowed much faster creation of TMI plans.« less

High-speed graphene@Ag-MnO2 micromotors at low peroxide levels.

PubMed

Ye, Heng; Kang, Jian; Ma, Guofeng; Sun, Hongqi; Wang, Shaobin

2018-05-25

Platinum (Pt) free micro/nanomotors (MNMs) using a low content of fuels are highly desired for many applications. Herein, we demonstrate that cathodic electrofabrication can produce modified MnO 2 based microtubes and microrods as highly efficient MNMs in hydrogen peroxide (H 2 O 2 ) as low as 0.2%. The speed of graphene/Ag-MnO 2 micromotors could be smartly regulated using a surfactant and the maximum speed of an individual micromotor exceeds 1.3 mm s -1 in 0.5% H 2 O 2 . The propelling force and output power of the micromotors are 3.4 and 10 times as high as those of the best Pt-based micromotors reported. These Ag-MnO 2 based micromotors are envisioned to be a great promise for practical applications from biomedical delivery to environmental decontamination. Copyright © 2018 Elsevier Inc. All rights reserved.

Cross-Country Skiing Injuries and Training Methods.

PubMed

Nagle, Kyle B

2015-01-01

Cross-country skiing is a low injury-risk sport that has many health benefits and few long-term health risks. Some concern exists that cross-country skiing may be associated with a higher incidence of atrial fibrillation; however, mortality rates among skiers are lower than those among the general population. While continuing to emphasize aerobic and anaerobic training, training methods also should promote ski-specific strength training to increase maximum force and its rate of delivery and to build muscular endurance to maintain that power through a race. Multiple tests are available to monitor training progress. Which tests are most appropriate depends on the specific events targeted. In addition to laboratory-based tests, there also are many simpler, more cost-effective tests, such as short time trials, that can be used to monitor training progress and predict performance particularly at the junior skier level where access and cost may be more prohibitive.

Spatiotemporal predictability of schooling and nonschooling prey of Pigeon Guillemots

USGS Publications Warehouse

Litzow, Michael A.; Piatt, John F.; Abookire, Alisa A.; Speckman, Suzann G.; Arimitsu, Mayumi L.; Figurski, Jared D.

2004-01-01

Low spatiotemporal variability in the abundance of nonschooling prey might allow Pigeon Guillemots (Cepphus columba) to maintain the high chick provisioning rates that are characteristic of the species. We tested predictions of this hypothesis with data collected with beach seines and scuba and hydroacoustic surveys in Kachemak Bay, Alaska, during 1996–1999. Coefficients of variability were 20–211% greater for schooling than nonschooling prey on day, seasonal, and km scales. However, the proportion of schooling prey in chick diets explained relatively little variability in Pigeon Guillemot meal delivery rates at the scale of hours (r2 = 0.07) and weeks (r2 = 0.19). Behavioral adaptations such as flexible time budgets likely ameliorate the negative effects of high resource variability, but we propose that these adaptations are only effective when schooling prey are available at distances well below the maximum foraging range of the species.

Biophysical considerations for optimizing energy delivery during Erbium:YAG laser vitreoretinal surgery

NASA Astrophysics Data System (ADS)

Berger, Jeffrey W.; Bochow, Thomas W.; Kim, Rosa Y.; D'Amico, Donald J.

1996-05-01

Er:YAG laser-mediated tissue disruption and removal results from both direct ablation and the acousto-mechanical sequelae of explosive vaporization of the tissue water. We investigated the scaling laws for photoablative and photodisruptive interactions, and interpret these results towards optimizing energy delivery for vitreoretinal surgical maneuvers. Experimental studies were performed with a free-running Er:YAG laser (100 - 300 microseconds FWHM, 0.5 - 20 mJ, 1 - 30 Hz). Energy was delivered by fiberoptic to a custom-made handpiece with a 75 - 600 micrometer quartz tip, and applied to excised, en bloc samples of bovine vitreous or model systems of saline solution. Sample temperature was measured with 33 gauge copper- constantan thermocouples. Expansion and collapse of the bubble following explosive vaporization of tissue water was optically detected. The bubble size was calculated from the period of the bubble oscillation and known material properties. A model for bubble expansion is presented based on energy principles and adiabatic gas expansion. Pressure transients associated with bubble dynamics are estimated following available experimental and analytical data. The temperature rise in vitreous and model systems depends on the pulse energy and repetition rate, but is independent of the probe-tip diameter at constant laser power; at moderate repetition rates, the temperature rise depends only on the total energy (mJ) delivered. The maximum bubble diameter increases as the cube root of the pulse energy with a reverberation period of 110 microseconds and a maximum bubble diameter of 1.2 mm following one mJ delivery to saline through a 100 micrometer tip. Our modeling studies generate predictions similar to experimental data and predicts that the maximum bubble diameter increases as the cube root of the pulse energy. We demonstrate that tissue ablation depends on radiant exposure (J/cm2), while temperature rise, bubble size, and pressure depends on total pulse energy. Further, we show that mechanical injury should be minimized by delivering low pulse energy, through small diameter probe tips, at high repetition rates. These results allow for optimization strategies relevant to achieving vitreoretinal surgical goals while minimizing the potential for unintentional injury.

Survey on Monitoring and Quality Controlling of the Mobile Biosignal Delivery.

PubMed

Pawar, Pravin A; Edla, Damodar R; Edoh, Thierry; Shinde, Vijay; van Beijnum, Bert-Jan

2017-10-31

A Mobile Patient Monitoring System (MPMS) acquires patient's biosignals and transmits them using wireless network connection to the decision-making module or healthcare professional for the assessment of patient's condition. A variety of wireless network technologies such as wireless personal area networks (e.g., Bluetooth), mobile ad-hoc networks (MANET), and infrastructure-based networks (e.g., WLAN and cellular networks) are in practice for biosignals delivery. The wireless network quality-of-service (QoS) requirements of biosignals delivery are mainly specified in terms of required bandwidth, acceptable delay, and tolerable error rate. An important research challenge in the MPMS is how to satisfy QoS requirements of biosignals delivery in the environment characterized by patient mobility, deployment of multiple wireless network technologies, and variable QoS characteristics of the wireless networks. QoS requirements are mainly application specific, while available QoS is largely dependent on QoS provided by wireless network in use. QoS provisioning refers to providing support for improving QoS experience of networked applications. In resource poor conditions, application adaptation may also be required to make maximum use of available wireless network QoS. This survey paper presents a survey of recent developments in the area of QoS provisioning for MPMS. In particular, our contributions are as follows: (1) overview of wireless networks and network QoS requirements of biosignals delivery; (2) survey of wireless networks' QoS performance evaluation for the transmission of biosignals; and (3) survey of QoS provisioning mechanisms for biosignals delivery in MPMS. We also propose integrating end-to-end QoS monitoring and QoS provisioning strategies in a mobile patient monitoring system infrastructure to support optimal delivery of biosignals to the healthcare professionals.

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,…

10 CFR 626.8 - Deferrals of contractually scheduled deliveries.

Code of Federal Regulations, 2011 CFR

2011-01-01

... PETROLEUM FOR THE STRATEGIC PETROLEUM RESERVE § 626.8 Deferrals of contractually scheduled deliveries. (a) General. (1) DOE prefers to take deliveries of petroleum for the SPR at times scheduled under applicable...

10 CFR 626.8 - Deferrals of contractually scheduled deliveries.

Code of Federal Regulations, 2010 CFR

2010-01-01

... PETROLEUM FOR THE STRATEGIC PETROLEUM RESERVE § 626.8 Deferrals of contractually scheduled deliveries. (a) General. (1) DOE prefers to take deliveries of petroleum for the SPR at times scheduled under applicable...

Childbirth after pelvic floor surgery: analysis of Hospital Episode Statistics in England, 2002-2008.

PubMed

Pradhan, A; Tincello, D G; Kearney, R

2013-01-01

To report the numbers of patients having childbirth after pelvic floor surgery in England. Retrospective analysis of Hospital Episode Statistics data. Hospital Episode Statistics database. Women, aged 20-44 years, undergoing childbirth after pelvic floor surgery between the years 2002 and 2008. Analysis of the Hospital Episode Statistics database using Office of Population, Censuses and Surveys: Classification of Interventions and Procedures, 4th Revision (OPCS-4) code at the four-character level for pelvic floor surgery and delivery, in women aged 20-44 years, between the years 2002 and 2008. Numbers of women having delivery episodes after previous pelvic floor surgery, and numbers having further pelvic floor surgery after delivery. Six hundred and three women had a delivery episode after previous pelvic floor surgery in the time period 2002-2008. In this group of 603 women, 42 had a further pelvic floor surgery episode following delivery in the same time period. The incidence of repeat surgery episode following delivery was higher in the group delivered vaginally than in those delivered by caesarean (13.6 versus 4.4%; odds ratio, 3.38; 95% confidence interval, 1.87-6.10). There were 603 women having childbirth after pelvic floor surgery in the time period 2002-2008. The incidence of further pelvic floor surgery after childbirth was lower after caesarean delivery than after vaginal delivery, and this may indicate a protective effect of abdominal delivery. © 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.

VMAT testing for an Elekta accelerator

PubMed Central

Sweeney, Larry E.; Marshall, Edward I.; Mahendra, Saikanth

2012-01-01

Volumetric‐modulated arc therapy (VMAT) has been shown to be able to deliver plans equivalent to intensity‐modulated radiation therapy (IMRT) in a fraction of the treatment time. This improvement is important for patient immobilization/ localization compliance due to comfort and treatment duration, as well as patient throughput. Previous authors have suggested commissioning methods for this modality. Here, we extend the methods reported for the Varian RapidArc system (which tested individual system components) to the Elekta linear accelerator, using custom files built using the Elekta iComCAT software. We also extend the method reported for VMAT commissioning of the Elekta accelerator by verifying maximum values of parameters (gantry speed, multileaf collimator (MLC) speed, and backup jaw speed), investigating: 1) beam profiles as a function of dose rate during an arc, 2) over/under dosing due to MLC reversals, and 3) over/under dosing at changing dose rate junctions. Equations for construction of the iComCAT files are given. Results indicate that the beam profile for lower dose rates varies less than 3% from that of the maximum dose rate, with no difference during an arc. The gantry, MLC, and backup jaw maximum speed are internally consistent. The monitor unit chamber is stable over the MUs and gantry movement conditions expected. MLC movement and position during VMAT delivery are within IMRT tolerances. Dose rate, gantry speed, and MLC speed are accurately controlled. Over/under dosing at junctions of MLC reversals or dose rate changes are within clinical acceptability. PACS numbers: 87.55.de, 87.55.Qr, 87.56.bd PMID:22402389

Study on laser-assisted drug delivery with optical coherence tomography

NASA Astrophysics Data System (ADS)

Tsai, Wen-Guei; Tsai, Ting-Yen; Yang, Chih-Hsun; Tsai, Meng-Tsan

2017-04-01

The nail provides a functional protection to the fingertips and surrounding tissue from external injuries. Nail plate divided into three layers including dorsal, intermediate, and ventral layers. The dorsal layer consists of compact, hard keratins, limiting topical drug delivery through the nail. In this study, we investigate the application of fractional CO2 laser that produces arrays of microthermal ablation zones (MAZs) to facilitate drug delivery in the nails. Moreover, optical coherence tomography (OCT) is implemented for real-time monitoring of the laser-skin tissue interaction, sparing the patient from invasive surgical sampling procedure. Observations of drug diffusion through the induced MAZ array are achieved by evaluating the time-dependent OCT intensity variance. Subsequently, nails are treated with cream and liquid topical drugs to investigate the feasibility and diffusion efficacy of laser-assisted drug delivery. Our results show that fractional CO2 laser improves the efficacy of topical drug delivery in the nail plate, and that OCT could potentially be used for in vivo monitoring of the depth of laser penetration as well as real-time observations of drug delivery.

Cascading of Fluctuations in Interdependent Energy Infrastructures. Gas-Grid Coupling

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

Chertkov, Michael; Lebedev, Vladimir; Backhaus, Scott N.

2014-09-05

The revolution of hydraulic fracturing has dramatically increased the supply and lowered the cost of natural gas in the United States driving an expansion of natural gas-fired generation capacity in many electrical grids. Unrelated to the natural gas expansion, lower capital costs and renewable portfolio standards are driving an expansion of intermittent renewable generation capacity such as wind and photovoltaic generation. These two changes may potentially combine to create new threats to the reliability of these interdependent energy infrastructures. Natural gas-fired generators are often used to balance the fluctuating output of wind generation. However, the time-varying output of these generatorsmore » results in time-varying natural gas burn rates that impact the pressure in interstate transmission pipelines. Fluctuating pressure impacts the reliability of natural gas deliveries to those same generators and the safety of pipeline operations. We adopt a partial differential equation model of natural gas pipelines and use this model to explore the effect of intermittent wind generation on the fluctuations of pressure in natural gas pipelines. The mean square pressure fluctuations are found to grow linearly in time with points of maximum deviation occurring at the locations of flow reversals.« less

A multimodal instrument for real-time in situ study of ultrasound and cavitation mediated drug delivery.

PubMed

Bian, Shuning; Seth, Anjali; Daly, Dan; Carlisle, Robert; Stride, Eleanor

2017-03-01

The development of a multimodal instrument capable of real-time in situ measurements of cavitation activity and effect in tissue mimicking phantoms during ultrasound and cavitation mediated drug delivery experiments is described here. The instrument features an acoustic arm that can expose phantoms to high-intensity focused-ultrasound while measuring cavitation activity and an optical arm that monitors cavitation effect using confocal microscopy. This combination of modalities allows real-time in situ characterisation of drug delivery in tissue and tissue mimicking phantoms during ultrasound and cavitation mediated drug delivery experiments. A representative result, obtained with a tissue mimicking phantom and acoustically activated droplets, is presented here as a demonstration of the instrument's capabilities and potential applications.

On the use of volumetric-modulated arc therapy for single-fraction thoracic vertebral metastases stereotactic body radiosurgery

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

Pokhrel, Damodar, E-mail: damodar.pokhrel@uky.edu; Sood, Sumit; McClinton, Christopher

To retrospectively evaluate quality, efficiency, and delivery accuracy of volumetric-modulated arc therapy (VMAT) plans for single-fraction treatment of thoracic vertebral metastases using image-guided stereotactic body radiosurgery (SBRS) after RTOG 0631 dosimetric compliance criteria. After obtaining credentialing for MD Anderson spine phantom irradiation validation, 10 previously treated patients with thoracic vertebral metastases with noncoplanar hybrid arcs using 1 to 2 3D-conformal partial arcs plus 7 to 9 intensity-modulated radiation therapy beams were retrospectively re-optimized with VMAT using 3 full coplanar arcs. Tumors were located between T2 and T12. Contrast-enhanced T1/T2-weighted magnetic resonance images were coregistered with planning computed tomography and planningmore » target volumes (PTV) were between 14.4 and 230.1 cc (median = 38.0 cc). Prescription dose was 16 Gy in 1 fraction with 6 MV beams at Novalis-TX linear accelerator consisting of micro multileaf collimators. Each plan was assessed for target coverage using conformality index, the conformation number, the ratio of the volume receiving 50% of the prescription dose over PTV, R50%, homogeneity index (HI), and PTV-1600 coverage per RTOG 0631 requirements. Organs-at-risk doses were evaluated for maximum doses to spinal cord (D{sub 0.03} {sub cc}, D{sub 0.35} {sub cc}), partial spinal cord (D{sub 10%}), esophagus (D{sub 0.03} {sub cc} and D{sub 5} {sub cc}), heart (D{sub 0.03} {sub cc} and D{sub 15} {sub cc}), and lung (V{sub 5}, V{sub 10}, and maximum dose to 1000 cc of lung). Dose delivery efficiency and accuracy of each VMAT-SBRS plan were assessed using quality assurance (QA) plan on MapCHECK device. Total beam-on time was recorded during QA procedure, and a clinical gamma index (2%/2 mm and 3%/3 mm) was used to compare agreement between planned and measured doses. All 10 VMAT-SBRS plans met RTOG 0631 dosimetric requirements for PTV coverage. The plans demonstrated highly conformal and homogenous coverage of the vertebral PTV with mean HI, conformality index, conformation number, and R{sub 50%} values of 0.13 ± 0.03 (range: 0.09 to 0.18), 1.03 ± 0.04 (range: 0.98 to 1.09), 0.81 ± 0.06 (range: 0.72 to 0.89), and 4.2 ± 0.94 (range: 2.7 to 5.4), respectively. All 10 patients met protocol guidelines with maximum dose to spinal cord (average: 8.83 ± 1.9 Gy, range: 5.9 to 10.9 Gy); dose to 0.35 cc of spinal cord (average: 7.62 ± 1.7 Gy, range: 5.4 to 9.6 Gy); and dose to 10% of partial spinal cord (average 6.31 ± 1.5 Gy, range: 3.5 to 8.5 Gy) less than 14, 10, and 10 Gy, respectively. For all 10 patients, the maximum dose to esophagus (average: 9.41 ± 4.3 Gy, range: 1.5 to 14.9 Gy) and dose to 5 cc of esophagus (average: 7.43 ± 3.8 Gy, range: 1.1 to 11.8 Gy) were kept less than protocol requirements 16 Gy and 11.9 Gy, respectively. In a similar manner, all 10 patients met protocol compliance criteria with maximum dose to heart (average: 4.62 ± 3.5 Gy, range: 1.3 to 10.2 Gy) and dose to 15 cc of heart (average: 2.23 ± 1.8 Gy, range: 0.3 to 5.6 Gy) less than 22 and 16 Gy, respectively. The dose to the lung was retained much lower than protocol guidelines for all 10 patients. The total number of monitor units was, on average, 6919 ± 1187. The average beam-on time was 11.5 ± 2.0 minutes. The VMAT plans demonstrated dose delivery accuracy of 95.8 ± 0.7%, on average, for clinical gamma passing rate with 2%/2 mm criteria and 98.3 ± 0.8%, on average, with 3%/3 mm criteria. All VMAT-SBRS plans were considered clinically acceptable per RTOG 0631 dosimetric compliance criteria. VMAT planning provided highly conformal and homogenous dose distributions for the lower-dose vertebral PTV and the spinal cord as well as organs-at-risk such as esophagus, heart, and lung. Higher QA pass rates and shorter beam-on time suggest that VMAT-SBRS is a clinically feasible, fast, and effective treatment option for patients with thoracic vertebral metastases.« less

Hydrological control of large hurricane-induced lahars: evidence from rainfall-runoff modeling, seismic and video monitoring

NASA Astrophysics Data System (ADS)

Capra, Lucia; Coviello, Velio; Borselli, Lorenzo; Márquez-Ramírez, Víctor-Hugo; Arámbula-Mendoza, Raul

2018-03-01

The Volcán de Colima, one of the most active volcanoes in Mexico, is commonly affected by tropical rains related to hurricanes that form over the Pacific Ocean. In 2011, 2013 and 2015 hurricanes Jova, Manuel and Patricia, respectively, triggered tropical storms that deposited up to 400 mm of rain in 36 h, with maximum intensities of 50 mm h -1. The effects were devastating, with the formation of multiple lahars along La Lumbre and Montegrande ravines, which are the most active channels in sediment delivery on the south-southwest flank of the volcano. Deep erosion along the river channels and several marginal landslides were observed, and the arrival of block-rich flow fronts resulted in damages to bridges and paved roads in the distal reaches of the ravines. The temporal sequence of these flow events is reconstructed and analyzed using monitoring data (including video images, seismic records and rainfall data) with respect to the rainfall characteristics and the hydrologic response of the watersheds based on rainfall-runoff numerical simulation. For the studied events, lahars occurred 5-6 h after the onset of rainfall, lasted several hours and were characterized by several pulses with block-rich fronts and a maximum flow discharge of 900 m3 s -1. Rainfall-runoff simulations were performer using the SCS-curve number and the Green-Ampt infiltration models, providing a similar result in the detection of simulated maximum watershed peaks discharge. Results show different behavior for the arrival times of the first lahar pulses that correlate with the simulated catchment's peak discharge for La Lumbre ravine and with the peaks in rainfall intensity for Montegrande ravine. This different behavior is related to the area and shape of the two watersheds. Nevertheless, in all analyzed cases, the largest lahar pulse always corresponds with the last one and correlates with the simulated maximum peak discharge of these catchments. Data presented here show that flow pulses within a lahar are not randomly distributed in time, and they can be correlated with rainfall peak intensity and/or watershed discharge, depending on the watershed area and shape. This outcome has important implications for hazard assessment during extreme hydro-meteorological events, as it could help in providing real-time alerts. A theoretical rainfall distribution curve was designed for Volcán de Colima based on the rainfall and time distribution of hurricanes Manuel and Patricia. This can be used to run simulations using weather forecasts prior to the actual event, in order to estimate the arrival time of main lahar pulses, usually characterized by block-rich fronts, which are responsible for most of the damage to infrastructure and loss of goods and lives.

Increase in Cesarean Operative Time Following Institution of the 80-Hour Workweek

PubMed Central

Smrtka, Michael P.; Gunatilake, Ravindu P.; Harris, Benjamin; Yu, Miao; Lan, Lan; Brancazio, Leo R.; Valea, Fidel A.; Grotegut, Chad A.; Brown, Haywood L.

2015-01-01

Background  In 2003, the Accreditation Council for Graduate Medical Education limited resident duty hours to 80 hours per week. More than a decade later, the effect of the limits on resident clinical competence is not fully understood. Objective  We sought to assess the effect of duty hour restrictions on resident performance of an uncomplicated cesarean delivery. Methods  We reviewed unlabored primary cesarean deliveries at Duke University Hospital after 34 weeks gestation, between 2003 and 2011. Descriptive statistics and linear regression were used to compare total operative time with incision to delivery time as a function of years since institution of the 80-hour workweek. Resident training level, subject body mass index, estimated blood loss, and skin closure method were controlled for in the regression model. Results  We identified 444 deliveries that met study criteria. The mean (SD) total operative time in 2003–2004 was 43.3 (14.3) minutes and 59.6 (10.7) minutes in 2010–2011 (P < .001). Multivariable regression demonstrated an increase in total operative time of 1.9 min/y (P < .001) but no change in incision to delivery time (P = .05). The magnitude of increased operative time was seen among junior residents (2.0 min/y, P < .001) compared to that of senior residents (1.2 min/y, P = .06). Conclusions  Since introduction of the 2003 duty hour limits, there has been an increase of nearly 20 minutes in the time required for a routine cesarean delivery. It is unclear if the findings are due to a change in residency duty hours or to another aspect of residency training. PMID:26457141

An Overview On Various Approaches And Recent Patents On Gastroretentive Drug Delivery Systems.

PubMed

Kumar, Manoj; Kaushik, Deepak

2018-03-08

Drugs having absorption window in the stomach or upper small intestine has restricted bioavailability with conventional dosage forms. The gastric residence time of these dosage forms is usually short and they do not show drug release for prolonged period of time. To avoid these problems and to enhance the bioavailability and gastric retention time of these drugs, controlled drug delivery systems with prolonged gastric retention time are currently being developed. This review highlights the various pharmaceutical approaches for gastroretention such as floating drug delivery systems, mucoadhesive systems, high density systems, expandable and swelling systems, superporous hydrogels systems, magnetic systems, ion exchange resin system and recent patents filed or granted for these approaches. Recently some patents are also reported where a combination of various approaches are being employed to achieve very effective gastroretention. The various patent search sites were used to collect and analyze the information on gastroretentive drug delivery systems. The present study provides valuable information, advantages, limitations and future outlook of various gastroretentive drug delivery systems. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Grand-grand multiparity (more than 10 deliveries) does not convey a risk for osteoporosis.

PubMed

Turan, Volkan

2011-12-01

To examine whether multiparity is a risk factor for osteoporosis. Design. A retrospective evaluation. 16 grand-grand multiparous women and women who gave birth a maximum of three times (n= 15), aged 55-60 years. X-ray absorptiometry was used to examine lumbar spine (L(1) -L(4) ) and femoral bone mineral densities. The relation between parity and osteoporosis was investigated by separating the bone mineral density into three categories according to the score from the absorptiometry. The women had a similar body mass index and post-menopausal status, lumbar spine (L(1) -L(4) ) and femoral bone mineral densities. There was no relation between multiparity and osteoporosis development in the lumbar spine (r=-0.02; p=0.992) or total femoral (r=0.20; p=0.916) regions. Many pregnancies and childbirths along with long total lactation times do not appear to play a role in increasing the risk of osteoporosis at a more advanced age. © 2011 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2011 Nordic Federation of Societies of Obstetrics and Gynecology.

Pharmacokinetics of orally administered DL-α-lipoic acid in dogs.

PubMed

Zicker, Steven C; Avila, Albert; Joshi, Dinesh K; Gross, Kathy L

2010-11-01

To determine the pharmacokinetics of DL-α-lipoic acid in dogs when administered at 3 dosages via 3 methods of delivery. 27 clinically normal Beagles. In a 3 × 3 factorial Latin square design, 3 dosages (2.5, 12.5, and 25 mg/kg) of DL-α-lipoic acid were administered orally in a capsule form and provided without a meal, in a capsule form and provided with a meal, and as an ingredient included in an extruded dog food. Food was withheld for 12 hours prior to DL-α-lipoic acid administration. Blood samples were collected before (0 minutes) and at 15, 30, 45, 60, and 120 minutes after administration. Plasma concentrations of DL-α-lipoic acid were determined via high-performance liquid chromatography. A generalized linear models procedure was used to evaluate the effects of method of delivery and dosage. Noncompartmental analysis was used to determine pharmacokinetic parameters of DL-α-lipoic acid. Nonparametric tests were used to detect significant differences between pharmacokinetic parameters among treatment groups. A significant effect of dosage was observed regardless of delivery method. Method of delivery also significantly affected plasma concentrations of DL-α-lipoic acid, with extruded foods resulting in lowest concentration for each dosage administered. Maximum plasma concentration was significantly affected by method of delivery at each dosage administered. Other significant changes in pharmacokinetic parameters were variable and dependent on dosage and method of delivery. Values for pharmacokinetic parameters of orally administered DL-α-lipoic acid may differ significantly when there are changes in dosage, method of administration, and fed status.

Delivery performance of conventional aircraft by terminal-area, time-based air traffic control: A real-time simulation evaluation

NASA Technical Reports Server (NTRS)

Credeur, Leonard; Houck, Jacob A.; Capron, William R.; Lohr, Gary W.

1990-01-01

A description and results are presented of a study to measure the performance and reaction of airline flight crews, in a full workload DC-9 cockpit, flying in a real-time simulation of an air traffic control (ATC) concept called Traffic Intelligence for the Management of Efficient Runway-scheduling (TIMER). Experimental objectives were to verify earlier fast-time TIMER time-delivery precision results and obtain data for the validation or refinement of existing computer models of pilot/airborne performance. Experimental data indicated a runway threshold, interarrival-time-error standard deviation in the range of 10.4 to 14.1 seconds. Other real-time system performance parameters measured include approach speeds, response time to controller turn instructions, bank angles employed, and ATC controller message delivery-time errors.

SU-E-T-613: Dosimetric Consequences of Systematic MLC Leaf Positioning Errors

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

Kathuria, K; Siebers, J

2014-06-01

Purpose: The purpose of this study is to determine the dosimetric consequences of systematic MLC leaf positioning errors for clinical IMRT patient plans so as to establish detection tolerances for quality assurance programs. Materials and Methods: Dosimetric consequences were simulated by extracting mlc delivery instructions from the TPS, altering the file by the specified error, reloading the delivery instructions into the TPS, recomputing dose, and extracting dose-volume metrics for one head-andneck and one prostate patient. Machine error was simulated by offsetting MLC leaves in Pinnacle in a systematic way. Three different algorithms were followed for these systematic offsets, and aremore » as follows: a systematic sequential one-leaf offset (one leaf offset in one segment per beam), a systematic uniform one-leaf offset (same one leaf offset per segment per beam) and a systematic offset of a given number of leaves picked uniformly at random from a given number of segments (5 out of 10 total). Dose to the PTV and normal tissue was simulated. Results: A systematic 5 mm offset of 1 leaf for all delivery segments of all beams resulted in a maximum PTV D98 deviation of 1%. Results showed very low dose error in all reasonably possible machine configurations, rare or otherwise, which could be simulated. Very low error in dose to PTV and OARs was shown in all possible cases of one leaf per beam per segment being offset (<1%), or that of only one leaf per beam being offset (<.2%). The errors resulting from a high number of adjacent leaves (maximum of 5 out of 60 total leaf-pairs) being simultaneously offset in many (5) of the control points (total 10–18 in all beams) per beam, in both the PTV and the OARs analyzed, were similarly low (<2–3%). Conclusions: The above results show that patient shifts and anatomical changes are the main source of errors in dose delivered, not machine delivery. These two sources of error are “visually complementary” and uncorrelated (albeit not additive in the final error) and one can easily incorporate error resulting from machine delivery in an error model based purely on tumor motion.« less

49 CFR 386.6 - Service.

Code of Federal Regulations, 2010 CFR

2010-10-01

... valid as of the date and the time the document was mailed, or the date personal delivery of the document was refused. Service by delivery after 5 p.m. in the time zone in which the recipient will receive...

Integrated model for pricing, delivery time setting, and scheduling in make-to-order environments

NASA Astrophysics Data System (ADS)

Garmdare, Hamid Sattari; Lotfi, M. M.; Honarvar, Mahboobeh

2018-03-01

Usually, in make-to-order environments which work only in response to the customer's orders, manufacturers for maximizing the profits should offer the best price and delivery time for an order considering the existing capacity and the customer's sensitivity to both the factors. In this paper, an integrated approach for pricing, delivery time setting and scheduling of new arrival orders are proposed based on the existing capacity and accepted orders in system. In the problem, the acquired market demands dependent on the price and delivery time of both the manufacturer and its competitors. A mixed-integer non-linear programming model is presented for the problem. After converting to a pure non-linear model, it is validated through a case study. The efficiency of proposed model is confirmed by comparing it to both the literature and the current practice. Finally, sensitivity analysis for the key parameters is carried out.

Formulation, optimization, and evaluation of self-emulsifying drug delivery systems of nevirapine

PubMed Central

Chintalapudi, Ramprasad; Murthy, T. E. G. K.; Lakshmi, K. Rajya; Manohar, G. Ganesh

2015-01-01

Background: The aim of the present study was to formulate and optimize the self-emulsifying drug delivery systems (SEDDS) of nevirapine (NVP) by use of 22 factorial designs to enhance the oral absorption of NVP by improving its solubility, dissolution rate, and diffusion profile. SEDDS are the isotropic mixtures of oil, surfactant, co-surfactant and drug that form oil in water microemulsion when introduced into the aqueous phase under gentle agitation. Materials and Methods: Solubility of NVP in different oils, surfactants, and co-surfactants was determined for the screening of excipients. Pseudo-ternary phase diagrams were constructed by the aqueous titration method, and formulations were developed based on the optimum excipient combinations with the help of data obtained through the maximum micro emulsion region containing combinations of oil, surfactant, and co-surfactant. The formulations of SEDDS were optimized by 22 factorial designs. Results: The optimum formulation of SEDDS contains 32.5% oleic acid, 44.16% tween 20, and 11.9% polyethylene glycol 600 as oil, surfactant, and co-surfactant respectively. The SEDDS was evaluated for the following drug content, self-emulsification time, rheological properties, zeta potential, in vitro diffusion studies, thermodynamic stability studies, and in vitro dissolution studies. An increase in dissolution was achieved by SEDDS compared to pure form of NVP. Conclusion: Overall, this study suggests that the dissolution and oral bioavailability of NVP could be improved by SEDDS technology. PMID:26682191

Nicotine Delivery and Vaping Behavior During ad Libitum E-cigarette Access

PubMed Central

St.Helen, Gideon; Ross, Kathryn C.; Dempsey, Delia A.; Havel, Christopher M.; Jacob, Peyton; Benowitz, Neal L.

2017-01-01

Objective To characterize vaping behavior and nicotine intake during ad libitum e-cigarette access. Methods Thirteen adult e-cigarette users had 90 minutes of videotaped ad libitum access to their usual e-cigarette. Plasma nicotine was measured before and every 15 minutes after the first puff; subjective effects were measured before and after the session. Results Average puff duration and interpuff interval were 3.5±1.4 seconds (±SD) and 118±141 seconds, respectively. 12% of puffs were unclustered puffs while 43%, 28%, and 17% were clustered in groups of 2–5, 6–10, and >10 puffs, respectively. On average, 4.0±3.3 mg of nicotine was inhaled; the maximum plasma nicotine concentration (Cmax) was 12.8±8.5 ng/mL. Among the 8 tank users, number of puffs was positively correlated with amount of nicotine inhaled, Cmax, and area under the plasma nicotine concentration-time curve (AUC0→90min) while interpuff interval was negatively correlated with Cmax and AUC0→90. Conclusion Vaping patterns differ from cigarette smoking. Plasma nicotine levels were consistent with intermittent dosing of nicotine from e-cigarettes compared to the more bolus dosing from cigarettes. Differences in delivery patterns and peak levels of nicotine achieved could influence the addictiveness of e-cigarettes compared to conventional cigarettes. PMID:28393086

Diacerein niosomal gel for topical delivery: development, in vitro and in vivo assessment.

PubMed

El-Say, Khalid M; Abd-Allah, Fathy I; Lila, Ahmed E; Hassan, Abd El-Saboor A; Kassem, Alaa Eldin A

2016-01-01

The purpose of this study was to load diacerein (DCR) in niosomes by applying response surface methodology and incorporate these niosomes in gel base for topical delivery. Box-Behnken design was used to investigate the effect of charge-inducing agent (X1), surfactant HLB (X2) and sonication time (X3) on the vesicle size (Y1), entrapment efficiency (Y2) and cumulative drug released (Y3). DCR niosomal formulations were prepared by thin film hydration method. The optimized formula was incorporated in different gel bases. DCR niosomal gels were evaluated for homogeneity, rheological behavior; in vitro release and pharmacodynamic activity by carrageenan-induced hind paw edema method in the rat compared with DCR commercial gel. The results revealed that the mean vesicle sizes of the prepared niosomes ranged from 7.33 to 23.72 µm and the entrapment efficiency ranged from 9.52% to 58.43% with controlled release pattern over 8 h. DCR niosomal gels exhibited pseudoplastic flow with thixotropic behavior. The pharmacodynamic activity of DCR niosomal gel in 3% HPMC showed significant, 37.66%, maximum inhibition of edema size in comparison with 20.83% for the commercial gel (p < 0.05). These results recommended the incorporation of DCR niosomes in 3% HPMC for topical application as a potent anti-inflammatory drug for the treatment of osteoarthritis.

Physiologically Based Pharmacokinetic and Absorption Modeling for Osmotic Pump Products.

PubMed

Ni, Zhanglin; Talattof, Arjang; Fan, Jianghong; Tsakalozou, Eleftheria; Sharan, Satish; Sun, Dajun; Wen, Hong; Zhao, Liang; Zhang, Xinyuan

2017-07-01

Physiologically based pharmacokinetic (PBPK) and absorption modeling approaches were employed for oral extended-release (ER) drug products based on an osmotic drug delivery system (osmotic pumps). The purpose was to systemically evaluate the in vivo relevance of in vitro dissolution for this type of formulation. As expected, in vitro dissolution appeared to be generally predictive of in vivo PK profiles, because of the unique feature of this delivery system that the in vitro and in vivo release of osmotic pump drug products is less susceptible to surrounding environment in the gastrointestinal (GI) tract such as pH, hydrodynamic, and food effects. The present study considered BCS (Biopharmaceutics Classification System) class 1, 2, and 3 drug products with half-lives ranging from 2 to greater than 24 h. In some cases, the colonic absorption models needed to be adjusted to account for absorption in the colon. C max (maximum plasma concentration) and AUCt (area under the concentration curve) of the studied drug products were sensitive to changes in colon permeability and segmental GI transit times in a drug product-dependent manner. While improvement of the methodology is still warranted for more precise prediction (e.g., colonic absorption and dynamic movement in the GI tract), the results from the present study further emphasized the advantage of using PBPK modeling in addressing product-specific questions arising from regulatory review and drug development.

The spatial distribution of behavior under varying frequencies of temporally scheduled water delivery.

PubMed Central

Ribes-Iñesta, E; Torres, C

2000-01-01

Two studies evaluated the effects of response-independent water deliveries on the location (on the floor of the experimental chamber) and position (height) of rats' behavior. In both experiments, fixed-time schedules delivered water in two dispensers that were located at opposite ends of the chamber. In Experiment 1, the two schedules provided complementary frequencies of water deliveries while the overall number of deliveries stayed constant. In Experiment 2, one of the schedules delivered water twice as frequently as the other; this proportion was kept constant while the overall density of water deliveries changed systematically. In both experiments, a single position (height) of behavior was dominant. Also, the percentage of time allocated to each dispenser was roughly proportional to the percentage of water deliveries associated with the dispensers. These data and additional considerations support the importance of examining the spatial properties and patterning of behavior. PMID:10784009

Anal incontinence among first time mothers - what happens in pregnancy and the first year after delivery?

PubMed

Johannessen, Hege Hølmo; Wibe, Arne; Stordahl, Arvid; Sandvik, Leiv; Mørkved, Siv

2015-09-01

Pregnancy- and delivery-related factors affect postpartum anal incontinence. We aimed to explore changes in continence status among primiparas from late pregnancy through the first year postpartum. In this prospective cohort study set in two Norwegian hospitals, 862 healthy primiparas completed questionnaires about the main outcome measure anal incontinence, including flatus incontinence and urgency, at three time points; late pregnancy, 6 and 12 months postpartum. Socioeconomic and delivery-related data were obtained from hospital records. Logistic regression analyses were applied to determine the association between continence status at 12 months postpartum, and continence status in late pregnancy, 6 months postpartum, demographic and delivery-related characteristics. Among the 189 (22%) primiparas reporting anal incontinence in late pregnancy, 34 (18%) had persistent anal incontinence 1 year later. Forty-eight (43%) of the 113 women incontinent at 6 months postpartum experienced persistent anal incontinence at 12 months. Eight percent of previously continent women reported new onset anal incontinence at 6 and 12 months after delivery. Occipitoposterior presentation was the only delivery-related factor increasing the risk of postpartum anal incontinence [odds ratio (OR) 1.8, 95% confidence interval (CI) 1.0-3.4]. Young age increased the risk of anal incontinence at 1 year after delivery, whereas incontinence in late pregnancy increased the risk of anal incontinence persisting through 6 and 12 months postpartum. In most first-time mothers with postpartum anal incontinence, the onset of anal incontinence was before delivery. Except for occipitoposterior presentation, no delivery-related factors increased the risk of postpartum anal incontinence. This may indicate that hormonal, mechanical or neuromuscular changes in pregnancy affect long-term anal incontinence more than vaginal delivery. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

Reinforcement: Food Signals the Time and Location of Future Food

PubMed Central

Cowie, Sarah; Davison, Michael; Elliffe, Douglas

2011-01-01

It has long been understood that food deliveries may act as signals of future food location, and not only as strengtheners of prefood responding as the law of effect suggests. Recent research has taken this idea further—the main effect of food deliveries, or other “reinforcers”, may be signaling rather than strengthening. The present experiment investigated the ability of food deliveries to signal food contingencies across time after food. In Phase 1, the next food delivery was always equally likely to be arranged for a left- or a right-key response. Conditions were arranged such that the next food delivery was likely to occur either sooner on the left (or right) key, or sooner on the just-productive (or not-just-productive) key. In Phase 2, similar contingencies were arranged, but the last-food location was signaled by a red keylight. Preference, measured in 2-s bins across interfood intervals, was jointly controlled by the likely time and location of the next food delivery. In Phase 1, when any food delivery signaled a likely sooner next food delivery on a particular key, postfood preference was strongly toward that key, and moved toward the other key across the interreinforcer interval. In other conditions in which food delivery on the two keys signaled different subsequent contingencies, postfood preference was less extreme, and quickly moved toward indifference. In Phase 2, in all three conditions, initial preference was strongly toward the likely-sooner food key, and moved to the other key across the interfood interval. In both phases, at a more extended level of analysis, sequences of same-key food deliveries caused a small increase in preference for the just-productive key, suggesting the presence of a “reinforcement effect”, albeit one that was very small. PMID:21765546

Comparison of the Pharmacokinetics of Nicotine Following Single and Ad Libitum Use of a Tobacco Heating System or Combustible Cigarettes

PubMed Central

Picavet, Patrick; Haziza, Christelle; Lama, Nicola; Weitkunat, Rolf

2016-01-01

Introduction: We aimed to compare the pharmacokinetics of nicotine between the heat-not-burn Tobacco Heating System 2.1 (THS 2.1) and combustible cigarettes (CCs). We also examined whether the subjective urge to smoke was associated with the pharmacokinetics of nicotine. Methods: This open-label, randomized, two-period, two-sequence crossover study conducted in 28 healthy smokers assessed the pharmacokinetics of nicotine after single and ad libitum use of the THS 2.1 or CCs. During the 7-day confinement period, blood samples were drawn for pharmacokinetic analysis. Subjective effects related to THS 2.1 or CC use were assessed using the Questionnaire of Smoking Urges (QSU-Brief). Results: The nicotine delivery rate was similar with the THS 2.1 and CCs after single and ad libitum use. The time to the maximum nicotine concentration was 8 minutes after single use of the THS 2.1 and CCs. The time to the peak concentration following ad libitum use was similar between the THS 2.1 and CCs. The maximum plasma nicotine concentration after single use of the THS 2.1 was 8.4ng/mL, 70.3% of that obtained with CCs. A transient reduction from baseline in the urge to smoke of 40% was observed 15 minutes after the single use of both the THS 2.1 and CCs. The mean QSU-Brief total scores following single and ad libitum use were similar for the THS 2.1 and CCs. Conclusions: These results suggest that the THS 2.1 effectively delivers nicotine and achieves similar pharmacokinetic profiles to CCs. The THS 2.1 also reduced the urge to smoke similarly to CCs. Implications: Reducing exposure to toxicants and safer delivery of nicotine are among the strategies that may reduce the harm of smoking-related diseases. In the present study, we investigated the pharmacokinetics of nicotine and their effects on the urge to smoke using the THS 2.1. It was developed to replicate the ritual of smoking as closely as possible by providing nicotine in a way that mimics CC smoking, but limits pyrolysis and combustion by heating tobacco at a much lower temperature than CCs (heat-not-burn). PMID:26438645

Comparison of the Pharmacokinetics of Nicotine Following Single and Ad Libitum Use of a Tobacco Heating System or Combustible Cigarettes.

PubMed

Picavet, Patrick; Haziza, Christelle; Lama, Nicola; Weitkunat, Rolf; Lüdicke, Frank

2016-05-01

We aimed to compare the pharmacokinetics of nicotine between the heat-not-burn Tobacco Heating System 2.1 (THS 2.1) and combustible cigarettes (CCs). We also examined whether the subjective urge to smoke was associated with the pharmacokinetics of nicotine. This open-label, randomized, two-period, two-sequence crossover study conducted in 28 healthy smokers assessed the pharmacokinetics of nicotine after single and ad libitum use of the THS 2.1 or CCs. During the 7-day confinement period, blood samples were drawn for pharmacokinetic analysis. Subjective effects related to THS 2.1 or CC use were assessed using the Questionnaire of Smoking Urges (QSU-Brief). The nicotine delivery rate was similar with the THS 2.1 and CCs after single and ad libitum use. The time to the maximum nicotine concentration was 8 minutes after single use of the THS 2.1 and CCs. The time to the peak concentration following ad libitum use was similar between the THS 2.1 and CCs. The maximum plasma nicotine concentration after single use of the THS 2.1 was 8.4 ng/mL, 70.3% of that obtained with CCs. A transient reduction from baseline in the urge to smoke of 40% was observed 15 minutes after the single use of both the THS 2.1 and CCs. The mean QSU-Brief total scores following single and ad libitum use were similar for the THS 2.1 and CCs. These results suggest that the THS 2.1 effectively delivers nicotine and achieves similar pharmacokinetic profiles to CCs. The THS 2.1 also reduced the urge to smoke similarly to CCs. Reducing exposure to toxicants and safer delivery of nicotine are among the strategies that may reduce the harm of smoking-related diseases. In the present study, we investigated the pharmacokinetics of nicotine and their effects on the urge to smoke using the THS 2.1. It was developed to replicate the ritual of smoking as closely as possible by providing nicotine in a way that mimics CC smoking, but limits pyrolysis and combustion by heating tobacco at a much lower temperature than CCs (heat-not-burn). © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.

Reporter nanoparticle that monitors its anticancer efficacy in real time

PubMed Central

Kulkarni, Ashish; Rao, Poornima; Natarajan, Siva; Goldman, Aaron; Sabbisetti, Venkata S.; Khater, Yashika; Korimerla, Navya; Chandrasekar, Vineethkrishna; Mashelkar, Raghunath A.; Sengupta, Shiladitya

2016-01-01

The ability to monitor the efficacy of an anticancer treatment in real time can have a critical effect on the outcome. Currently, clinical readouts of efficacy rely on indirect or anatomic measurements, which occur over prolonged time scales postchemotherapy or postimmunotherapy and may not be concordant with the actual effect. Here we describe the biology-inspired engineering of a simple 2-in-1 reporter nanoparticle that not only delivers a cytotoxic or an immunotherapy payload to the tumor but also reports back on the efficacy in real time. The reporter nanoparticles are engineered from a novel two-staged stimuli-responsive polymeric material with an optimal ratio of an enzyme-cleavable drug or immunotherapy (effector elements) and a drug function-activatable reporter element. The spatiotemporally constrained delivery of the effector and the reporter elements in a single nanoparticle produces maximum signal enhancement due to the availability of the reporter element in the same cell as the drug, thereby effectively capturing the temporal apoptosis process. Using chemotherapy-sensitive and chemotherapy-resistant tumors in vivo, we show that the reporter nanoparticles can provide a real-time noninvasive readout of tumor response to chemotherapy. The reporter nanoparticle can also monitor the efficacy of immune checkpoint inhibition in melanoma. The self-reporting capability, for the first time to our knowledge, captures an anticancer nanoparticle in action in vivo. PMID:27036008

Development of a probiotic delivery system from agrowastes, soy protein isolate, and microbial transglutaminase.

PubMed

Yew, Sok-Eng; Lim, Ting-Jin; Lew, Lee-Ching; Bhat, Rajeev; Mat-Easa, Azhar; Liong, Min-Tze

2011-04-01

Probiotic delivery system was developed via the use of microbial transglutaminase (MTG) cross-linked soy protein isolate (SPI) incorporated with agrowastes such as banana peel (BE), banana pulp (BU), and pomelo rind (PR). Inoculums of Lactobacillus bulgaricus FTDC 1511 were added to the cross-linked protein matrix. The incorporation of agrowastes had significantly (P<0.05) reduced the strength, pH value, and the lightness of the SPI gel carriers, while sodium dodecyl sulfate-polyacrylamide gel electrophoresis profiles revealed that the occurring cross-links within the SPI gel carriers were attributed to the addition of MTG. Scanning electron microscope micrographs illustrated that SPI carriers containing agrowastes have exhibited a less-dense protein matrix. All the SPI carriers possessed maximum swelling ratio at 4 to 4.5 within 15 min in simulated gastric fluid (SGF), whereas the maximum swelling ratios of SPI/BE, SPI/BU, and SPI/PR were higher compared to that of control in simulated intestinal fluid (SIF). Additionally, SPI carriers in SGF medium did not show degradation of structure, whereas a major collapse of network was observed in SIF medium, indicating controlled-release in the intestines. The addition of agrowastes into SPI carriers led to a significantly (P<0.0001) lower release of L. bulgaricus FTDC 1511 in SGF medium and a higher release in SIF medium, compared to that of the control. SPI carriers containing agrowastes may be useful transports for living probiotic cells through the stomach prior to delivery in the lower intestines.   Agrowastes could be utilized as a new probiotic carrier for enhanced gastrointestinal transit and during storage. This also reduces the amount of agrowastes accumulated.

Finasteride topical delivery systems for androgenetic alopecia.

PubMed

Khan, Muhammad Zia Ullah; Khan, Shujaat Ali; Ubaid, Muhammad; Shah, Aamna; Kousar, Rozina; Murtaza, Ghulam

2018-01-23

Androgenetic alopecia, generally recognized as male pattern baldness, is a gradually developing medical and physiological change, which is manifested by continuous hair-loss from scalp. Finasteride (4-aza-3-oxosteroid) is a potent anti-baldness compound that selectively and competitively inhibits the 5α-reductase isoenzymes. Prolonged oral use of finasteride leads to the emergence of sexual disorders including decrease in libido, gynecomastia, erectile dysfunction, ejaculation disorder, orgasm disorders and mood disturbances. Since, hair follicles widely home in 5α-reductase, topical formulations of finasteride in comparison to its oral formulations are expected to potentially reduce its systemic adverse effects. The analysis of literature has revealed some delivery systems developed for the enhanced and localized penetration of finasteride into the skin. These finasteride delivery systems include polymersomes, vesicular nanocarriers, vesicular ethosomal carriers, liposomes and niosomes, liquid crystalline nanoparticles, topical solutions and gels. The aim of this review article is to briefly amass all literature on topical delivery of finasteride to elaborate best dosage form, i.e. formulation having maximum permeation rate. This study will serve as a future perspective regarding topical delivery of finasteride. The literature analysis has exhibited that most of the previous investigators have used propylene glycol in their finasteride-loaded topical formulations, while poloxamer P407, monoolein, transcutol P and choline was used in few formulations. Moreover among all drug delivery systems, finasteride liposomal gel system consisting of 2% methyl cellulose and gel system containing poloxamer P407 exhibited the highest flux with a value of 28.4 ± 1.3 µg/cm2h and 23.1 ± 1.4 µg/cm2h, respectively. Several topical drug delivery techniques such as topical microneedles, aerosol foams, nanoemulsions, microsponges, and emulsifier free formulations, fullerenes, ointments, pastes, creams, gel and lotions are still to be worthy regarding finasteride topical delivery in future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A continuous arc delivery optimization algorithm for CyberKnife m6.

PubMed

Kearney, Vasant; Descovich, Martina; Sudhyadhom, Atchar; Cheung, Joey P; McGuinness, Christopher; Solberg, Timothy D

2018-06-01

This study aims to reduce the delivery time of CyberKnife m6 treatments by allowing for noncoplanar continuous arc delivery. To achieve this, a novel noncoplanar continuous arc delivery optimization algorithm was developed for the CyberKnife m6 treatment system (CyberArc-m6). CyberArc-m6 uses a five-step overarching strategy, in which an initial set of beam geometries is determined, the robotic delivery path is calculated, direct aperture optimization is conducted, intermediate MLC configurations are extracted, and the final beam weights are computed for the continuous arc radiation source model. This algorithm was implemented on five prostate and three brain patients, previously planned using a conventional step-and-shoot CyberKnife m6 delivery technique. The dosimetric quality of the CyberArc-m6 plans was assessed using locally confined mutual information (LCMI), conformity index (CI), heterogeneity index (HI), and a variety of common clinical dosimetric objectives. Using conservative optimization tuning parameters, CyberArc-m6 plans were able to achieve an average CI difference of 0.036 ± 0.025, an average HI difference of 0.046 ± 0.038, and an average LCMI of 0.920 ± 0.030 compared with the original CyberKnife m6 plans. Including a 5 s per minute image alignment time and a 5-min setup time, conservative CyberArc-m6 plans achieved an average treatment delivery speed up of 1.545x ± 0.305x compared with step-and-shoot plans. The CyberArc-m6 algorithm was able to achieve dosimetrically similar plans compared to their step-and-shoot CyberKnife m6 counterparts, while simultaneously reducing treatment delivery times. © 2018 American Association of Physicists in Medicine.

Comparison of self-administered survey questionnaire responses collected using mobile apps versus other methods.

PubMed

Marcano Belisario, José S; Jamsek, Jan; Huckvale, Kit; O'Donoghue, John; Morrison, Cecily P; Car, Josip

2015-07-27

Self-administered survey questionnaires are an important data collection tool in clinical practice, public health research and epidemiology. They are ideal for achieving a wide geographic coverage of the target population, dealing with sensitive topics and are less resource-intensive than other data collection methods. These survey questionnaires can be delivered electronically, which can maximise the scalability and speed of data collection while reducing cost. In recent years, the use of apps running on consumer smart devices (i.e., smartphones and tablets) for this purpose has received considerable attention. However, variation in the mode of delivering a survey questionnaire could affect the quality of the responses collected. To assess the impact that smartphone and tablet apps as a delivery mode have on the quality of survey questionnaire responses compared to any other alternative delivery mode: paper, laptop computer, tablet computer (manufactured before 2007), short message service (SMS) and plastic objects. We searched MEDLINE, EMBASE, PsycINFO, IEEEXplore, Web of Science, CABI: CAB Abstracts, Current Contents Connect, ACM Digital, ERIC, Sociological Abstracts, Health Management Information Consortium, the Campbell Library and CENTRAL. We also searched registers of current and ongoing clinical trials such as ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform. We also searched the grey literature in OpenGrey, Mobile Active and ProQuest Dissertation & Theses. Lastly, we searched Google Scholar and the reference lists of included studies and relevant systematic reviews. We performed all searches up to 12 and 13 April 2015. We included parallel randomised controlled trials (RCTs), crossover trials and paired repeated measures studies that compared the electronic delivery of self-administered survey questionnaires via a smartphone or tablet app with any other delivery mode. We included data obtained from participants completing health-related self-administered survey questionnaire, both validated and non-validated. We also included data offered by both healthy volunteers and by those with any clinical diagnosis. We included studies that reported any of the following outcomes: data equivalence; data accuracy; data completeness; response rates; differences in the time taken to complete a survey questionnaire; differences in respondent's adherence to the original sampling protocol; and acceptability to respondents of the delivery mode. We included studies that were published in 2007 or after, as devices that became available during this time are compatible with the mobile operating system (OS) framework that focuses on apps. Two review authors independently extracted data from the included studies using a standardised form created for this systematic review in REDCap. They then compared their forms to reach consensus. Through an initial systematic mapping on the included studies, we identified two settings in which survey completion took place: controlled and uncontrolled. These settings differed in terms of (i) the location where surveys were completed, (ii) the frequency and intensity of sampling protocols, and (iii) the level of control over potential confounders (e.g., type of technology, level of help offered to respondents). We conducted a narrative synthesis of the evidence because a meta-analysis was not appropriate due to high levels of clinical and methodological diversity. We reported our findings for each outcome according to the setting in which the studies were conducted. We included 14 studies (15 records) with a total of 2275 participants; although we included only 2272 participants in the final analyses as there were missing data for three participants from one included study.Regarding data equivalence, in both controlled and uncontrolled settings, the included studies found no significant differences in the mean overall scores between apps and other delivery modes, and that all correlation coefficients exceeded the recommended thresholds for data equivalence. Concerning the time taken to complete a survey questionnaire in a controlled setting, one study found that an app was faster than paper, whereas the other study did not find a significant difference between the two delivery modes. In an uncontrolled setting, one study found that an app was faster than SMS. Data completeness and adherence to sampling protocols were only reported in uncontrolled settings. Regarding the former, an app was found to result in more complete records than paper, and in significantly more data entries than an SMS-based survey questionnaire. Regarding adherence to the sampling protocol, apps may be better than paper but no different from SMS. We identified multiple definitions of acceptability to respondents, with inconclusive results: preference; ease of use; willingness to use a delivery mode; satisfaction; effectiveness of the system informativeness; perceived time taken to complete the survey questionnaire; perceived benefit of a delivery mode; perceived usefulness of a delivery mode; perceived ability to complete a survey questionnaire; maximum length of time that participants would be willing to use a delivery mode; and reactivity to the delivery mode and its successful integration into respondents' daily routine. Finally, regardless of the study setting, none of the included studies reported data accuracy or response rates. Our results, based on a narrative synthesis of the evidence, suggest that apps might not affect data equivalence as long as the intended clinical application of the survey questionnaire, its intended frequency of administration and the setting in which it was validated remain unchanged. There were no data on data accuracy or response rates, and findings on the time taken to complete a self-administered survey questionnaire were contradictory. Furthermore, although apps might improve data completeness, there is not enough evidence to assess their impact on adherence to sampling protocols. None of the included studies assessed how elements of user interaction design, survey questionnaire design and intervention design might influence mode effects. Those conducting research in public health and epidemiology should not assume that mode effects relevant to other delivery modes apply to apps running on consumer smart devices. Those conducting methodological research might wish to explore the issues highlighted by this systematic review.

Reducing Bottlenecks to Improve the Efficiency of the Lung Cancer Care Delivery Process: A Process Engineering Modeling Approach to Patient-Centered Care.

PubMed

Ju, Feng; Lee, Hyo Kyung; Yu, Xinhua; Faris, Nicholas R; Rugless, Fedoria; Jiang, Shan; Li, Jingshan; Osarogiagbon, Raymond U

2017-12-01

The process of lung cancer care from initial lesion detection to treatment is complex, involving multiple steps, each introducing the potential for substantial delays. Identifying the steps with the greatest delays enables a focused effort to improve the timeliness of care-delivery, without sacrificing quality. We retrospectively reviewed clinical events from initial detection, through histologic diagnosis, radiologic and invasive staging, and medical clearance, to surgery for all patients who had an attempted resection of a suspected lung cancer in a community healthcare system. We used a computer process modeling approach to evaluate delays in care delivery, in order to identify potential 'bottlenecks' in waiting time, the reduction of which could produce greater care efficiency. We also conducted 'what-if' analyses to predict the relative impact of simulated changes in the care delivery process to determine the most efficient pathways to surgery. The waiting time between radiologic lesion detection and diagnostic biopsy, and the waiting time from radiologic staging to surgery were the two most critical bottlenecks impeding efficient care delivery (more than 3 times larger compared to reducing other waiting times). Additionally, instituting surgical consultation prior to cardiac consultation for medical clearance and decreasing the waiting time between CT scans and diagnostic biopsies, were potentially the most impactful measures to reduce care delays before surgery. Rigorous computer simulation modeling, using clinical data, can provide useful information to identify areas for improving the efficiency of care delivery by process engineering, for patients who receive surgery for lung cancer.

Use of pharmacy delivery robots in intensive care units.

PubMed

Summerfield, Marc R; Seagull, F Jacob; Vaidya, Neelesh; Xiao, Yan

2011-01-01

The use of pharmacy delivery robots in an institution's intensive care units was evaluated. In 2003, the University of Maryland Medical Center (UMMC) began a pilot program to determine the logistic capability and functional utility of robotic technology in the delivery of medications from satellite pharmacies to patient care units. Three satellite pharmacies currently used the robotic system. Five data sources (electronic robot activation records, logs, interviews, surveys, and observations) were used to assess five key aspects of robotic delivery: robot use, reliability, timeliness, cost minimization, and acceptance. A 19-item survey using a 7-point Likert-type scale was developed to determine if pharmacy delivery robots changed nurses' perception of pharmacy service. The components measured included general satisfaction, reliability, timeliness, stat orders, services, interaction with pharmacy, and status tracking. A total of 23 pre-implementation, 96 post-implementation, and 30 two-year follow-up surveys were completed. After implementation of the robotic delivery system, time from fax to label, order preparation time, and idle time for medications to be delivered decreased, while nurses' general satisfaction with the pharmacy and opinion of the reliability of pharmacy delivery significantly increased. Robotic delivery did not influence the perceived quality of delivery service or the timeliness of orders or stat orders. Robot reliability was a major issue for the technician but not for pharmacists, who did not have as much interaction with the devices. By considering the needs of UMMC and its patients and matching them with available technology, the institution was able to improve the medication-use process and timeliness of medication departure from the pharmacy.

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.

Department of Defense Finance and Accounting Service FY 1996/1997 Biennial Budget Estimates, February 1995.

DTIC Science & Technology

1995-02-01

Descriptive Summary 2 FIP Resources and Indefinite Delivery - Quantity Contracts 3 Central Design Activity Summary 4 Accesion For NTIS CRA&IDTIC TAB...interface with financial systems should be integrated into the standard architecture of the Military Departments iii to ensure maximum cost...provided to support and maintain the DFAS enterprise local area network initiative to establish a standardized architecture for office automation and

Public Works Operations at U.S. Army Garrison-Yongsan, Korea

DTIC Science & Technology

2010-05-04

services to its customers in the most effective and efficient manner. We examined DPW contract actions of $5.9 million, purchases from the Prime...delivery orders to achieve maximum effectiveness and efficiency, which resulted in questionable costs of up to $924,000, including $79,851 in...internally consistent, contract actions are well documented, and inspections are complete and comprehensive; use the most cost- effective method for

A Novel Multilayered Multidisk Oral Tablet for Chronotherapeutic Drug Delivery

PubMed Central

Khan, Zaheeda; Choonara, Yahya E.; du Toit, Lisa C.; Ndesendo, Valence M. K.; Pillay, Viness

2013-01-01

A Multilayered Multidisk Tablet (MLMDT) comprising two drug-loaded disks enveloped by three drug-free barrier layers was developed for use in chronotherapeutic disorders, employing two model drugs, theophylline and diltiazem HCl. The MLMDT was designed to achieve two pulses of drug release separated by a lag phase. The polymer disk comprised hydroxyethylcellulose (HEC) and ethylcellulose (EC) granulated using an aqueous dispersion of EC. The polymeric barrier layers constituted a combination of pectin/Avicel (PBL) (1st barrier layer) and hydroxypropylmethylcellulose (HPMC) (HBL1 and HBL2) as the 2nd and 3rd barrier layers, respectively. Sodium bicarbonate was incorporated into the diltiazem-containing formulation for delayed drug release. Erosion and swelling studies confirmed the manner in which the drug was released with theophylline formulations exhibiting a maximum swelling of 97% and diltiazem containing formulations with a maximum swelling of 119%. FTIR spectra displayed no interactions between drugs and polymers. Molecular mechanics simulations were undertaken to predict the possible orientation of the polymer morphologies most likely affecting the MLMDT performance. The MLMDT provided two pulses of drug release, separated by a lag phase, and additionally it displayed desirable friability, hardness, and uniformity of mass indicating a stable formulation that may be a desirable candidate for chronotherapeutic drug delivery. PMID:24024200

Optimization of a Diaphragm for a Micro-Shock Tube-Based Drug Delivery Method

PubMed Central

Rathod, Vivek T.; Mahapatra, Debiprosad Roy

2017-01-01

This paper presents the design optimization of diaphragms for a micro-shock tube-based drug delivery device. The function of the diaphragm is to impart the required velocity and direction to the loosely held drug particles on the diaphragm through van der Waals interaction. The finite element model-based studies involved diaphragms made up of copper, brass and aluminium. The study of the influence of material and geometric parameters serves as a vital tool in optimizing the magnitude and direction of velocity distribution on the diaphragm surface. Experiments carried out using a micro-shock tube validate the final deformed shape of the diaphragms determined from the finite element simulation. The diaphragm yields a maximum velocity of 335 m/s for which the maximum deviation of the velocity vector is 0.62°. Drug particles that travel to the destination target tissue are simulated using the estimated velocity distribution and angular deviation. Further, a theoretical model of penetration helps in the prediction of the drug particle penetration in the skin tissue like a target, which is found to be 0.126 mm. The design and calibration procedure of a micro-shock tube device to alter drug particle penetration considering the skin thickness and property are presented. PMID:28952503

Better delivery/pick up routes in the presence of uncertainty.

DOT National Transportation Integrated Search

2007-08-01

We consider the Courier Delivery Problem, a variant of the Vehicle Routing Problem with : time windows in which customers appear probabilistically and their service times are uncertain. : We use scenario-based stochastic optimization with recourse fo...

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.

Dosimetric comparison of a 6-MV flattening-filter and a flattening-filter-free beam for lung stereotactic ablative radiotherapy treatment

NASA Astrophysics Data System (ADS)

Kim, Yon-Lae; Chung, Jin-Beom; Kim, Jae-Sung; Lee, Jeong-Woo; Kim, Jin-Young; Kang, Sang-Won; Suh, Tae-Suk

2015-11-01

The purpose of this study was to test the feasibility of clinical usage of a flattening-filter-free (FFF) beam for treatment with lung stereotactic ablative radiotherapy (SABR). Ten patients were treated with SABR and a 6-MV FFF beam for this study. All plans using volumetric modulated arc therapy (VMAT) were optimized in the Eclipse treatment planning system (TPS) by using the Acuros XB (AXB) dose calculation algorithm and were delivered by using a Varian TrueBeam ™ linear accelerator equipped with a high-definition (HD) multi-leaf collimator. The prescription dose used was 48 Gy in 4 fractions. In order to compare the plan using a conventional 6-MV flattening-filter (FF) beam, the SABR plan was recalculated under the condition of the same beam settings used in the plan employing the 6-MV FFF beam. All dose distributions were calculated by using Acuros XB (AXB, version 11) and a 2.5-mm isotropic dose grid. The cumulative dosevolume histograms (DVH) for the planning target volume (PTV) and all organs at risk (OARs) were analyzed. Technical parameters, such as total monitor units (MUs) and the delivery time, were also recorded and assessed. All plans for target volumes met the planning objectives for the PTV ( i.e., V95% > 95%) and the maximum dose ( i.e., Dmax < 110%) revealing adequate target coverage for the 6-MV FF and FFF beams. Differences in DVH for target volumes (PTV and clinical target volume (CTV)) and OARs on the lung SABR plans from the interchange of the treatment beams were small, but showed a marked reduction (52.97%) in the treatment delivery time. The SABR plan with a FFF beam required a larger number of MUs than the plan with the FF beam, and the mean difference in MUs was 4.65%. This study demonstrated that the use of the FFF beam for lung SABR plan provided better treatment efficiency relative to 6-MV FF beam. This strategy should be particularly beneficial for high dose conformity to the lung and decreased intra-fraction movements because of the shorter treatment delivery time. Future studies are necessary to assess the clinical outcome and the toxicity.

Design of a transdermal delivery system for aspirin as an antithrombotic drug.

PubMed

Ammar, H O; Ghorab, M; El-Nahhas, S A; Kamel, R

2006-12-11

Aspirin has become the gold standard to which newer antiplatelet drugs are compared for reducing risks of cardiovascular diseases, while keeping low cost. Oral aspirin has a repertoire of gastrointestinal side effects even at low doses and requires high frequent dosing because it undergoes extensive presystemic metabolism. Transdermal delivery offers an alternative route that bypasses the gut and may be more convenient and safer for aspirin delivery especially during long-term use. This study comprised formulation of aspirin in different topical bases. Release studies revealed that hydrocarbon gel allowed highest drug release. In vitro permeation studies revealed high drug permeation from hydrocarbon gel. Several chemical penetration enhancers were monitored for augmenting the permeation from this base. Combination of propylene glycol and alcohol showed maximum enhancing effect and, hence, was selected for biological investigation. The biological performance of the selected formulation was assessed by measuring the inhibition of platelet aggregation relevant to different dosage regimens aiming to minimize both drug dose and frequency of application. The results demonstrated the feasibility of successfully influencing platelet function and revealed that the drug therapeutic efficacy in transdermal delivery system is dose independent. Biological performance was re-assessed after storage and the results revealed stability and persistent therapeutic efficacy.

Technical Note: Direct measurement of continuous TMR data with a 1D tank and automated couch movements.

PubMed

Knutson, Nels C; Schmidt, Matthew C; Belley, Matthew D; Nguyen, Ngoc B; Li, H Harold; Sajo, Erno; Price, Michael J

2017-07-01

Real-time dynamic control of the linear accelerator, couch, and imaging parameters during radiation delivery was investigated as a novel technique for acquiring tissue maximum ratio (TMR) data. TrueBeam Developer Mode (Varian Medical Systems, Palo Alto, CA, USA) was used to control the linear accelerator using the Extensible Markup Language (XML). A single XML file was used to dynamically manipulate the machine, couch, and imaging parameters during radiation delivery. A TG-51 compliant 1D water tank was placed on the treatment couch, and used to position a detector at isocenter at a depth of 24.5 cm. A depth scan was performed towards the water surface. Via XML control, the treatment couch vertical position was simultaneously lowered at the same rate, maintaining the detector position at isocenter, allowing for the collection of TMR data. To ensure the detector remained at isocenter during the delivery, the in-room camera was used to monitor the detector. Continuous kV fluoroscopic images during 10 test runs further confirmed this result. TMR data at multiple Source to Detector Distances (SDD) and scan speeds were acquired to investigate their impact on the TMR data. Percentage depth dose (PDD) scans (for conversion to TMR) along with traditional discrete TMR data were acquired as a standard for comparison. More than 99.8% of the measured points had a gamma value (1%/1 mm) < 1 when compared with discrete or PDD converted TMR data. Fluoroscopic images showed that the concurrent couch and tank movements resulted in SDD errors < 1 mm. TMRs acquired at SDDs of 99, 100, and 101 cm showed differences less than 0.004. TrueBeam Developer Mode was used to collect continuous TMR data with the same accuracy as traditionally collected discrete data, but yielded higher sampled resolution and reduced acquisition time. This novel method does not require the modification of any equipment and does not use a 3D tank or reservoir. © 2017 American Association of Physicists in Medicine.

In vivo real-time monitoring system of electroporation mediated control of transdermal and topical drug delivery.

PubMed

Blagus, Tanja; Markelc, Bostjan; Cemazar, Maja; Kosjek, Tina; Preat, Veronique; Miklavcic, Damijan; Sersa, Gregor

2013-12-28

Electroporation (EP) is a physical method for the delivery of molecules into cells and tissues, including the skin. In this study, in order to control the degree of transdermal and topical drug delivery, EP at different amplitudes of electric pulses was evaluated. A new in vivo real-time monitoring system based on fluorescently labeled molecules was developed, for the quantification of transdermal and topical drug delivery. EP of the mouse skin was performed with new non-invasive multi-array electrodes, delivering different amplitudes of electric pulses ranging from 70 to 570 V, between the electrode pin pairs. Patches, soaked with 4 kDa fluorescein-isothiocyanate labeled dextran (FD), doxorubicin (DOX) or fentanyl (FEN), were applied to the skin before and after EP. The new monitoring system was developed based on the delivery of FD to and through the skin. FD relative quantity was determined with fluorescence microscopy imaging, in the treated region of the skin for topical delivery and in a segment of the mouse tail for transdermal delivery. The application of electric pulses for FD delivery resulted in enhanced transdermal delivery. Depending on the amplitude of electric pulses, it increased up to the amplitude of 360 V, and decreased at higher amplitudes (460 and 570 V). Topical delivery steadily enhanced with increasing the amplitude of the delivered electric pulses, being even higher than after tape stripping used as a positive control. The non-invasive monitoring of the delivery of DOX, a fluorescent chemotherapeutic drug, qualitatively and quantitatively confirmed the effects of EP at 360 and 570 V pulse amplitudes on topical and transdermal drug delivery. Delivery of FEN at 360 and 570 V pulse amplitudes verified the observed effects as obtained with FD and DOX, by the measured physiological responses of the mice as well as FEN plasma concentration. This study demonstrates that with the newly developed non-invasive multi-array electrodes and with the varying electric pulse amplitude, the amount of topical and transdermal drug delivery to the skin can be controlled. Furthermore, the newly developed monitoring system provides a tool for rapid real-time determination of both, transdermal and topical delivery, when the delivered molecule is fluorescent. © 2013 Elsevier B.V. All rights reserved.

Assessing delivery practices of mothers over time and over space in Uganda, 2003-2012.

PubMed

Sprague, Daniel A; Jeffery, Caroline; Crossland, Nadine; House, Thomas; Roberts, Gareth O; Vargas, William; Ouma, Joseph; Lwanga, Stephen K; Valadez, Joseph J

2016-01-01

It is well known that safe delivery in a health facility reduces the risks of maternal and infant mortality resulting from perinatal complications. What is less understood are the factors associated with safe delivery practices. We investigate factors influencing health facility delivery practices while adjusting for multiple other factors simultaneously, spatial heterogeneity, and trends over time. We fitted a logistic regression model to Lot Quality Assurance Sampling (LQAS) data from Uganda in a framework that considered individual-level covariates, geographical features, and variations over five time points. We accounted for all two-covariate interactions and all three-covariate interactions for which two of the covariates already had a significant interaction, were able to quantify uncertainty in outputs using computationally intensive cluster bootstrap methods, and displayed outputs using a geographical information system. Finally, we investigated what information could be predicted about districts at future time-points, before the next LQAS survey is carried out. To do this, we applied the model to project a confidence interval for the district level coverage of health facility delivery at future time points, by using the lower and upper end values of known demographics to construct a confidence range for the prediction and define priority groups. We show that ease of access, maternal age and education are strongly associated with delivery in a health facility; after accounting for this, there remains a significant trend towards greater uptake over time. We use this model together with known demographics to formulate a nascent early warning system that identifies candidate districts expected to have low prevalence of facility-based delivery in the immediate future. Our results support the hypothesis that increased development, particularly related to education and access to health facilities, will act to increase facility-based deliveries, a factor associated with reducing perinatal associated mortality. We provide a statistical method for using inexpensive and routinely collected monitoring and evaluation data to answer complex epidemiology and public health questions in a resource-poor setting. We produced a model based on this data that explained the spatial distribution of facility-based delivery in Uganda. Finally, we used this model to make a prediction about the future priority of districts that was validated by monitoring and evaluation data collected in the next year.

Challenging the 4- to 5-minute rule: from perimortem cesarean to resuscitative hysterotomy.

PubMed

Rose, Carl H; Faksh, Arij; Traynor, Kyle D; Cabrera, Daniel; Arendt, Katherine W; Brost, Brian C

2015-11-01

Although perimortem delivery has been recorded in the medical literature for millennia, the procedural intent has evolved to the current fetocentric approach, predicating timing of delivery following maternal cardiopulmonary arrest to optimize neonatal outcome. We suggest a call to action to reinforce the concept that if the uterus is palpable at or above the umbilicus, preparations for delivery should be made simultaneous with initiation of maternal resuscitative efforts; if maternal condition is not rapidly reversible, hysterotomy with delivery should be performed regardless of fetal viability or elapsed time since arrest. Cognizant of the difficulty in determining precise timing of arrest in clinical practice, if fetal status is already compromised further delay while attempting to assess fetal heart rate, locating optimal surgical equipment, or transporting to an operating room will result in unnecessary worsening of both maternal and fetal condition. Even if intrauterine demise has already occurred, maternal resuscitative efforts will typically be markedly improved following delivery with uterine decompression. Consequently we suggest that perimortem cesarean delivery be renamed "resuscitative hysterotomy" to reflect the mutual optimization of resuscitation efforts that would potentially provide earlier and more substantial benefit to both mother and baby. Copyright © 2015 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-01-01

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

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

Ma, C; Lin, M; Chen, L

Purpose: Recent in vitro and in vivo experimental findings provided strong evidence that pulsed low-dose-rate radiotherapy (PLDR) produced equivalent tumor control as conventional radiotherapy with significantly reduced normal tissue toxicities. This work aimed to implement a PLDR clinical protocol for the management of recurrent cancers utilizing IMRT and VMAT. Methods: Our PLDR protocol requires that the daily 2Gy dose be delivered in 0.2Gy×10 pulses with a 3min interval between the pulses. To take advantage of low-dose hyper-radiosensitivity the mean dose to the target is set at 0.2Gy and the maximum dose is limited to 0.4Gy per pulse. Practical planning strategiesmore » were developed for IMRT and VMAT: (1) set 10 ports for IMRT and 10 arcs for VMAT with each angle/arc as a pulse; (2) set the mean dose (0.2Gy) and maximum dose (0.4Gy) to the target per pulse as hard constraints (no constraints to OARs); (3) select optimal port/arc angles to avoid OARs; and (4) use reference structures in or around target/OARs to reduce maximum dose to the target/OARs. IMRT, VMAT and 3DCRT plans were generated for 60 H and N, breast, lung, pancreas and prostate patients and compared. Results: All PLDR treatment plans using IMRT and VMAT met the dosimetry requirements of the PLDR protocol (mean target dose: 0.20Gy±0.01Gy; maximum target dose < 0.4Gy). In comparison with 3DCRT, IMRT and VMAT exhibited improved target dose conformity and OAR dose sparing. A single arc can minimize the difference in the target dose due to multi-angle incidence although the delivery time is longer than 3DCRT and IMRT. Conclusion: IMRT and VMAT are better modalities for PLDR treatment of recurrent cancers with superior target dose conformity and critical structure sparing. The planning strategies/guidelines developed in this work are practical for IMRT/VMAT treatment planning to meet the dosimetry requirements of the PLDR protocol.« less

Optimizing the number of cleavage stage embryos to transfer on day 3 in women 38 years of age and older: a Society for Assisted Reproductive Technology database study.

PubMed

Stern, Judy E; Goldman, Marlene B; Hatasaka, Harry; MacKenzie, Todd A; Surrey, Eric S; Racowsky, Catherine

2009-03-01

To determine the optimal number of day 3 embryos to transfer in women >or=38 years by conducting an evidence-based evaluation. Retrospective analysis of 2000-2004 national SART data. National writing group. A total of 36,103 day 3 embryo transfers in women >or=38 years undergoing their first assisted reproductive technology cycle. None. Logistic regression was used to model the probability of pregnancy, delivery, and multiple births (twin or high order) based on age- and cycle-specific parameters. Pregnancy rates, delivery rates, and multiple rates increased up to transfer of three embryos in 38-year-olds and four in 39-year-olds; beyond this number, only multiple rates increased. In women >or=40 years, delivery rates and multiple rates climbed steadily with increasing numbers transferred. Multivariate analysis confirmed the statistically significant effect of age, number of oocytes retrieved, and embryo cryopreservation on delivery and multiple rates. Maximum FSH level was not an independent predictor by multivariate analysis. Use of intracytoplasmic sperm injection was associated with lowered delivery rate. No more than three or four embryos should be transferred in 38- and 39-year-olds, respectively, whereas up to five embryos could be transferred in >or=40-year-olds. Numbers of embryos to transfer should be adjusted according to number of oocytes retrieved and availability of excess embryos for cryopreservation.

Effective Targeted Gene Delivery to Dendritic Cells via Synergetic Interaction of Mannosylated Lipid with DOPE and BCAT

PubMed Central

Kim, Hee-Kwon; Wei, Huiling; Kulkarni, Aditya; Pogranichniy, Roman M.; Thompson, David H.

2012-01-01

The efficient delivery of plasmids encoding antigenic determinants into dendritic cells (DCs) that control immune response is a promising strategy for rapid development of new vaccines. In this study, we prepared a series of targeted cationic lipoplex based on two synthetic lipid components, mannose-poly(ethylene glycol, MW3000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (Mannose-PEG3000-DSPE) and O-(2R-1,2-di-O-(1'Z,9'Z-octadecadienyl)-glycerol)-3-N-(bis-2-aminoethyl)-carbamate (BCAT), that were formulated with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) for evaluation as non-viral vectors for transgene expression in DCs. First, we optimized the N:P ratio for maximum transfection and then screened the effects of mannose targeting for further enhancement of transfection levels. Our results indicate that efficient delivery of gWIZ GFP plasmid into DCs was observed for mannose compositions of ~10%, whereas low transfection efficiencies were observed with non-targeted formulations. Mannose-targeted lipofectamine complexes also showed high GFP expression levels in DCs relative to non-targeted lipofectamine controls. The best transfection performance was observed using 10 mol % Mannose-PEG3000-DSPE, 60 mol% BCAT, and 30 mol % DOPE, indicating that the most efficient delivery into DCs occurs via synergistic interaction between mannose targeting and acid-labile, fusogenic BCAT:DOPE formulations. Our data suggest that mannose-PEG3000-DSPE:BCAT:DOPE formulations may be effective gene delivery vehicles for the development of DC-based vaccines. PMID:22229467

Dystocia as a cause of untimely cesarean section.

PubMed

Djurić, Janko; Arsenijević, Slobodan; Banković, Dragic; Protrka, Zoran; Sorak, Marija; Dimitrijević, Aleksandra; Tanasković, Irena

2012-07-01

One of the most frequent indications for cesarean section is dystocia. It is impossible to predict, difficult to identify and coincident with the rapid expiry of the expected time, so it is important to point out some mistakes in expecting vaginal delivery. The aim of this study was to examine the frequency and the length of dystocia-related cesarean delivery, as well as the vitality of the newborn immediately after birth. A prospective 3-year study was conducted including a total number of 6470 deliveries regardless of whether they were completed using cesarean section after an unsuccessful attempt of spontaneous vaginal delivery or not. The Apgar score, a proved useful tool for the assessment of the vitality of newborn children in the first minute, was used. On the basis of the established indications, 653 (10.10%) of deliveries were completed using cesarean section. Dystocia was the third most common indication for cesarean section (16.38%). Deliveries in which dystocia was established as a diagnosis lasted much longer (p = 0.030) which resulted in weaker vitality of newborn children (p = 0.000) compared to the deliveries ended by spontaneous vaginal delivery. This study shows that deliveries caused by dystocia last much longer and newborn children are of weaker vitality compared to other deliveries caused not by dystocia. Decisions concerning cesarean section must be made in a timely fashion.

Comparison of Breast Crawl Between Infants Delivered by Vaginal Delivery and Cesarean Section.

PubMed

Heidarzadeh, Mohammad; Hakimi, Sevil; Habibelahi, Abbas; Mohammadi, Marzieh; Shahrak, Shakiba Pourasad

2016-05-12

Exclusive breastfeeding is the single most cost-effective intervention to reduce infant mortality. Breast crawl (BC) is deemed a natural way for the baby to behave immediately after delivery. BC is the method that may help initiation of breastfeeding in the most natural way. The aim of this study is to compare successful BC between neonates born through vaginal delivery and those born through cesarean section (CS) and factors associated with a positive outcome. Participants were mothers who delivered their babies during the period of October 2012 to December 2013 in Alzahra Hospital in Tabriz, through cesarean or vaginal delivery. Infants were placed prone on their mothers' abdomen after delivery. Data show that babies delivered through vaginal delivery had significantly more success in BC than babies born through the cesarean delivery (88.01% versus 11.21%). Moreover, babies in the CS group used significantly less time to achieve BC (45 versus 28 minutes). There is a remarkable difference in completion and length of time used to achieve BC between infants with regard to the delivery mode. Encouraging BC in all dyads, especially in cesarean births, may unduly delay the infant's first breastfeed.

41 CFR 301-31.10 - How will my agency pay my subsistence expenses?

Code of Federal Regulations, 2010 CFR

2010-07-01

... applicable to the locality .75 times the maximum lodging amount applicable to the locality .5 times the maximum lodging amount applicable to the locality. Payment for lodging, meals, and other per diem expenses The maximum per diem rate applicable to the locality .75 times the maximum per diem rate applicable to...

26 CFR 1.410(a)-4 - Maximum age conditions and time of participation.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 26 Internal Revenue 5 2012-04-01 2011-04-01 true Maximum age conditions and time of participation.... § 1.410(a)-4 Maximum age conditions and time of participation. (a) Maximum age conditions—(1) General...) if the plan excludes from participation (on the basis of age) an employee who has attained an age...

26 CFR 1.410(a)-4 - Maximum age conditions and time of participation.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 5 2011-04-01 2011-04-01 false Maximum age conditions and time of participation.... § 1.410(a)-4 Maximum age conditions and time of participation. (a) Maximum age conditions—(1) General...) if the plan excludes from participation (on the basis of age) an employee who has attained an age...

26 CFR 1.410(a)-4 - Maximum age conditions and time of participation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Maximum age conditions and time of participation... Maximum age conditions and time of participation. (a) Maximum age conditions—(1) General rule. A plan is... excludes from participation (on the basis of age) an employee who has attained an age specified by the plan...

Wavelet extractor: A Bayesian well-tie and wavelet extraction program

NASA Astrophysics Data System (ADS)

Gunning, James; Glinsky, Michael E.

2006-06-01

We introduce a new open-source toolkit for the well-tie or wavelet extraction problem of estimating seismic wavelets from seismic data, time-to-depth information, and well-log suites. The wavelet extraction model is formulated as a Bayesian inverse problem, and the software will simultaneously estimate wavelet coefficients, other parameters associated with uncertainty in the time-to-depth mapping, positioning errors in the seismic imaging, and useful amplitude-variation-with-offset (AVO) related parameters in multi-stack extractions. It is capable of multi-well, multi-stack extractions, and uses continuous seismic data-cube interpolation to cope with the problem of arbitrary well paths. Velocity constraints in the form of checkshot data, interpreted markers, and sonic logs are integrated in a natural way. The Bayesian formulation allows computation of full posterior uncertainties of the model parameters, and the important problem of the uncertain wavelet span is addressed uses a multi-model posterior developed from Bayesian model selection theory. The wavelet extraction tool is distributed as part of the Delivery seismic inversion toolkit. A simple log and seismic viewing tool is included in the distribution. The code is written in Java, and thus platform independent, but the Seismic Unix (SU) data model makes the inversion particularly suited to Unix/Linux environments. It is a natural companion piece of software to Delivery, having the capacity to produce maximum likelihood wavelet and noise estimates, but will also be of significant utility to practitioners wanting to produce wavelet estimates for other inversion codes or purposes. The generation of full parameter uncertainties is a crucial function for workers wishing to investigate questions of wavelet stability before proceeding to more advanced inversion studies.

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

Herrington, J; Price, M; Brindle, J

Purpose: To evaluate the equivalence of spine SBRT treatment plans created in Eclipse for the TrueBeam STx (Varian Medical System, Palo Alto, CA) compared to plans using CyberKnife and MultiPlan (Accuray, Sunnyvale, CA). Methods: CT data and contours for 23 spine SBRT patients previously treated using CyberKnife (CK) were exported from MultiPlan treatment planning system into Eclipse where they were planned using static IMRT 6MV coplanar beams. Plans were created according to the original prescription dose and fractionation schedule while limiting spinal dose according to the RTOG 0631 protocol and maintaining target coverage comparable to the original CK plans. Plansmore » were evaluated using new conformity index (nCI), homogeneity index (HI), dose-volume histogram data, number of MU, and estimated treatment time. To ensure all Eclipse plans were deliverable, standard clinical IMRT QA was performed. The plan results were matched with their complimentary CK plans for paired statistical analysis. Results: Plans generated in Eclipse demonstrated statistically significant (p<0.01) improvements compared to complimentary CK plans in median values of maximum spinal cord dose (17.39 vs. 18.12 Gy), RTOG spinal cord constraint dose (14.50 vs. 16.93 Gy), nCI (1.28 vs. 1.54), HI (1.13 vs. 1.27), MU (3918 vs. 36416), and estimated treatment time (8 vs. 48 min). All Eclipse generated plans passed our clinically used protocols for IMRT QA. Conclusion: CK spine SBRT replanned utilizing Eclipse for LINAC delivery demonstrated dosimetric advantages. We propose improvements in plan quality metrics reviewed in this study may be attributed to dynamic MLCs that facilitate treatment of complicated geometries as well as posterior beams ideal for centrally located and/or posterior targets afforded by gantry-based RT delivery.« less

Ground water stratification and delivery of nitrate to an incised stream under varying flow conditions.

PubMed

Böhlke, J K; O'Connell, Michael E; Prestegaard, Karen L

2007-01-01

Ground water processes affecting seasonal variations of surface water nitrate concentrations were investigated in an incised first-order stream in an agricultural watershed with a riparian forest in the coastal plain of Maryland. Aquifer characteristics including sediment stratigraphy, geochemistry, and hydraulic properties were examined in combination with chemical and isotopic analyses of ground water, macropore discharge, and stream water. The ground water flow system exhibits vertical stratification of hydraulic properties and redox conditions, with sub-horizontal boundaries that extend beneath the field and adjacent riparian forest. Below the minimum water table position, ground water age gradients indicate low recharge rates (2-5 cm yr(-1)) and long residence times (years to decades), whereas the transient ground water wedge between the maximum and minimum water table positions has a relatively short residence time (months to years), partly because of an upward increase in hydraulic conductivity. Oxygen reduction and denitrification in recharging ground waters are coupled with pyrite oxidation near the minimum water table elevation in a mottled weathering zone in Tertiary marine glauconitic sediments. The incised stream had high nitrate concentrations during high flow conditions when much of the ground water was transmitted rapidly across the riparian zone in a shallow oxic aquifer wedge with abundant outflow macropores, and low nitrate concentrations during low flow conditions when the oxic wedge was smaller and stream discharge was dominated by upwelling from the deeper denitrified parts of the aquifer. Results from this and similar studies illustrate the importance of near-stream geomorphology and subsurface geology as controls of riparian zone function and delivery of nitrate to streams in agricultural watersheds.

Ground water stratification and delivery of nitrate to an incised stream under varying flow conditions

USGS Publications Warehouse

Böhlke, J.K.; O'Connell, M. E.; Prestegaard, K.L.

2007-01-01

Ground water processes affecting seasonal variations of surface water nitrate concentrations were investigated in an incised first-order stream in an agricultural watershed with a riparian forest in the coastal plain of Maryland. Aquifer characteristics including sediment stratigraphy, geochemistry, and hydraulic properties were examined in combination with chemical and isotopic analyses of ground water, macropore discharge, and stream water. The ground water flow system exhibits vertical stratification of hydraulic properties and redox conditions, with sub-horizontal boundaries that extend beneath the field and adjacent riparian forest. Below the minimum water table position, ground water age gradients indicate low recharge rates (2-5 cm yr-1) and long residence times (years to decades), whereas the transient ground water wedge between the maximum and minimum water table positions has a relatively short residence time (months to years), partly because of an upward increase in hydraulic conductivity. Oxygen reduction and denitrification in recharging ground waters are coupled with pyrite oxidation near the minimum water table elevation in a mottled weathering zone in Tertiary marine glauconitic sediments. The incised stream had high nitrate concentrations during high flow conditions when much of the ground water was transmitted rapidly across the riparian zone in a shallow oxic aquifer wedge with abundant outflow macropores, and low nitrate concentrations during low flow conditions when the oxic wedge was smaller and stream discharge was dominated by upwelling from the deeper denitrified parts of the aquifer. Results from this and similar studies illustrate the importance of near-stream geomorphology and subsurface geology as controls of riparian zone function and delivery of nitrate to streams in agricultural watersheds. ?? ASA, CSSA, SSSA.

Adaptive radiation therapy for postprostatectomy patients using real-time electromagnetic target motion tracking during external beam radiation therapy.

PubMed

Zhu, Mingyao; Bharat, Shyam; Michalski, Jeff M; Gay, Hiram A; Hou, Wei-Hsien; Parikh, Parag J

2013-03-15

Using real-time electromagnetic (EM) transponder tracking data recorded by the Calypso 4D Localization System, we report inter- and intrafractional target motion of the prostate bed, describe a strategy to evaluate treatment adequacy in postprostatectomy patients receiving intensity modulated radiation therapy (IMRT), and propose an adaptive workflow. Tracking data recorded by Calypso EM transponders was analyzed for postprostatectomy patients that underwent step-and-shoot IMRT. Rigid target motion parameters during beam delivery were calculated from recorded transponder positions in 16 patients with rigid transponder geometry. The delivered doses to the clinical target volume (CTV) were estimated from the planned dose matrix and the target motion for the first 3, 5, 10, and all fractions. Treatment adequacy was determined by comparing the delivered minimum dose (Dmin) with the planned Dmin to the CTV. Treatments were considered adequate if the delivered CTV Dmin is at least 95% of the planned CTV Dmin. Translational target motion was minimal for all 16 patients (mean: 0.02 cm; range: -0.12 cm to 0.07 cm). Rotational motion was patient-specific, and maximum pitch, yaw, and roll were 12.2, 4.1, and 10.5°, respectively. We observed inadequate treatments in 5 patients. In these treatments, we observed greater target rotations along with large distances between the CTV centroid and transponder centroid. The treatment adequacy from the initial 10 fractions successfully predicted the overall adequacy in 4 of 5 inadequate treatments and 10 of 11 adequate treatments. Target rotational motion could cause underdosage to partial volume of the postprostatectomy targets. Our adaptive treatment strategy is applicable to post-prostatectomy patients receiving IMRT to evaluate and improve radiation therapy delivery. Copyright © 2013 Elsevier Inc. All rights reserved.

Maternal Buprenorphine Dose, Placenta Buprenorphine and Metabolite Concentrations and Neonatal Outcomes

PubMed Central

Concheiro, Marta; Jones, Hendreé E.; Johnson, Rolley E.; Choo, Robin; Shakleya, Diaa M.; Huestis, Marilyn A.

2010-01-01

Buprenorphine is approved as pharmacotherapy for opioid dependence in non-pregnant patients in multiple countries, and is currently under investigation for pregnant women in the US and Europe. This research evaluates the disposition of buprenorphine, opiates, cocaine, and metabolites in 5 term placentas from a US cohort. Placenta and matched meconium concentrations were compared, and relationships between maternal buprenorphine dose, placenta concentrations, and neonatal outcomes following controlled administration during gestation were investigated. Buprenorphine and/or metabolites were detected in all placenta specimens and were uniformly distributed across this tissue (CV<27.5%, 4 locations), except for buprenorphine in 3 placentas. In 2 of these, buprenorphine was not detected in some locations and, in the 3rd placenta, was totally absent. Median (range) concentrations were buprenorphine 1.6ng/g (not detected to 3.2), norbuprenorphine 14.9ng/g (6.2 to 24.2), buprenorphine-glucuronide 3ng/g (1.3 to 5.0) and norbuprenorphine-glucuronide 14.7ng/g (11.4 to 25.8). Placenta is a potential alternative matrix for detecting in utero buprenorphine exposure, but at lower concentrations (15–70 fold) than in meconium. Statistically significant correlations were observed for mean maternal daily dose from enrollment to delivery and placenta buprenorphine-glucuronide concentration, and for norbuprenorphine-glucuronide concentrations and time to neonatal abstinence syndrome (NAS) onset and duration, and for norbuprenorphine/norbuprenorphine-glucuronide ratio and maximum NAS score, and newborn length. Analysis of buprenorphine and metabolites in this alternative matrix, an abundant waste product available at the time of delivery, may be valuable for prediction of neonatal outcomes for clinicians treating newborns of buprenorphine-exposed women. PMID:20216119

Fast approximate delivery of fluence maps for IMRT and VMAT

NASA Astrophysics Data System (ADS)

Balvert, Marleen; Craft, David

2017-02-01

In this article we provide a method to generate the trade-off between delivery time and fluence map matching quality for dynamically delivered fluence maps. At the heart of our method lies a mathematical programming model that, for a given duration of delivery, optimizes leaf trajectories and dose rates such that the desired fluence map is reproduced as well as possible. We begin with the single fluence map case and then generalize the model and the solution technique to the delivery of sequential fluence maps. The resulting large-scale, non-convex optimization problem was solved using a heuristic approach. We test our method using a prostate case and a head and neck case, and present the resulting trade-off curves. Analysis of the leaf trajectories reveals that short time plans have larger leaf openings in general than longer delivery time plans. Our method allows one to explore the continuum of possibilities between coarse, large segment plans characteristic of direct aperture approaches and narrow field plans produced by sliding window approaches. Exposing this trade-off will allow for an informed choice between plan quality and solution time. Further research is required to speed up the optimization process to make this method clinically implementable.

The Preemptive Stocker Dispatching Rule of Automatic Material Handling System in 300 mm Semiconductor Manufacturing Factories

NASA Astrophysics Data System (ADS)

Wang, C. N.; Lin, H. S.; Hsu, H. P.; Wang, Yen-Hui; Chang, Y. P.

2016-04-01

The integrated circuit (IC) manufacturing industry is one of the biggest output industries in this century. The 300mm wafer fabs is the major fab size of this industry. The automatic material handling system (AMHS) has become one of the most concerned issues among semiconductor manufacturers. The major lot delivery of 300mm fabs is used overhead hoist transport (OHT). The traffic jams are happened frequently due to the wide variety of products and big amount of OHTs moving in the fabs. The purpose of this study is to enhance the delivery performance of automatic material handling and reduce the delay and waiting time of product transportation for both hot lots and normal lots. Therefore, this study proposes an effective OHT dispatching rule: preemptive stocker dispatching (PSD). Simulation experiments are conducted and one of the best differentiated preemptive rule, differentiated preemptive dispatching (DPD), is used for comparison. Compared with DPD, The results indicated that PSD rule can reduce average variable delivery time of normal lots by 13.15%, decreasing average variable delivery time of hot lots by 17.67%. Thus, the PSD rule can effectively reduce the delivery time and enhance productivity in 300 mm wafer fabs.

Design and optimization of a flexible high-peak-power laser-to-fiber coupled illumination system used in digital particle image velocimetry

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

Robinson, Ronald A.; Ilev, Ilko K.

We present a study on the design and parameter optimization of a flexible high-peak-power fiber-optic laser delivery system using commercially available solid-core silica fibers and an experimental glass hollow waveguide (HW). The fiber-optic delivery system provides a flexible, safe, and easily and precisely positioned laser irradiation for many applications including uniform illumination for digital particle image velocimetry (DPIV). The delivery fibers, when coupled through a line-generating lens, produce a uniform thin laser sheet illumination for accurate and repeatable DPIV two-dimensional velocity measurements. We report experimental results on homogenizing the laser beam profile using various mode-mixing techniques. Furthermore, because a fundamentalmore » problem for fiber-optic-based high-peak-power laser delivery systems is the possible damage effects of the fiber material, we determine experimentally the peak power density damage threshold of various delivery fibers designed for the visible spectral range at a typical DPIV laser wavelength of 532 nm. In the case of solid-core silica delivery fibers using conventional lens-based laser-to-fiber coupling, the damage threshold varies from 3.7 GW/cm{sup 2} for a 100-{mu}m-core-diameter high-temperature fiber to 3.9 GW/cm{sup 2} for a 200-{mu}m-core-diameter high-power delivery fiber, with a total output laser energy delivered of at least 3-10 mJ for those respective fibers. Therefore, these fibers are marginally suitable for most macro-DPIV applications. However, to improve the high-power delivery capability for close-up micro-DPIV applications, we propose and validate an experimental fiber link with much higher laser power delivery capability than the solid-core fiber links. We use an uncoated grazing-incidence-based tapered glass funnel coupled to a glass HW with hollow air-core diameter of 700 {mu}m, a low numerical aperture of 0.05, and a thin inside cladding of cyclic olefin polymer coating for optimum transmission at 532 nm. Because of the mode homogenizing effect and lower power density, the taper-waveguide laser delivery technique ensured high damage threshold for the delivery HW, and as a result, no damage occurred at the maximum measured input laser energy of 33 mJ used in this study.« less

Bishop score and ultrasound assessment of the cervix for prediction of time to onset of labor and time to delivery in prolonged pregnancy.

PubMed

Strobel, E; Sladkevicius, P; Rovas, L; De Smet, F; Karlsson, E Dejin; Valentin, L

2006-09-01

To determine the ability of Bishop score and sonographic cervical length to predict time to spontaneous onset of labor and time to delivery in prolonged pregnancy. Ninety-seven women underwent transvaginal ultrasound examination and palpation of the cervix at 291-296 days' gestation according to ultrasound fetometry at 12-20 weeks' gestation. Sonographic cervical length and Bishop score were recorded. Multivariate logistic regression analysis was used to determine which variables were independent predictors of the onset of labor/delivery < or = 24 h, < or = 48 h, and < or = 96 h. Receiver-operating characteristics (ROC) curves were drawn to assess diagnostic performance. In nulliparous women (n = 45), both Bishop score and sonographic cervical length predicted the onset of labor/delivery < or = 24 h and < or = 48 h (area under ROC curve for the onset of labor < or = 24 h 0.79 vs. 0.80, P = 0.94; for delivery < or = 24 h 0.81 vs. 0.85, P = 0.64; for the onset of labor < or = 48 h 0.73 vs. 0.74, P = 0.90; for delivery < or = 48 h 0.77 vs. 0.71, P = 0.50). Only Bishop score discriminated between nulliparous women who went into labor/delivered < or = 96 h or > 96 h. A logistic regression model including Bishop score and cervical length was superior to Bishop score alone in predicting delivery < or = 24 h (area under ROC curve 0.93 vs. 0.81, P = 0.03) and superior to Bishop score alone and cervical length alone in predicting the onset of labor < or = 24 h (area under ROC curve 0.90 vs. 0.79, P = 0.06; and 0.90 vs. 0.80, P = 0.06). In parous women (n = 52), Bishop score and sonographic cervical length predicted the onset of labor/delivery < or = 24 h (area under ROC curve for the onset of labor 0.75 vs. 0.69, P = 0.49; for delivery 0.74 vs. 0.70, P = 0.62), but only Bishop score discriminated between women who went into labor/delivered < or = 48 h and > 48 h. Three parous women had not gone into labor and six had not given birth at 96 h. In parous women logistic regression models including both Bishop score and cervical length did not substantially improve prediction of the time to onset of labor/delivery. In prolonged pregnancy Bishop score and sonographic cervical length have a similar ability to predict the time to the onset of labor and delivery. In nulliparous women the use of logistic regression models including Bishop score and cervical length is likely to offer better prediction of the onset of labor/delivery < or = 24 h than the use of the Bishop score alone. Copyright 2006 ISUOG. Published by John Wiley & Sons, Ltd.

Cavitation-enhanced delivery of a replicating oncolytic adenovirus to tumors using focused ultrasound.

PubMed

Bazan-Peregrino, Miriam; Rifai, Bassel; Carlisle, Robert C; Choi, James; Arvanitis, Costas D; Seymour, Leonard W; Coussios, Constantin C

2013-07-10

Oncolytic viruses (OV) and ultrasound-enhanced drug delivery are powerful novel technologies. OV selectively self-amplify and kill cancer cells but their clinical use has been restricted by limited delivery from the bloodstream into the tumor. Ultrasound has been previously exploited for targeted release of OV in vivo, but its use to induce cavitation, microbubble oscillations, for enhanced OV tumor extravasation and delivery has not been previously reported. By identifying and optimizing the underlying physical mechanism, this work demonstrates that focused ultrasound significantly enhances the delivery and biodistribution of systemically administered OV co-injected with microbubbles. Up to a fiftyfold increase in tumor transgene expression was achieved, without any observable tissue damage. Ultrasound exposure parameters were optimized as a function of tumor reperfusion time to sustain inertial cavitation, a type of microbubble activity, throughout the exposure. Passive detection of acoustic emissions during treatment confirmed inertial cavitation as the mechanism responsible for enhanced delivery and enabled real-time monitoring of successful viral delivery. Copyright © 2013 Elsevier B.V. All rights reserved.

Resolution of pain after childbirth.

PubMed

Eisenach, James C; Pan, Peter; Smiley, Richard M; Lavand'homme, Patricia; Landau, Ruth; Houle, Timothy T

2013-01-01

Chronic pain after surgery occurs in 10-40% of individuals, including 5-20% of women after cesarean delivery in previous reports. Pain and depression 2 months after childbirth are independently associated with more severe acute post-delivery pain. Here we examine other predictors of pain at 2 months and determine the incidence of pain at 6 and 12 months after childbirth. Following Institutional Review Board approval, 1228 women were interviewed within 36 h of delivery. Of these, 937 (76%) were successfully contacted by telephone at 2 months, and, if they had pain, at 6 and 12 months after delivery. The primary outcome measure was presence of pain which began at the time of delivery. We also generated a model of severity of acute post-delivery pain and 2 month pain and depression. Pain which began at the time of delivery was remarkably rare 6 and 12 months later (1.8% and 0.3% [upper 95% confidence limit, 1.2%], respectively). Past history of pain and degree of tissue damage at delivery accounted for 7.0% and 16.7%, respectively, of one aspect in the variability in acute post-delivery pain. Neither of these factors was associated with incidence of pain 2 months later. Using a definition of new onset pain from delivery, we show a remarkably low incidence of pain 1 yr after childbirth, including those with surgical delivery. Additionally, degree of tissue trauma and history of chronic pain, risk factors for pain 2 months after other surgery, were unimportant to pain 2 months after cesarean or vaginal delivery.

Nutraceutical delivery systems: resveratrol encapsulation in grape seed oil nanoemulsions formed by spontaneous emulsification.

PubMed

Davidov-Pardo, Gabriel; McClements, David Julian

2015-01-15

The aim of this work was to fabricate nanoemulsions-based delivery systems to encapsulate resveratrol. Nanoemulsions were formed using spontaneous emulsification method: 10% oil phase (grape seed oil plus orange oil) and 10% surfactant (Tween 80) were titrated into 80% aqueous phase. An optimum orange oil-to-grape seed oil ratio of 1:1(w/w) formed small droplets (d ≈ 100 nm) with good stability to droplet growth. The maximum amount of resveratrol that could be dissolved in the oil phase was 120 ± 10 μg/ml. The effect of droplet size on the chemical stability of encapsulated resveratrol was examined by preparing systems with different mean droplet diameters of 220 ± 2; 99 ± 3; and 45 ± 0.4 nm. Encapsulation of resveratrol improved its chemical stability after exposure to UV-light: 88% retention in nanoemulsions compared to 50% in dimethylsulphoxide (DMSO). This study showed that resveratrol could be encapsulated within low-energy nanoemulsion-based delivery systems and protected against degradation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Radiant{trademark} Liquid Radioisotope Intravascular Radiation Therapy System

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

Eigler, N.; Whiting, J.; Chernomorsky, A.

1998-01-16

RADIANT{trademark} is manufactured by United States Surgical Corporation, Vascular Therapies Division, (formerly Progressive Angioplasty Systems). The system comprises a liquid {beta}-radiation source, a shielded isolation/transfer device (ISAT), modified over-the-wire or rapid exchange delivery balloons, and accessory kits. The liquid {beta}-source is Rhenium-188 in the form of sodium perrhenate (NaReO{sub 4}), Rhenium-188 is primarily a {beta}-emitter with a physical half-life of 17.0 hours. The maximum energy of the {beta}-particles is 2.1 MeV. The source is produced daily in the nuclear pharmacy hot lab by eluting a Tungsten-188/Rhenium-188 generator manufactured by Oak Ridge National Laboratory (ORNL). Using anion exchange columns and Milliporemore » filters the effluent is concentrated to approximately 100 mCi/ml, calibrated, and loaded into the (ISAT) which is subsequently transported to the cardiac catheterization laboratory. The delivery catheters are modified Champion{trademark} over-the-wire, and TNT{trademark} rapid exchange stent delivery balloons. These balloons have thickened polyethylene walls to augment puncture resistance; dual radio-opaque markers and specially configured connectors.« less

Development of a Fiber-Optics Microspatially Offset Raman Spectroscopy Sensor for Probing Layered Materials.

PubMed

Vandenabeele, Peter; Conti, Claudia; Rousaki, Anastasia; Moens, Luc; Realini, Marco; Matousek, Pavel

2017-09-05

Microspatially offset Raman spectroscopy (micro-SORS) has been proposed as a valuable approach to sample molecular information from layers that are covered by a turbid (nontransparent) layer. However, when large magnifications are involved, the approach is not straightforward, as spatial constraints exist to position the laser beam and the objective lens with the external beam delivery or, with internal beam delivery, the maximum spatial offset achievable is restricted. To overcome these limitations, we propose here a prototype of a new micro-SORS sensor, which uses bare glass fibers to transfer the laser radiation to the sample and to collect the Raman signal from a spatially offset zone to the Raman spectrometer. The concept also renders itself amenable to remote delivery and to the miniaturization of the probe head which could be beneficial for special applications, e.g., where access to sample areas is restricted. The basic applicability of this approach was demonstrated by studying several layered structure systems. Apart from proving the feasibility of the technique, also, practical aspects of the use of the prototype sensor are discussed.

Sediment tracing by `customised' magnetic fingerprinting: from the sub-catchment to the ocean scale

NASA Astrophysics Data System (ADS)

Maher, B.

2009-04-01

Robust identification of catchment suspended sediment sources is a prerequisite both for understanding sediment delivery processes and targeting of effective mitigation measures. Fine sediment delivery can pose management problems, especially with regard to nutrient run-off and siltation of water courses and bodies. Suspended sediment load constitutes the dominant mode of particulate material loss from catchments but its transport is highly episodic. Identification of suspended sediment sources and fluxes is therefore a prerequisite both for understanding of fluvial geomorphic process and systems and for designing strategies to reduce sediment transport, delivery and yields. Here will be discussed sediment ‘fingerprinting', using the magnetic properties of soils and sediments to characterise sediment sources and transport pathways over a very wide variety of spatial scales, from Lake Bassenthwaite in the English Lake District to the Burdekin River in Queensland and even the North Atlantic Ocean during the last glacial maximum. The applicability of magnetic ‘fingerprinting' to such a range of scales and environments has been significantly improved recently through use of new and site-appropriate magnetic measurement techniques, statistical processing and sample treatment options.

The Impact of Biomass Feedstock Supply Variability on the Delivered Price to a Biorefinery in the Peace River Region of Alberta, Canada

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

Stephen, Jamie; Sokhansanj, Shahabaddine; Bi, X.T.

2010-01-01

Agricultural residue feedstock availability in a given region can vary significantly over the 20 25 year lifetime of a biorefinery. Since delivered price of biomass feedstock to a biorefinery is related to the distance travelled and equipment optimization, and transportation distance increases as productivity decreases, productivity is a primary determinant of feedstock price. Using the Integrated Biomass Supply Analysis and Logistics (IBSAL) modeling environment and a standard round bale harvest and delivery scenario, harvest and delivery price were modelled for minimum, average, and maximum yields at four potential biorefinery sites in the Peace River region of Alberta, Canada. Biorefinery capacitiesmore » ranged from 50,000 to 500,000 tonnes per year. Delivery cost is a linear function of transportation distance and can be combined with a polynomial harvest function to create a generalized delivered cost function for agricultural residues. The range in delivered cost is substantial and is an important consideration for the operating costs of a biorefinery.« less

Sustained versus intermittent lung inflation for resuscitation of preterm infants: a randomized controlled trial.

PubMed

El-Chimi, Mohamed S; Awad, Hisham A; El-Gammasy, Tarek M; El-Farghali, Ola G; Sallam, Mohamed T; Shinkar, Dina M

2017-06-01

To evaluate efficacy and safety of delivery room (DR) sustained lung inflation (SLI) in resuscitation of preterm neonates. Randomized Controlled Trial including 112 preterm infants randomized to either SLI (n = 57) using T-piece resuscitator [maximum three inflations with maximum pressure of 30 cmH 2 O for 15 s followed by continuous positive airway pressure (CPAP) of 5-7 cmH 2 O] or conventional bag/mask inflation (CBMI) (n = 55) using traditional self-inflating bag (maximum pressure of 40 cmH 2 O at a rate of 40-60 per min). Failure was defined as the need for DR or first 72 h intubation. Cord and 2-h post-resuscitation blood samples were collected to measure interleukin (IL)-1β and tumor necrosis factor-α levels before and after intervention. SLI was associated with significantly higher success rate compared to CBMI [75.4 versus 54.5%; p = 0.017], lower need for DR intubation [5.3% versus 23.6%; (X 2  =   7.7; p = 0.005)], higher 5-min-Apgar score (median 8 versus 7; p = 0.018), shorter duration on nasal-CPAP (p = 0.017), and non-significantly different air leak (7% versus 11%; p = 0.3) and bronchopulmonary dysplasia rates among survivors (2% versus 11%; p = 0.09). Post-resuscitation IL-1β plasma levels increased significantly in CBMI (p = 0.009) and not in SLI group. Delivery room SLI is more effective than intermittent bag and mask inflation for improving short-term respiratory outcome in preterm infants, without significant adverse effects.

Case mix adjusted variation in cesarean section rate in Sweden.

PubMed

Mesterton, Johan; Ladfors, Lars; Ekenberg Abreu, Anna; Lindgren, Peter; Saltvedt, Sissel; Weichselbraun, Marianne; Amer-Wåhlin, Isis

2017-05-01

Cesarean section (CS) rate is a well-established indicator of performance in maternity care and is also related to resource use. Case mix adjustment of CS rates when performing comparisons between hospitals is important. The objective of this study was to estimate case mix adjusted variation in CS rate between hospitals in Sweden. In total, 139 756 deliveries in 2011 and 2012 were identified in administrative systems in seven regions covering 67% of all deliveries in Sweden. Data were linked to the Medical birth register and population data. Twenty-three different sociodemographic and clinical characteristics were used for adjustment. Analyses were performed for the entire study population as well as for two subgroups. Logistic regression was used to analyze differences between hospitals. The overall CS rate was 16.9% (hospital minimum-maximum 12.1-22.6%). Significant variations in CS rate between hospitals were observed after case mix adjustment: hospital odds ratios for CS varied from 0.62 (95% CI 0.53-0.73) to 1.45 (95% CI 1.37-1.52). In nulliparous, cephalic, full-term, singletons the overall CS rate was 14.3% (hospital minimum-maximum: 9.0-19.0%), whereas it was 4.7% for multiparous, cephalic, full-term, singletons with no previous CS (hospital minimum-maximum: 3.2-6.7%). In both subgroups significant variations were observed in case mix adjusted CS rates. Significant differences in CS rate between Swedish hospitals were found after adjusting for differences in case mix. This indicates a potential for fewer interventions and lower resource use in Swedish childbirth care. Best practice sharing and continuous monitoring are important tools for improving childbirth care. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

Novel electric power-driven hydrodynamic injection system for gene delivery: safety and efficacy of human factor IX delivery in rats.

PubMed

Yokoo, T; Kamimura, K; Suda, T; Kanefuji, T; Oda, M; Zhang, G; Liu, D; Aoyagi, Y

2013-08-01

The development of a safe and reproducible gene delivery system is an essential step toward the clinical application of the hydrodynamic gene delivery (HGD) method. For this purpose, we have developed a novel electric power-driven injection system called the HydroJector-EM, which can replicate various time-pressure curves preloaded into the computer program before injection. The assessment of the reproducibility and safety of gene delivery system in vitro and in vivo demonstrated the precise replication of intravascular time-pressure curves and the reproducibility of gene delivery efficiency. The highest level of luciferase expression (272 pg luciferase per mg of proteins) was achieved safely using the time-pressure curve, which reaches 30 mm Hg in 10 s among various curves tested. Using this curve, the sustained expression of a therapeutic level of human factor IX protein (>500 ng ml(-1)) was maintained for 2 months after the HGD of the pBS-HCRHP-FIXIA plasmid. Other than a transient increase in liver enzymes that recovered in a few days, no adverse events were seen in rats. These results confirm the effectiveness of the HydroJector-EM for reproducible gene delivery and demonstrate that long-term therapeutic gene expression can be achieved by automatic computer-controlled hydrodynamic injection that can be performed by anyone.

North Pacific atmospheric rivers and their influence on western North America at the Last Glacial Maximum

NASA Astrophysics Data System (ADS)

Lora, Juan M.; Mitchell, Jonathan L.; Risi, Camille; Tripati, Aradhna E.

2017-01-01

Southwestern North America was wetter than present during the Last Glacial Maximum. The causes of increased water availability have been recently debated, and quantitative precipitation reconstructions have been underutilized in model-data comparisons. We investigate the climatological response of North Pacific atmospheric rivers to the glacial climate using model simulations and paleoclimate reconstructions. Atmospheric moisture transport due to these features shifted toward the southeast relative to modern. Enhanced southwesterly moisture delivery between Hawaii and California increased precipitation in the southwest while decreasing it in the Pacific Northwest, in agreement with reconstructions. Coupled climate models that are best able to reproduce reconstructed precipitation changes simulate decreases in sea level pressure across the eastern North Pacific and show the strongest southeastward shifts of moisture transport relative to a modern climate. Precipitation increases of ˜1 mm d-1, due largely to atmospheric rivers, are of the right magnitude to account for reconstructed pluvial conditions in parts of southwestern North America during the Last Glacial Maximum.

Out-of-pocket expenditure on institutional delivery in India.

PubMed

Mohanty, Sanjay K; Srivastava, Akanksha

2013-05-01

Though promotion of institutional delivery is used as a strategy to reduce maternal and neonatal mortality, about half of the deliveries in India are conducted at home without any medical care. Among women who deliver at home, one in four cites cost as barrier to facility-based care. The relative share of deliveries in private health centres has increased over time and the associated costs are often catastrophic for poor households. Though research has identified socio-economic, demographic and geographic barriers to the utilization of maternal care, little is known on the cost differentials in delivery care in India. The objective of this paper is to understand the regional pattern and socio-economic differentials in out-of-pocket (OOP) expenditure on institutional delivery by source of provider in India. The study utilizes unit data from the District Level Household and Facility Survey (DLHS-3), conducted in India during 2007-08. Descriptive statistics, principal component analyses and a two-part model are used in the analyses. During 2004-08, the mean OOP expenditure for a delivery in a public health centre in India was US$39 compared with US$139 in a private health centre. The predicted expenditure for a caesarean delivery was six times higher than for a normal delivery. With an increase in the economic status and educational attainment of mothers, the propensity and rate of OOP expenditure increases, linking higher OOP expenditure to quality of care. The OOP expenditure in public health centres, adjusting for inflation, has declined over time, possibly due to increased spending under the National Rural Health Mission. Based on these findings, we recommend that facilities in public health centres of poorly performing states are improved and that public-private partnership models are developed to reduce the economic burden for households of maternal care in India.

Asteroid and comet impacts on Mars and their influence on atmospheric mass evolution and habitability.

NASA Astrophysics Data System (ADS)

Karatekin, Özgür

2015-04-01

Impacts by asteroids and comets could have significant affects on the habitability and atmospheric evolution of terrestrial planets by removing part of its atmosphere, by delivering into it material and volatiles. Large impacts could have repeatedly destroyed the existing biosphere, but in the mean time new subsurface habitats have likely formed from impact induced hydrothermal systems. Early in its history, Mars could have a much denser atmosphere and higher surface temperatures to sustain the presence of stable liquid water or saline solution at the surface, as suggested by several studies. The environmental effects of a period of impact bombardment on terrestrial planets remain poorly constrained. In this study we revisit the atmospheric loss and delivery of volatiles on Mars between the end of the Noachian and present using numerical models. Following an impact, the quantity of escaped atmosphere, as well as impactor and target materials can be estimated using numerical simulations. Studies on the atmospheric loss and delivery due to impacts differ sometimes by orders of magnitude, mainly due to different equation of state and dynamical models used. The hydrocode simulations designed to simulate a single impact are not suitable to study the cumulative effect of impact erosion and delivery in the long term due to their extremely high computation costs. Instead, empirical approximations based on hydrocode simulations have been used to estimate atmospheric evolution. Comparison between different hydrocode results and atmospheric mass evolution upon impacts based on empirical models will be presented using revised model parameters. In addition, different delivery and lost mechanisms including volcanic outgassing and non-thermal escape, can be taken into account to study various atmospheric evolution scenarios. Our results suggest that impacts alone can hardly remove a significant amount of atmospheric mass over this period. Contribution of additional factors such as outgassing and non- thermal escape processes can not explain neither the presence of surface pressure larger than few hundreds of mbars 3.9 Gyr ago. Based on extreme case scenarios, maximum surface pressures at the end of the Noachian, could be as much as 0.25 bar or 1.9 bar, with and without CO2 storage into carbonate reservoirs, respectively.

Parametric Imaging Of Digital Subtraction Angiography Studies For Renal Transplant Evaluation

NASA Astrophysics Data System (ADS)

Gallagher, Joe H.; Meaney, Thomas F.; Flechner, Stuart M.; Novick, Andrew C.; Buonocore, Edward

1981-11-01

A noninvasive method for diagnosing acute tubular necrosis and rejection would be an important tool for the management of renal transplant patients. From a sequence of digital subtraction angiographic images acquired after an intravenous injection of radiographic contrast material, the parametric images of the maximum contrast, the time when the maximum contrast is reached, and two times the time at which one half of the maximum contrast is reached are computed. The parametric images of the time when the maximum is reached clearly distinguish normal from abnormal renal function. However, it is the parametric image of two times the time when one half of the maximum is reached which provides some assistance in differentiating acute tubular necrosis from rejection.

Factors associated with delivery at home in Bhutan: findings from the National Health Survey 2012.

PubMed

Gurung, Mongal Singh; Pelzom, Dorji; Wangdi, Sonam; Tshomo, Tashi; Lethro, Pema; Dema, Tashi

2018-04-01

Despite Bhutan's remarkable progress in the area of maternal and child health during the era of the Millennium Development Goals, a large proportion of pregnant women are still delivering at home with no skilled attendant. Limited empirical studies have been carried out to understand the factors associated with delivery at home in Bhutan. This cross-sectional analytical study used secondary data collected in the nationally representative National Health Survey 2012. The survey included a total of 2213 women aged 15-49 years who had a live birth in the 2 years preceding the survey and were selected using multistage stratified cluster sampling. Weighted analysis was done to evaluate determinants for the place of delivery. Unadjusted and adjusted prevalence ratios with 95% confidence intervals (CIs) were calculated to assess the possible association of factors with home delivery. Out of 2213 women aged 15-49 years who had a live birth in the 2 years preceding the survey, 73.7% had an institutional delivery. Coverage of institutional delivery ranged from 49.4% in Zhemgang district to 96.1% in Paro district. Women in the poorest wealth quintile were 7.35 times more likely to have a birth at home compared to women in the richest quintile (adjusted prevalence ratio [aPR]: 7.35, 95% CI: 2.59-20.9). The older mothers aged 30-49 years were 0.79 times (aPR: 0.79, 95% CI: 0.70-0.88) less likely to have a home delivery than mothers aged 15-19 years. Women who had fewer than four antenatal care visits were 1.50 times (aPR: 1.50, 95% CI: 1.35-1.66) more likely to give birth at home compared to those who had four or more visits. The mothers giving birth for a third or more time were 1.88 times (aPR: 1.88, 95% CI: 1.60-2.22) more likely to give birth at home compared to those giving birth for the first time. Women living in rural areas were 2.87 times (aPR: 2.87, 95% CI: 1.42-5.77) more likely to deliver at home compared to those living in urban areas and women living in the eastern region of the country were 1.35 times (aPR: 1.35, 95% CI: 1.17-1.55) more likely to have a home delivery compared to those living in the western region. Lower socioeconomic status, rural location, eastern location, non- first birth, and having fewer than four antenatal visits were significant factors associated with home delivery. These findings should inform further research and policy to build on Bhutan's progress in promoting institutional delivery as the key strategy towards improving maternal and child health and achieving the relevant targets of Sustainable Development Goal 3.

MO-FG-202-03: Efficient Data Collection of Continuous 2D and Discrete Relative Dosimetric Data for Annual LINAC QA Using TrueBeam Developer Mode and a 1D Scanning Tank

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

Knutson, N; Schmidt, M; University of Rhode Island, Kingston, RI

2016-06-15

Purpose: To develop a method to exploit real-time dynamic machine and couch parameter control during linear accelerator (LINAC) beam delivery to facilitate efficient performance of TG-142 suggested, Annual LINAC QA tests. Methods: Varian’s TrueBeam Developer Mode (Varian Medical Systems, Palo Alto, CA) facilitates control of Varian’s TrueBeam LINAC via instructions provided in Extensible Markup Language (XML) files. This allows machine and couch parameters to be varied dynamically, in real-time, during beam delivery. Custom XML files were created to allow for the collection of (1) continuous Tissue Maximum Ratios (TMRs), (2) beam profiles, and (3) continuous output factors using a 1D-scanningmore » tank. TMRs were acquired by orienting an ionization chamber (IC) at isocenter (depth=25cm) and synchronizing a depth scan towards the water surface while lowering the couch at 1mm/s. For beam profiles, the couch was driven laterally and longitudinally while logging IC electrometer readings. Output factors (OFs) where collected by continually varying field sizes (4×4 to 30×30-cm{sup 2}) at a constant speed of 6.66 mm/s. To validate measurements, comparisons were made to data collected using traditional methods (e.g. 1D or 3D tank). Results: All data collecting using the proposed methods agreed with traditionally collected data (TMRs within 1%, OFs within 0.5% and beam profile agreement within 1% / 1mm) while taking less time to collect (factor of approximately 1/10) and with a finer sample resolution. Conclusion: TrueBeam developer mode facilitates collection of continuous data with the same accuracy as traditionally collected data with a finer resolution in less time. Results demonstrate an order of magnitude increase in sampled resolution and an order of magnitude reduction in collection time compared to traditional acquisition methods (e.g. 3D scanning tank). We are currently extending this approach to perform other TG-142 tasks.« less

Laser-assisted delivery of synergistic combination chemotherapy in in vivo skin.

PubMed

Wenande, Emily; Tam, Joshua; Bhayana, Brijesh; Schlosser, Steven Kyle; Ishak, Emily; Farinelli, William A; Chlopik, Agata; Hoang, Mai P; Pinkhasov, Omar R; Caravan, Peter; Rox Anderson, R; Haedersdal, Merete

2018-04-10

The effectiveness of topical drugs for treatment of non-melanoma skin cancer is greatly reduced by insufficient penetration to deep skin layers. Ablative fractional lasers (AFLs) are known to enhance topical drug uptake by generating narrow microchannels through the skin, but information on AFL-drug delivery in in vivo conditions is limited. In this study, we examined pharmacokinetics, biodistribution and toxicity of two synergistic chemotherapy agents, cisplatin and 5-fluorouracil (5-FU), following AFL-assisted delivery alone or in combination in in vivo porcine skin. Detected at 0-120 h using mass spectrometry techniques, we demonstrated that fractional CO 2 laser pretreatment (196 microchannels/cm 2 , 852 μm ablation depth) leads to rapid drug uptake in 1500 μm deep skin layers, with a sixfold enhancement in peak cisplatin concentrations versus non-laser-treated controls (5 h, P = 0.005). Similarly, maximum 5-FU deposition was measured within an hour of AFL-delivery, and exceeded peak deposition in non-laser-exposed skin that had undergone topical drug exposure for 5 days. Overall, this accelerated and deeper cutaneous drug uptake resulted in significantly increased inflammatory and histopathological effects. Based on clinical scores and transepidermal water loss measurement, AFL intensified local toxic responses to drugs delivered alone and in combination, while systemic drug exposure remained undetectable. Quantitative histopathologic analyses correspondingly revealed significantly reduced epidermal proliferation and greater cellular apoptosis after AFL-drug delivery; particularly after combined cisplatin + 5-FU exposure. In sum, by overcoming the primary limitation of topical drug penetration and providing accelerated, enhanced and deeper delivery, AFL-assisted combination chemotherapy may represent a promising treatment strategy for non-melanoma skin cancer. Copyright © 2018 Elsevier B.V. All rights reserved.

A self-powered kinesin-microtubule system for smart cargo delivery

NASA Astrophysics Data System (ADS)

Jia, Yi; Dong, Weiguang; Feng, Xiyun; Li, Jieling; Li, Junbai

2014-11-01

A smart self-powered cargo delivery system that is composed of creatine phosphate kinase (CPK) microspheres, kinesins and microtubules is demonstrated. The CPK microsphere not only acts as an ATP generation and buffering system, but also as a carrier for cargo transport, thus realizing the easy loading and self-powered delivery of cargos at the same time.A smart self-powered cargo delivery system that is composed of creatine phosphate kinase (CPK) microspheres, kinesins and microtubules is demonstrated. The CPK microsphere not only acts as an ATP generation and buffering system, but also as a carrier for cargo transport, thus realizing the easy loading and self-powered delivery of cargos at the same time. Electronic supplementary information (ESI) available: Experimental details, Fig. S1-S4, and Mov. S1-S6. See DOI: 10.1039/c4nr04454a

[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.

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.

10 Gbps Shuttle-to-Ground Adjunct Communication Link Capability Experiment

NASA Technical Reports Server (NTRS)

Ceniceros, J. M.; Sandusky, J. V.; Hemmati, H.

1999-01-01

A 1.2 Gbps space-to-ground laser communication experiment being developed for use on an EXpedite the PRocessing of Experiments to the Space Station (EXPRESS) Pallet Adapter can be adapted to fit the Hitchhiker cross-bay-carrier pallet and upgraded to data rates exceeding 1O Gbps. So modified, this instrument would enable both real-time data delivery and increased data volume for payloads using the Space Shuttle. Applications such as synthetic aperture radar and multispectral imaging collect large data volumes at a high rate and would benefit from the capability for real-time data delivery and from increased data downlink volume. Current shuttle downlink capability is limited to 50 Mbps, forcing such instruments to store large amounts of data for later analysis. While the technology is not yet sufficiently proven to be relied on as the primary communication link, when in view of the ground station it would increase the shuttle downlink rate capability 200 times, with typical total daily downlinks of 200 GB - as much data as the shuttle could downlink if it were able to maintain its maximum data rate continuously for one day. The lasercomm experiment, the Optical Communication Demonstration and High-Rate Link Facility (OCDHRLF), is being developed by the Jet Propulsion Laboratory's (JPL) Optical Communication Group through support from the International Space Station Engineering Research and Technology Development program. It is designed to work in conjunction with the Optical Communication Telescope Laboratory (OCTL) NASA's first optical communication ground station, which is under construction at JPL's Table Mountain Facility near Wrightwood, California. This paper discusses the modifications to the preliminary design of the flight system that would be necessary to adapt it to fit the Hitchhiker Cross-Bay Carrier. It also discusses orbit geometries which are favorable to the OCTL and potential non-NASA ground stations, anticipated burst-error-rates and bit-error-rates, and requirements for data collection on the ground.

Time and tide: examining the potential for sediment delivery to a heavily modified tidal delta plain

NASA Astrophysics Data System (ADS)

Hale, R. P.; Goodbred, S. L., Jr.; Bain, R. L.; Wilson, C.

2016-02-01

In SW Bangladesh, man-made barriers ("polders") built since the 1960s to protect agricultural resources from seasonal flooding have drastically altered delta-plain dynamics. With the link between tidal channels and the delta plain destroyed and no pathway for the delivery of new sediment, compaction, tectonic subsidence, and global sea-level rise have resulted in a scenario where much of the land surface behind the barriers sits 1.5 m below mean sea level. In the adjacent the Sundarbans National Forest (SNF), the lack of polders has allowed for sediment deposition during spring high tides, and sedimentation rates on the delta plain have kept pace with local sea level rise. Recent research has demonstrated the potential for rapid sedimentation in the inhabited areas following polder damage or destruction (Auerbach et al., 2015). These authors observed 40 cm/yr accumulation rates inside the poldered area following bank failures associated with a typhoon, and no obvious seasonality associated with the deposits. Preliminary research from within SNF, however, suggests that the accumulation rates are slightly faster during then monsoon (1.0-2.0 cm/yr) than the dry season (0.2-1.4 cm/yr). In this study, we address seasonal differences through a comparison of tidal elevations and suspended sediment concentrations (SSC) across tidal ranges and seasons, in both the SNF, and the tidal channels adjacent to the poldered region (PR). Water velocity appears to be the primary control on SSC, and there is no obvious seasonal variability in maximum observed SSC (PR: 0.1-0.8 g/l; SNF: 0.01-0.35 g/l). Peak tidal elevations remain unchanged across seasons, however the time of delta plain inundation time increases during the monsoon, which might control seasonal accumulation rates. Understanding more about this seasonal variability will be critical for future engineering and policy decisions surrounding how to best mitigate and manage land loss in the PR going forward.

Risk factors for failed reactivation of a labor epidural for postpartum tubal ligation: a prospective, observational study.

PubMed

Powell, Mark F; Wellons, Douglas D; Tran, Steve F; Zimmerman, John M; Frölich, Michael A

2016-12-01

To determine specific risk factors that increase the failure rate of labor epidurals reactivated for use as a surgical block for postpartum tubal ligation. Prospective, observational study. Labor and delivery suite and operating rooms at the Women and Infants Center. One hundred patients undergoing postpartum tubal ligation with an existing labor epidural that is documented to be within 2 cm of initial placement. Body mass index, patient satisfaction with her epidural during labor and delivery, time from delivery to reactivation for tubal ligation, depth to loss of resistance, and the need for top-ups during labor were recorded preoperatively. Failure to reactivate was recorded and defined as any patient that (1) did not achieve a T 6 level to pinprick, (2) had perceived pain (pain score >3) that required administration of an intravenous opioid or local anesthetic infiltration, or (3) required conversion to general anesthesia. The overall success rate of reactivation was 78%. Significant risk factors for failure to reactivate were (1) poor patient satisfaction (P = .016), (2) increased time from delivery to reactivation (P = .044), and (3) the need for top-ups during labor and delivery (P = .032). Poor satisfaction score of the epidural during labor and delivery, increasing time from delivery to epidural reactivation for tubal ligation, and the need for top-ups during labor and delivery increase the incidence of reactivation failure. No correlation was found with body mass index or loss of resistance and failure to reactivate. Copyright © 2016 Elsevier Inc. All rights reserved.

Employment during pregnancy and obstetric intervention without medical reason: labor induction and cesarean delivery.

PubMed

Kozhimannil, Katy Backes; Attanasio, Laura B; Johnson, Pamela Jo; Gjerdingen, Dwenda K; McGovern, Patricia M

2014-01-01

Rising rates of labor induction and cesarean delivery, especially when used without a medical reason, have generated concern among clinicians, women, and policymakers. Whether employment status affects pregnant women's childbirth-related care is not known. We estimated the relationship between prenatal employment and obstetric procedures, distinguishing whether women reported that the induction or cesarean was performed for medical reasons. Using data from a nationally representative sample of women who gave birth in U.S. hospitals (n = 1,573), we used propensity score matching to reduce potential bias from nonrandom selection into employment. Outcomes were cesarean delivery and labor induction, with and without a self-reported medical reason. Exposure was prenatal employment status (full-time employment, not employed). We conducted separate analyses for unmatched and matched cohorts using multivariable regression models. There were no differences in labor induction based on employment status. In unmatched analyses, employed women had higher odds of cesarean delivery overall (adjusted odds ratio [AOR], 1.45; p = .046) and cesarean delivery without medical reason (AOR, 1.94; p = .024). Adding an interaction term between employment and college education revealed no effects on cesarean delivery without medical reason. There were no differences in cesarean delivery by employment status in the propensity score-matched analysis. Full-time prenatal employment is associated with higher odds of cesarean delivery, but this association was not explained by socioeconomic status and no longer existed after accounting for sociodemographic differences by matching women employed full time with similar women not employed during pregnancy. Copyright © 2014 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

Experimental investigation of a moving averaging algorithm for motion perpendicular to the leaf travel direction in dynamic MLC target tracking.

PubMed

Yoon, Jai-Woong; Sawant, Amit; Suh, Yelin; Cho, Byung-Chul; Suh, Tae-Suk; Keall, Paul

2011-07-01

In dynamic multileaf collimator (MLC) motion tracking with complex intensity-modulated radiation therapy (IMRT) fields, target motion perpendicular to the MLC leaf travel direction can cause beam holds, which increase beam delivery time by up to a factor of 4. As a means to balance delivery efficiency and accuracy, a moving average algorithm was incorporated into a dynamic MLC motion tracking system (i.e., moving average tracking) to account for target motion perpendicular to the MLC leaf travel direction. The experimental investigation of the moving average algorithm compared with real-time tracking and no compensation beam delivery is described. The properties of the moving average algorithm were measured and compared with those of real-time tracking (dynamic MLC motion tracking accounting for both target motion parallel and perpendicular to the leaf travel direction) and no compensation beam delivery. The algorithm was investigated using a synthetic motion trace with a baseline drift and four patient-measured 3D tumor motion traces representing regular and irregular motions with varying baseline drifts. Each motion trace was reproduced by a moving platform. The delivery efficiency, geometric accuracy, and dosimetric accuracy were evaluated for conformal, step-and-shoot IMRT, and dynamic sliding window IMRT treatment plans using the synthetic and patient motion traces. The dosimetric accuracy was quantified via a tgamma-test with a 3%/3 mm criterion. The delivery efficiency ranged from 89 to 100% for moving average tracking, 26%-100% for real-time tracking, and 100% (by definition) for no compensation. The root-mean-square geometric error ranged from 3.2 to 4.0 mm for moving average tracking, 0.7-1.1 mm for real-time tracking, and 3.7-7.2 mm for no compensation. The percentage of dosimetric points failing the gamma-test ranged from 4 to 30% for moving average tracking, 0%-23% for real-time tracking, and 10%-47% for no compensation. The delivery efficiency of moving average tracking was up to four times higher than that of real-time tracking and approached the efficiency of no compensation for all cases. The geometric accuracy and dosimetric accuracy of the moving average algorithm was between real-time tracking and no compensation, approximately half the percentage of dosimetric points failing the gamma-test compared with no compensation.

Job Order Contracting: A Procurement Success Story

DTIC Science & Technology

1988-02-01

Engineering/Procurement processing time 279 CI4 TABLE C-2 JOC DELIVERY ORDER PROCESSING TIME Contract size and location Amount Elapsed time- ($000) days...Bragg 2.1 68 Monroe 2.1 196 Sill 2.2 3 bragg 2.3 32 C-5 Ii ~A¶A~.AL&A .LiA..hLI TABLE C-2 JOC DELIVERY ORDER PROCESSING TIME (Continued) Conrat szean...DEUVERY ORDER PROCESSING TIME (Continued) Amount Elapsed time- Contract size and location Amou daps($000) days Bragg S 14.7 11 Monroe 14.8 30 Monroe

Dynamic pushing on three frictional surfaces: maximum acceptable forces, cardiopulmonary and calf muscle metabolic responses in healthy men.

PubMed

Maikala, Rammohan V; Dempsey, Patrick G; Ciriello, Vincent M; O'Brien, Niall V

2009-06-01

Pushing is an important materials handling activity in many occupations; however, pushing-related physiological investigations are still in infancy. The purpose was to evaluate maximum acceptable forces and physiological responses while pushing on: treadmill (TREAD); plywood floor (PLY); and Teflon floor (TEF). Acceptable forces, cardiopulmonary and calf muscle oxygenation and blood volume responses were collected simultaneously while 12 men (age 39 +/- 13 years; height 178 +/- 6 cm; and body mass 91.5 +/- 16 kg) pushed for 2 h on each surface at their psychophysical workload. Participants selected higher forces on the PLY, resulting in higher pulmonary oxygen uptake compared to that of TEF (by approximately 9%) and TREAD (by approximately 18%). Pushing on the TEF demonstrated 50-56% lower blood volume changes and 1.5-1.8 times more oxygenation-force ratio than that for other surfaces. It is concluded that, to avoid a potential slip, participants were conservative in selecting acceptable forces to push on the slippery TEF. Part of this compensatory strategy on the TEF resulted in less muscle activity and, therefore, less demand for oxygen delivery to the calf muscle than for other surfaces. The present findings of significant force- and physiological-related differences in treadmill vs. high inertia pushcart clearly demonstrate that pushing experiments are essential to evaluate functional abilities of the workers.

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

LESSONS-LEARNED AND SUCCESS STORIES FROM EPA'S REAL-TIME ENVIRONMENTAL MONITORING, DATA DELIVERY, AND PUBLIC OUTREACH PROGRAM

EPA Science Inventory

TTSD has completed a series of technology transfer and risk communication handbooks, case studies, and summary reports for community-based environmental monitoring projects under EPA's Real-Time Environmental Monitoring, Data Delivery, and Public Outreach Program. The Program tak...

Shortening Delivery Times of Intensity Modulated Proton Therapy by Reducing Proton Energy Layers During Treatment Plan Optimization

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

Water, Steven van de, E-mail: s.vandewater@erasmusmc.nl; Kooy, Hanne M.; Heijmen, Ben J.M.

2015-06-01

Purpose: To shorten delivery times of intensity modulated proton therapy by reducing the number of energy layers in the treatment plan. Methods and Materials: We have developed an energy layer reduction method, which was implemented into our in-house-developed multicriteria treatment planning system “Erasmus-iCycle.” The method consisted of 2 components: (1) minimizing the logarithm of the total spot weight per energy layer; and (2) iteratively excluding low-weighted energy layers. The method was benchmarked by comparing a robust “time-efficient plan” (with energy layer reduction) with a robust “standard clinical plan” (without energy layer reduction) for 5 oropharyngeal cases and 5 prostate cases.more » Both plans of each patient had equal robust plan quality, because the worst-case dose parameters of the standard clinical plan were used as dose constraints for the time-efficient plan. Worst-case robust optimization was performed, accounting for setup errors of 3 mm and range errors of 3% + 1 mm. We evaluated the number of energy layers and the expected delivery time per fraction, assuming 30 seconds per beam direction, 10 ms per spot, and 400 Giga-protons per minute. The energy switching time was varied from 0.1 to 5 seconds. Results: The number of energy layers was on average reduced by 45% (range, 30%-56%) for the oropharyngeal cases and by 28% (range, 25%-32%) for the prostate cases. When assuming 1, 2, or 5 seconds energy switching time, the average delivery time was shortened from 3.9 to 3.0 minutes (25%), 6.0 to 4.2 minutes (32%), or 12.3 to 7.7 minutes (38%) for the oropharyngeal cases, and from 3.4 to 2.9 minutes (16%), 5.2 to 4.2 minutes (20%), or 10.6 to 8.0 minutes (24%) for the prostate cases. Conclusions: Delivery times of intensity modulated proton therapy can be reduced substantially without compromising robust plan quality. Shorter delivery times are likely to reduce treatment uncertainties and costs.« less

[Study on the status of institutional delivery and its determinants in rural Guangxi autonomous region].

PubMed

Li, Jian; Chen, Li-Li; Chen, Shu-Zhen; Cen, Ming-Yang; Zhao, Nai-Qing; Qian, Xu

2008-03-01

To understand the situation of institutional delivery of rural pregnant women in Guangxi Autonomous Region in the period of 1998 - 2003 and to identify the determinants on institutional delivery utilization. Using Andersen's behavioral model as analytical framework and Guangxi databank of the 3rd National Health Service Survey as data source, we described the status of institutional delivery with the rural women having had live birth history in the period of 1998 - 2003 as subjects, while and the univariate analysis and multivariate logistic analysis were done to identify determinants of institutional delivery utilization. Among a total number of 407 women with live birth history, 39.80 percent of them delivered at the health-care facilities. The rate of institutional delivery increased annually in 1998 - 2003 (P< 0.0001). The proportion of delivery in township health centers increased and the proportion of home delivery decreased by year (P< 0.0001). Results from both univariate and multivariate analysis showed that parity, education background of women, type of drinking water, time needed to get to the nearest healthcare facilities by the most convenient traffic,frequency of prenatal checkup, together with whether or not being advocated on institutional delivery etc. were determinants of delivery utilization. The OR value were 1.749 for multipara, 1.995 for those going to the nearest healthcare facilities by the most convenient traffic in less than 10 minutes, 3.011 for those drinking tap water, 5.435 for those with the education of high school, 29.149 for those with over 5 times in terms of frequency of prenatal checkup and 37.822 for those being advocated on institutional delivery. Socio-economic situation, status of maternal health care and parity made main contribution to institutional delivery and skilled birth attendance for women in rural Guangxi.

Time to delivery: Transfers for threatened preterm labour and prelabour rupture of membranes in Western Australia.

PubMed

Hollingworth, Jade; Pietsch, Rachel; Epee-Bekima, Mathias; Nathan, Elizabeth

2018-02-01

To describe the outcomes of patients transferred to King Edward Memorial Hospital (KEMH) with signs of labour at preterm gestations. A retrospective observational study of the 69 cases transferred to KEMH during 2015. Patient transfers from all locations across Western Australia (WA) to the sole tertiary perinatal centre in Perth. Pregnant women within WA with threatened or actual preterm labour (PTL) or preterm prelabour rupture of membranes (PPROM) between 23 and 32 weeks gestation. The occurrence of delivery during the admission and time-to-delivery as well as length of admission and association between clinical factors and time-to-delivery. The percentage of the study population delivered during the admission following transfer was 72.5%. Eighty-six per cent of those who delivered did so within 72 hours of transfer. The median time from transfer to delivery was 1 day. Sixty-three per cent of those who did not deliver during the admission progressed to 36 weeks gestation. Patients transferred with PPROM were less likely to deliver during the admission compared to those with uterine activity (50% versus 19.6%, P = 0.007) and nulliparas were more likely to deliver (93.5% versus 55.3%, P < 0.001). The majority of women transferred with signs of PTL progress to delivery during the same admission with the highest risk of delivery being the first 72 hours following transfer. If the pregnancy is ongoing at 72 hours, there is a reasonable chance of progression to late preterm gestation supporting the return of woman to their place of origin for antenatal care following discharge. © 2017 National Rural Health Alliance Inc.

Optimizing Retransmission Threshold in Wireless Sensor Networks

PubMed Central

Bi, Ran; Li, Yingshu; Tan, Guozhen; Sun, Liang

2016-01-01

The retransmission threshold in wireless sensor networks is critical to the latency of data delivery in the networks. However, existing works on data transmission in sensor networks did not consider the optimization of the retransmission threshold, and they simply set the same retransmission threshold for all sensor nodes in advance. The method did not take link quality and delay requirement into account, which decreases the probability of a packet passing its delivery path within a given deadline. This paper investigates the problem of finding optimal retransmission thresholds for relay nodes along a delivery path in a sensor network. The object of optimizing retransmission thresholds is to maximize the summation of the probability of the packet being successfully delivered to the next relay node or destination node in time. A dynamic programming-based distributed algorithm for finding optimal retransmission thresholds for relay nodes along a delivery path in the sensor network is proposed. The time complexity is OnΔ·max1≤i≤n{ui}, where ui is the given upper bound of the retransmission threshold of sensor node i in a given delivery path, n is the length of the delivery path and Δ is the given upper bound of the transmission delay of the delivery path. If Δ is greater than the polynomial, to reduce the time complexity, a linear programming-based (1+pmin)-approximation algorithm is proposed. Furthermore, when the ranges of the upper and lower bounds of retransmission thresholds are big enough, a Lagrange multiplier-based distributed O(1)-approximation algorithm with time complexity O(1) is proposed. Experimental results show that the proposed algorithms have better performance. PMID:27171092

HIV viraemia and mother-to-child transmission risk after antiretroviral therapy initiation in pregnancy in Cape Town, South Africa.

PubMed

Myer, L; Phillips, T K; McIntyre, J A; Hsiao, N-Y; Petro, G; Zerbe, A; Ramjith, J; Bekker, L-G; Abrams, E J

2017-02-01

Maternal HIV viral load (VL) drives mother-to-child HIV transmission (MTCT) risk but there are few data from sub-Saharan Africa, where most MTCT occurs. We investigated VL changes during pregnancy and MTCT following antiretroviral therapy (ART) initiation in Cape Town, South Africa. We conducted a prospective study of HIV-infected women initiating ART within routine antenatal services in a primary care setting. VL measurements were taken before ART initiation and up to three more times within 7 days postpartum. Analyses examined VL changes over time, viral suppression (VS) at delivery, and early MTCT based on polymerase chain reaction (PCR) testing up to 8 weeks of age. A total of 620 ART-eligible HIV-infected pregnant women initiated ART, with 2425 VL measurements by delivery (median gestation at initiation, 20 weeks; median pre-ART VL, 4.0 log 10 HIV-1 RNA copies/mL; median time on ART before delivery, 118 days). At delivery, 91% and 73% of women had VL ≤ 1000 and ≤ 50 copies/mL, respectively. VS was strongly predicted by time on therapy and pre-ART VL. The risk of early MTCT was strongly associated with delivery VL, with risks of 0.25, 2.0 and 8.5% among women with VL < 50, 50-1000 and > 1000 copies/mL at delivery, respectively (P < 0.001). High rates of VS at delivery and low rates of MTCT can be achieved in a routine care setting in sub-Saharan Africa, indicating the effectiveness of currently recommended ART regimens. Women initiating ART late in pregnancy and with high VL appear substantially less likely to achieve VS and require targeted research and programmatic attention. © 2016 British HIV Association.

ACTIVE DELIVERY CABLE TUNED TO DEVICE DEPLOYMENT STATE: ENHANCED VISIBILITY OF NITINOL OCCLUDERS DURING PRE-CLINICAL INTERVENTIONAL MRI

PubMed Central

Bell, Jamie A.; Saikus, Christina E.; Ratnayaka, Kanishka; Barbash, Israel M.; Faranesh, Anthony Z.; Franson, Dominique N.; Sonmez, Merdim; Slack, Michael C.; Lederman, Robert J.; Kocaturk, Ozgur

2012-01-01

Purpose To develop an active delivery system that enhances visualization of nitinol cardiac occluder devices during deployment under real-time MRI. Materials and Methods We constructed an active delivery cable incorporating a loopless antenna and a custom titanium microscrew to secure the occluder devices. The delivery cable was tuned and matched to 50Ω at 64 MHz with the occluder device attached. We used real-time balanced SSFP in a wide-bore 1.5T scanner. Device-related images were reconstructed separately and combined with surface-coil images. The delivery cable was tested in vitro in a phantom and in vivo in swine using a variety of nitinol cardiac occluder devices. Results In vitro, the active delivery cable provided little signal when the occluder device was detached and maximal signal with the device attached. In vivo, signal from the active delivery cable enabled clear visualization of occluder device during positioning and deployment. Device release resulted in decreased signal from the active cable. Post-mortem examination confirmed proper device placement. Conclusions The active delivery cable enhanced the MRI depiction of nitinol cardiac occluder devices during positioning and deployment, both in conventional and novel applications. We expect enhanced visibility to contribute to effectiveness and safety of new and emerging MRI-guided treatments. PMID:22707441

Timing of probiotic milk consumption during pregnancy and effects on the incidence of preeclampsia and preterm delivery: a prospective observational cohort study in Norway

PubMed Central

Nordqvist, Mahsa; Jacobsson, Bo; Brantsæter, Anne-Lise; Myhre, Ronny; Nilsson, Staffan; Sengpiel, Verena

2018-01-01

Objectives To investigate whether the timing of probiotic milk intake before, during early or late pregnancy influences associations with preeclampsia and preterm delivery. Design Population based prospective cohort study. Setting Norway, between 1999 and 2008. Participants 70 149 singleton pregnancies resulting in live-born babies from the Norwegian Mother and Child Cohort Study (no chronic disease, answered questionnaires, no placenta previa/cerclage/serious malformation of fetus, first enrolment pregnancy). Only nulliparous women (n=37 050) were included in the preeclampsia analysis. Both iatrogenic and spontaneous preterm delivery (between gestational weeks 22+0 and 36+6) with spontaneous term controls (between gestational weeks 39+0 and 40+6) were included in the preterm delivery analysis resulting in 34 458 cases. Main outcome measures Adjusted OR for preeclampsia and preterm delivery according to consumption of probiotic milk at three different time periods (before pregnancy, during early and late pregnancy). Results Probiotic milk intake in late pregnancy (but not before or in early pregnancy) was significantly associated with lower preeclampsia risk (adjusted OR: 0.80 (95% CI 0.68 to 0.94) p-value: 0.007). Probiotic intake during early (but not before or during late pregnancy) was significantly associated with lower risk of preterm delivery (adjusted OR: 0.79 (0.64 to 0.97) p-value: 0.03). Conclusions In this observational study, we found an association between timing of probiotic milk consumption during pregnancy and the incidence of the adverse pregnancy outcomes preeclampsia and preterm delivery. If future randomised controlled trials could establish a causal association between probiotics consumption and reduced risk of preeclampsia and preterm delivery, recommending probiotics would be a promising public health measure to reduce these adverse pregnancy outcomes. PMID:29362253

New labor management guidelines and changes in cesarean delivery patterns.

PubMed

Rosenbloom, Joshua I; Stout, Molly J; Tuuli, Methodius G; Woolfolk, Candice L; López, Julia D; Macones, George A; Cahill, Alison G

2017-12-01

In 2010 the Consortium on Safe Labor published labor curves. It was proposed that the rate of cesarean delivery could be lowered by avoiding the diagnosis of arrest of dilation before 6 cm. However, there is little information on the uptake of the guidelines and on changes in cesarean delivery rates that may have occurred. The objective of the study was to test the following hypotheses: (1) among patients laboring at term, rates of arrest of dilation disorders have decreased, leading to a decrease in the rate of cesarean delivery; (2) in the second stage, pushing duration prior to diagnosis of arrest of descent has increased, also leading to a reduction in the rate of cesarean delivery for this indication. As a secondary aim, we investigated changes in maternal and neonatal morbidity. This was a secondary analysis of a prospective cohort study of all patients presenting at ≥37 weeks' gestation from 2010 through 2014 with a nonanomalous vertex singleton and no prior history of cesarean delivery. Rates of cesarean delivery, arrest of dilation, and changes in rates of maternal and neonatal morbidity were calculated in crude and adjusted models. Cervical dilation at diagnosis of the arrest of dilation, time spent at the maximal dilation prior to diagnosis of arrest of dilation, and time in the second stage prior to the diagnosis of arrest of descent were compared over the study period. There were 7845 eligible patients. The cesarean delivery rate in 2010 was 15.8% and, in 2014, 17.7% (P trend = .51). In patients undergoing cesarean delivery for the arrest of dilation, the median cervical dilation at the time of cesarean delivery was at 5.5 cm in 2010 and 6.0 cm in 2014 (P trend = .94). In these patients, there was an increase in the time spent at last dilation: 3.8 hours in 2010 to 5.2 hours in 2014 (P trend = .02). There was no change in the frequency of patients diagnosed with the arrest of dilation at <6 cm: 51.4% in 2010 and 48.6% in 2014 (P trend = .56). However, in these patients, the median time spent at the last cervical dilation was 4.0 hours in 2010 and 6.7 hours in 2014 (P trend = .046). There were 206 cesarean deliveries for the arrest of descent. The median pushing time in these patients increased in multiparous patients from 1.1 hours in 2010 to 3.4 hours in 2014 (P trend = .009); in nulliparous patients these times were 2.7 hours in 2010 and 3.8 hours in 2014 (P trend = .09). There was a significant trend toward increasing adverse neonatal and maternal outcomes (P < .001 for each). The adjusted odds ratio for adverse maternal outcome for 2014 compared with 2010 was 1.66 (95% confidence interval, 1.27-2.17); however, considering only transfusion, hemorrhage, or infection, there was no difference (P trend = .96). The adjusted odds ratio of adverse neonatal outcome in 2014 compared with 2010 was 1.80 (95% confidence interval, 1.36-2.36). Despite significant changes in labor management that have occurred over the initial years since publication of the new labor curves and associated guidelines, the primary cesarean delivery rate was not reduced and there has been an increase in maternal and neonatal morbidity in our institution. A randomized controlled trial is needed. Copyright © 2017 Elsevier Inc. All rights reserved.

29 CFR 500.267 - Filing and service.

Code of Federal Regulations, 2011 CFR

2011-07-01

... SEASONAL AGRICULTURAL WORKER PROTECTION Administrative Proceedings Modification Or Vacation of Order of... copies. An original and two copies of all documents shall be filed. (c) Computation of time for delivery... by personal delivery or by mail. Service by mail is deemed effected at the time of mailing to the...

29 CFR 500.267 - Filing and service.

Code of Federal Regulations, 2010 CFR

2010-07-01

... SEASONAL AGRICULTURAL WORKER PROTECTION Administrative Proceedings Modification Or Vacation of Order of... copies. An original and two copies of all documents shall be filed. (c) Computation of time for delivery... by personal delivery or by mail. Service by mail is deemed effected at the time of mailing to the...

48 CFR 552.270-18 - Default in Delivery-Time Extensions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false Default in Delivery-Time Extensions. 552.270-18 Section 552.270-18 Federal Acquisition Regulations System GENERAL SERVICES... leases, in excess of the aggregate rent and estimated real estate tax and operating cost adjustments for...

48 CFR 552.270-18 - Default in Delivery-Time Extensions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false Default in Delivery-Time Extensions. 552.270-18 Section 552.270-18 Federal Acquisition Regulations System GENERAL SERVICES... leases, in excess of the aggregate rent and estimated real estate tax and operating cost adjustments for...

48 CFR 552.270-18 - Default in Delivery-Time Extensions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Default in Delivery-Time Extensions. 552.270-18 Section 552.270-18 Federal Acquisition Regulations System GENERAL SERVICES... leases, in excess of the aggregate rent and estimated real estate tax and operating cost adjustments for...

48 CFR 552.270-18 - Default in Delivery-Time Extensions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false Default in Delivery-Time Extensions. 552.270-18 Section 552.270-18 Federal Acquisition Regulations System GENERAL SERVICES... leases, in excess of the aggregate rent and estimated real estate tax and operating cost adjustments for...

12 CFR 263.12 - Construction of time limits.

Code of Federal Regulations, 2011 CFR

2011-01-01

.... Express Mail delivery, or first class, registered, or certified mail, upon deposit in or delivery to an appropriate point of collection; (iii) In the case of transmission by electronic media, as specified by the... time limits are calculated as follows: (1) If service is made by first class, registered, or certified...

12 CFR 509.12 - Construction of time limits.

Code of Federal Regulations, 2011 CFR

2011-01-01

... delivery, or first class, registered, or certified mail, upon deposit in or delivery to an appropriate point of collection; or (iii) In the case of transmission by electronic media, as specified by the... applicable time limits are calculated as follows: (1) If service is made by first class, registered, or...

Case-Based Instruction in Different Delivery Contexts: The Impact of Time in Cases

ERIC Educational Resources Information Center

Koury, Kevin; Hollingsead, Candice; Fitzgerald, Gail; Miller, Kevin; Mitchem, Katherine; Tsai, Hui-Hsien; Zha, Shenghua

2009-01-01

The focus of this article is a mixed methods naturalistic research project investigating the relationship between learners' time working within multimedia cases and learners' outcomes. Research was conducted across multiple delivery contexts in four universities. Participants were undergraduate and graduate teacher education students completing…

76 FR 52561 - Timely Mailing Treated as Timely Filing

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-23

... to the only ways to establish prima facie evidence of delivery of documents that have a filing... (PDS) designated under criteria established by the IRS, will constitute prima facie evidence of... taxpayers to be able to establish the postmark date and prima facie evidence of delivery when using...

48 CFR 552.270-18 - Default in Delivery-Time Extensions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Default in Delivery-Time Extensions. 552.270-18 Section 552.270-18 Federal Acquisition Regulations System GENERAL SERVICES... leases, in excess of the aggregate rent and estimated real estate tax and operating cost adjustments for...

A 5-mm piezo-scanning fiber device for high speed ultrafast laser microsurgery

PubMed Central

Ferhanoglu, Onur; Yildirim, Murat; Subramanian, Kaushik; Ben-Yakar, Adela

2014-01-01

Towards developing precise microsurgery tools for the clinic, we previously developed image-guided miniaturized devices using low repetition rate amplified ultrafast lasers for surgery. To improve the speed of tissue removal while reducing device diameter, here we present a new 5-mm diameter device that delivers high-repetition rate laser pulses for high speed ultrafast laser microsurgery. The device consists of an air-core photonic bandgap fiber (PBF) for the delivery of high energy pulses, a piezoelectric tube actuator for fiber scanning, and two aspheric lenses for focusing the light. Its inline optical architecture provides easy alignment and substantial size reduction to 5 mm diameter as compared to our previous MEMS-scanning devices while realizing improved intensity squared (two-photon) lateral and axial resolutions of 1.16 μm and 11.46 μm, respectively. Our study also sheds light on the maximum pulse energies that can be delivered through the air-core PBF and identifies cladding damage at the input facet of the fiber as the limiting factor. We have achieved a maximum energy delivery larger than 700 nJ at 92% coupling efficiency. An in depth analysis reveals how this value is greatly affected by possible slight misalignments of the beam during coupling and the measured small beam pointing fluctuations. In the absence of these imperfections, self-phase modulation becomes the limiting factor for the maximum energy delivery, setting the theoretical upper bound to near 2 μJ for a 1-m long, 7-μm, air-core PBF. Finally, the use of a 300 kHz repetition rate fiber laser enabled rapid ablation of 150 µm x 150 µm area within only 50 ms. Such ablation speeds can now allow the surgeons to translate the surgery device as fast as ~4 mm/s to continuously remove a thin layer of a 150 µm wide tissue. Thanks to a high optical transmission efficiency of the in-line optical architecture of the device and improved resolution, we could successfully perform ablation of scarred cheek pouch tissue, drilling through a thin slice. With further development, this device can serve as a precise and high speed ultrafast laser scalpel in the clinic. PMID:25071946

Improvements in Topical Ocular Drug Delivery Systems: Hydrogels and Contact Lenses.

PubMed

Ribeiro, Andreza Maria; Figueiras, Ana; Veiga, Francisco

2015-01-01

Conventional ophthalmic systems present very low corneal systemic bioavailability due to the nasolacrimal drainage and the difficulty to deliver the drug in the posterior segment of ocular tissue. For these reasons, recent advances have focused on the development of new ophthalmic drug delivery systems. This review provides an insight into the various constraints associated with ocular drug delivery, summarizes recent findings in soft contact lenses (SCL) and the applications of novel pharmaceutical systems for ocular drug delivery. Among the new therapeutic approaches in ophthalmology, SCL are novel continuous-delivery systems, providing high and sustained levels of drugs to the cornea. The tendency of research in ophthalmic drug delivery systems development are directed towards a combination of several technologies (bio-inspired and molecular imprinting techniques) and materials (cyclodextrins, surfactants, specific monomers). There is a tendency to develop systems which not only prolong the contact time of the vehicle at the ocular surface, but also at the same time slow down the clearance of the drug. Different materials can be applied during the development of contact lenses and can be combined with natural inspired strategies of drug immobilization and release, providing successful tools for ocular drug delivery systems.

Peri-tumoral leakage during intra-tumoral convection-enhanced delivery has implications for efficacy of peri-tumoral infusion before removal of tumor.

PubMed

Yang, Xiaoliang; Saito, Ryuta; Nakamura, Taigen; Zhang, Rong; Sonoda, Yukihiko; Kumabe, Toshihiro; Forsayeth, John; Bankiewicz, Krystof; Tominaga, Teiji

2016-01-01

In cases of malignant brain tumors, infiltrating tumor cells that exist at the tumor-surrounding brain tissue always escape from cytoreductive surgery and, protected by blood-brain barrier (BBB), survive the adjuvant chemoradiotherapy, eventually leading to tumor recurrence. Local interstitial delivery of chemotherapeutic agents is a promising strategy to target these cells. During our effort to develop effective drug delivery methods by intra-tumoral infusion of chemotherapeutic agents, we found consistent pattern of leakage from the tumor. Here we describe our findings and propose promising strategy to cover the brain tissue surrounding the tumor with therapeutic agents by means of convection-enhanced delivery. First, the intracranial tumor isograft model was used to define patterns of leakage from tumor mass after intra-tumoral infusion of the chemotherapeutic agents. Liposomal doxorubicin, although first distributed inside the tumor, distributed diffusely into the surrounding normal brain once the leakage happen. Trypan blue dye was used to evaluate the distribution pattern of peri-tumoral infusions. When infused intra- or peri-tumorally, infusates distributed robustly into the tumor border. Subsequently, volume of distributions with different infusion scheduling; including intra-tumoral infusion, peri-tumoral infusion after tumor resection, peri-tumoral infusion without tumor removal with or without systemic infusion of steroids, were compared with Evans-blue dye. Peri-tumoral infusion without tumor removal resulted in maximum volume of distribution. Prior use of steroids further increased the volume of distribution. Local interstitial drug delivery targeting tumor surrounding brain tissue before tumor removal should be more effective when targeting the invading cells.

Treatment of the Cornea Using Transcytotic Delivery into the Tear Film

DTIC Science & Technology

2015-12-01

early April 2013; however, we continue to produce additional material as required (Fig. 4). In milestone 3 we initiated in vivo evaluation of...SI, the minimum and maximum values are 12.4 and 34.4. 8 Aim 2) characterize Lacritin-ELP fusion proteins and evaluate as therapeutic agents...0.0001). Data were analyzed by a two-way ANOVA followed by Tukey’s multiple comparisons test (n=9). 10 Having evaluated the lacritin-ELP fusion in

The Toxicity of Inhaled Sulphur Mustard

DTIC Science & Technology

2012-10-01

Index − CO – Cardiac Output − CvO2 – Mixed Venous Oxygenation − CVP – Central Venous Pressure − DO2 – Oxygen Delivery − dpMax – Maximum...in central venous pressure following exposure to HD: HD controls () and HD + NAC (). Data are expressed as mean ± SEM. UK UNCLASSIFIED Page 64 of...Respiratory rate (RR) Heart rate (HR) Expired CO2 Pulse oximetry Mean arterial pressure Central venous pressure Blood Chemistry (arterial and

Spatial frequency performance limitations of radiation dose optimization and beam positioning

NASA Astrophysics Data System (ADS)

Stewart, James M. P.; Stapleton, Shawn; Chaudary, Naz; Lindsay, Patricia E.; Jaffray, David A.

2018-06-01

The flexibility and sophistication of modern radiotherapy treatment planning and delivery methods have advanced techniques to improve the therapeutic ratio. Contemporary dose optimization and calculation algorithms facilitate radiotherapy plans which closely conform the three-dimensional dose distribution to the target, with beam shaping devices and image guided field targeting ensuring the fidelity and accuracy of treatment delivery. Ultimately, dose distribution conformity is limited by the maximum deliverable dose gradient; shallow dose gradients challenge techniques to deliver a tumoricidal radiation dose while minimizing dose to surrounding tissue. In this work, this ‘dose delivery resolution’ observation is rigorously formalized for a general dose delivery model based on the superposition of dose kernel primitives. It is proven that the spatial resolution of a delivered dose is bounded by the spatial frequency content of the underlying dose kernel, which in turn defines a lower bound in the minimization of a dose optimization objective function. In addition, it is shown that this optimization is penalized by a dose deposition strategy which enforces a constant relative phase (or constant spacing) between individual radiation beams. These results are further refined to provide a direct, analytic method to estimate the dose distribution arising from the minimization of such an optimization function. The efficacy of the overall framework is demonstrated on an image guided small animal microirradiator for a set of two-dimensional hypoxia guided dose prescriptions.

Novel thermosensitive polymeric micelles for docetaxel delivery.

PubMed

Yang, Mi; Ding, Yitao; Zhang, Leyang; Qian, Xiaoping; Jiang, Xiqun; Liu, Baorui

2007-06-15

Targeted delivery of antitumor drugs triggered by hyperthermia has significant advantages in clinical applications, since it is easy to implement and side effects are reduced. To release drugs site-specifically upon local heating often requires the drugs to be loaded into a thermosensitive polymer matrix with a low critical solution temperature (LCST) between 37 and 42 degrees C. However, the LCSTs of most thermosensitive materials were below 37 degrees C, which limits their application in clinic because they would precipitate once injected into human body and lost thermal targeting function. Herein, we prepared a novel thermosensitive copolymer (poly(N-isopropylacrylamide-co-acrylamide)-b-poly (DL-lactide)) that exhibits no obvious physical change up to 41 degrees C when heated. Docetaxel loaded micelles made of such thermosensitive polymer were prepared by dialysis method and the maximum loading content was found to be up to 27%. The physical properties, such as structure, morphology, and size distribution of the micelles with and without docetaxel were investigated by NMR, X-ray diffraction, dynamic light scattering, atomic force microscopy, etc. The efficacy of this drug delivery system was also evaluated by examining the proliferation inhibiting activity against different cell lines in vitro. After hyperthermia, the cytotoxicity of docetaxel-loaded micelles increased prominently. Our results demonstrated that this copolymer could be an ideal candidate for thermal targeted antitumor drug delivery. (c) 2007 Wiley Periodicals, Inc.

Factors influencing choice of skilled birth attendance at ANC: evidence from the Kenya demographic health survey.

PubMed

Nyongesa, Caroline; Xu, Xiaoyue; Hall, John J; Macharia, William M; Yego, Faith; Hall, Brigid

2018-04-10

In Kenya, skilled attendance at delivery is well below the international target of 90% and the maternal mortality ratio is high at 362 (CI 254-471) per 100,000 live births despite various interventions. The preventative role of skilled attendance at delivery makes it a benchmark indicator for safe motherhood. Maternal health data from the Service Provision Assessment Survey, a subset of the 2010 Kenya Demographic Health Survey was analyzed. Logistic regression models were employed using likelihood ratio test to explore association between choice of skilled attendance and predictor variables. Overall, 94.8% of women are likely to seek skilled attendance at delivery. Cost, education level, number of antenatal visits and sex of provider were strongly associated with client's intention to deliver with a skilled birth attendant at delivery. Women who reported having enough money set aside for delivery were 4.34 (p < 0.002, 95% CI: 1.73; 10.87) times more likely to seek skilled attendance. Those with primary education and above were 6.6 times more likely to seek skilled attendance than those with no formal education (p < 0.001, 95% CI: 3.66; 11.95). Women with four or more antenatal visits were 5.95 (p < 0.018, 95% CI: 1.35; 26.18) times more likely to seek skilled attendance. Compared to men, female providers impacted more on the client's plan (OR = 2.02 (p < 0.014, 95% CI: 1.35; 3.53). Interventions aimed at improving skilled attendance at delivery should include promotion of formal education of women and financial preparation for delivery. Whenever circumstances permit, women should be allowed to choose gender of preferred professional attendant at delivery.

Pharmacokinetic characteristics of formulated alendronate transdermal delivery systems in rats and humans.

PubMed

Choi, Ahyoung; Gang, Hyesil; Whang, Jiae; Gwak, Hyesun

2010-05-01

The objective of this study was to examine the absorption of alendronate from formulated transdermal delivery systems in rats and humans. When alendronate was applied to rats by transdermal delivery systems (7.2 mg) and oral administration (30 mg/kg), a statistically significant difference was found in the amount remaining to be excreted at time t (Ae(t)) and the amount remaining to be excreted at time 0 (Ae(infinity)) (p < 0.01). The highest Ae(infinity) (1267.7+/-65.2 ng) was found in the formulation containing 6% caprylic acid in propylene glycol (PG), which was 5.4- and 2.0-times higher than the PG only formulation and oral administration, respectively. Compared to oral administration, significantly delayed half-life values were obtained from all the formulated transdermal delivery systems. There was a linear relationship (r(2) = 0.9854) between the drug loading dose and Ae(infinity). The Ae(infinity) values from the transdermal delivery system containing 6% caprylic acid (53.8 mg as alendronate) and an oral product (Fosamax), 70 mg as alendronate) in humans were 127.0 +/- 34.2 microg and 237.2 +/- 56.3 microg, respectively. The dose-adjusted relative Ae(infinity) ratio of the transdermal delivery system to oral product was calculated to be 69.7%. The long half-life of alendronate in the transdermal delivery system (50.6 +/- 6.4 h), compared to that of the oral product (3.5 +/- 1.1 h) could allow less-frequent dosing. In conclusion, this study showed that a transdermal delivery system containing 6% caprylic acid in PG could be a favorable alternative for alendronate administration.

Maternal and neonatal outcomes after implementation of a hospital policy to limit low-risk planned caesarean deliveries before 39 weeks of gestation: an interrupted time-series analysis.

PubMed

Hutcheon, J A; Strumpf, E C; Harper, S; Giesbrecht, E

2015-08-01

To evaluate the extent to which implementing a hospital policy to limit planned caesarean deliveries before 39 weeks of gestation improved neonatal health, maternal health, and healthcare costs. Retrospective cohort study. British Columbia Women's Hospital, Vancouver, Canada, in the period 2005-2012. Women with a low-risk planned repeat caesarean delivery. An interrupted time series design was used to evaluate the policy to limit planned caesarean deliveries before 39 weeks of gestation, introduced on 1 April 2008. Composite adverse neonatal health outcome (respiratory morbidity, 5-minute Apgar score of <7, neonatal intensive care unit admission, mortality), postpartum haemorrhage, obstetrical wound infection, out-of-hour deliveries, length of stay, and healthcare costs. Between 2005 and 2008, 60% (1204/2021) of low-risk planned caesarean deliveries were performed before 39 weeks of gestation. After the introduction of the policy, the proportion of planned caesareans dropped by 20 percentage points (adjusted risk difference of 20 fewer cases per 100 deliveries; 95% CI -25.8, -14.3) to 41% (1033/2518). The policy had no detectable impact on adverse neonatal outcomes (2.2 excess cases per 100; 95% CI -0.4, 4.8), maternal complications, or healthcare costs, but increased the risk of out-of-hours delivery from 16.2 to 21.1% (adjusted risk difference 6.3 per 100; 95% CI 1.6, 10.9). We found little evidence that a hospital policy to limit planned caesareans before 39 weeks of gestation reduced adverse neonatal outcomes. Hospital administrators intending to introduce such policies should anticipate, and plan for, modest increases in out-of-hours and emergency-timing. © 2015 Royal College of Obstetricians and Gynaecologists.

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

Chen, Q; Read, P

Purpose: Multiple error pathways can lead to delivery errors during the treatment course that cannot be caught with pre-treatment QA. While in vivo solutions are being developed for linacs, no such solution exists for tomotherapy. The purpose of this study is to develop a near real-time system for tomotherapy that can monitor the delivery and dose accumulation process during the treatment-delivery, which enable the user to assess the impact of delivery variations and/or errors and to interrupt the treatment if necessary. Methods: A program running on a tomotherapy planning station fetches the raw DAS data during treatment. Exit detector datamore » is extracted as well as output, gantry angle, and other machine parameters. For each sample, the MLC open-close state is determined. The delivered plan is compared with the original plan via a Monte Carlo dose engine which transports fluence deviations from a pre-treatment Monte Carlo run. A report containing the difference in fluence, dose and DVH statistics is created in html format. This process is repeated until the treatment is completed. Results: Since we only need to compute the dose for the difference in fluence for a few projections each time, dose with 2% statistical uncertainty can be computed in less than 1 second on a 4-core cpu. However, the current bottleneck in this near real-time system is the repeated fetching and processing the growing DAS data file throughout the delivery. The frame rate drops from 10Hz at the beginning of treatment to 5Hz after 3 minutes and to 2Hz after 10 minutes. Conclusion: A during-treatment delivery monitor system has been built to monitor tomotherapy treatments. The system improves patient safety by allowing operators to assess the delivery variations and errors during treatment delivery and adopt appropriate actions.« less

Experimental Shock Chemistry of Aqueous Amino Acid Solutions and the Cometary Delivery of Prebiotic Compounds

NASA Astrophysics Data System (ADS)

Blank, Jennifer G.; Miller, Gregory H.; Ahrens, Michael J.; Winans, Randall E.

2001-02-01

A series of shock experiments were conducted to assess the feasibility of the delivery of organic compounds to the Earth via cometary impacts. Aqueous solutions containing near-saturation levels of amino acids (lysine, norvaline, aminobutyric acid, proline, and phenylalanine) were sealed inside stainless steel capsules and shocked by ballistic impact with a steel projectile plate accelerated along a 12-m-long gun barrel to velocities of 0.5-1.9 km sec^-1. Pressure-temperature-time histories of the shocked fluids were calculated using 1D hydrodynamical simulations. Maximum conditions experienced by the solutions lasted 0.85-2.7 μs and ranged from 5.1-21 GPa and 412-870 K. Recovered sample capsules were milled open and liquid was extracted. Samples were analyzed using high performance liquid chromatography (HPLC) and mass spectrometry (MS). In all experiments, a large fraction of the amino acids survived. We observed differences in kinetic behavior and the degree of survivability among the amino acids. Aminobutyric acid appeared to be the least reactive, and phenylalanine appeared to be the most reactive of the amino acids. The impact process resulted in the formation of peptide bonds; new compounds included amino acid dimers and cyclic diketopiperazines. In our experiments, and in certain naturally occurring impacts, pressure has a greater influence than temperature in determining reaction pathways. Our results support the hypothesis that significant concentrations of organic material could survive a natural impact process.

Experimental shock chemistry of aqueous amino acid solutions and the cometary delivery of prebiotic compounds.

PubMed

Blank, J G; Miller, G H; Ahrens, M J; Winans, R E

2001-01-01

A series of shock experiments were conducted to assess the feasibility of the delivery of organic compounds to the Earth via cometary impacts. Aqueous solutions containing near-saturation levels of amino acids (lysine, norvaline, aminobutyric acid, proline, and phenylalanine) were sealed inside stainless steel capsules and shocked by ballistic impact with a steel projectile plate accelerated along a 12-m-long gun barrel to velocities of 0.5-1.9 km sec-1. Pressure-temperature-time histories of the shocked fluids were calculated using 1D hydrodynamical simulations. Maximum conditions experienced by the solutions lasted 0.85-2.7 microseconds and ranged from 5.1-21 GPa and 412-870 K. Recovered sample capsules were milled open and liquid was extracted. Samples were analyzed using high performance liquid chromatography (HPLC) and mass spectrometry (MS). In all experiments, a large fraction of the amino acids survived. We observed differences in kinetic behavior and the degree of survivability among the amino acids. Aminobutyric acid appeared to be the least reactive, and phenylalanine appeared to be the most reactive of the amino acids. The impact process resulted in the formation of peptide bonds; new compounds included amino acid dimers and cyclic diketopiperazines. In our experiments, and in certain naturally occurring impacts, pressure has a greater influence than temperature in determining reaction pathways. Our results support the hypothesis that significant concentrations of organic material could survive a natural impact process.

Clinical assessment of infant colour at delivery

PubMed Central

O'Donnell, Colm P F; Kamlin, C Omar F; Davis, Peter G; Carlin, John B; Morley, Colin J

2007-01-01

Objective Use of video recordings of newborn infants to determine: (1) if clinicians agreed whether infants were pink; and (2) the pulse oximeter oxygen saturation (Spo2) at which infants first looked pink. Methods Selected clips from video recordings of infants taken immediately after delivery were shown to medical and nursing staff. The infants received varying degrees of resuscitation (including none) and were monitored with pulse oximetry. The oximeter readings were obscured to observers but known to the investigators. A timer was visible and the sound was inaudible. The observers were asked to indicate whether each infant was pink at the beginning, became pink during the clip, or was never pink. If adjudged to turn pink during the clip, observers recorded the time this occurred and the corresponding Spo2 was determined. Results 27 clinicians assessed videos of 20 infants (mean (SD) gestation 31(4) weeks). One infant (5%) was perceived to be pink by all observers. The number of clinicians who thought each of the remaining 19 infants were never pink varied from 1 (4%) to 22 (81%). Observers determined the 10 infants with a maximum Spo2 ⩾95% never pink on 17% (46/270) of occasions. The Spo2 at which individual infants were perceived to turn pink varied from 10% to 100%. Conclusion Among clinicians observing the same videos there was disagreement about whether newborn infants looked pink with wide variation in the Spo2 when they were considered to become pink. PMID:17613535

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

NONE

Learnings Objectives: Although brachytherapy is the oldest form of radiation therapy, the rapid advancement of the methods of dose calculation, treatment planning and treatment delivery pushes us to keep updating our knowledge and experience to new procedures all the time. Our purpose is to present the newest applicators used in Accelerated Partial Breast Irradiation (APBI) and the techniques of using them for a maximum effective treatment. Our objective will be to get the user familiar with the Savi, Contura and ML Mammosite from the detailed description and measurements to cavity eval and choice or size, to acceptance tests and usemore » of each. At the end of the session the attendants will be able to assist at the scanning of the patient for the first treatment, decide on the proper localization and immobilization devices, import the scans in the treatment planning system, perform the structure segmentation, reconstruct the catheters and develop a treatment plan using inverse planning (IPSA) or volume optimization. The attendant should be able to evaluate the quality of a treatment plan according to the ABS protocols and B39 after this session. Our goal is that all the attendants to gain knowledge of all the quality assurance procedures required to be performed prior to a treatment, at the beginning of a treatment day, weekly, monthly and annualy on the remote afterloader, the treatment planning system and the secondary check system. We will provide tips for a consistent treatment delivery of the 10 fractions in a BID (twice daily) regimen.« less

Sternal Route More Effective than Tibial Route for Intraosseous Amiodarone Administration in a Swine Model of Ventricular Fibrillation.

PubMed

Burgert, James M; Martinez, Andre; O'Sullivan, Mara; Blouin, Dawn; Long, Audrey; Johnson, Arthur D

2018-01-01

The pharmacokinetics of IO administered lipid soluble amiodarone during ventricular fibrillation (VF) with ongoing CPR are unknown. This study measured mean plasma concentration over 5 minutes, maximum plasma concentration (Cmax), and time to maximum concentration (Tmax) of amiodarone administered by the sternal IO (SIO), tibial IO (TIO), and IV routes in a swine model of VF with ongoing CPR. Twenty-one Yorkshire-cross swine were randomly assigned to three groups: SIO, TIO, and IV. Ventricular fibrillation was induced under general anesthesia. After 4 minutes in VF, 300 mg amiodarone was administered as indicated by group assignment. Serial blood specimens collected at 30, 60, 90, 120, 150, 180, 240, and 300 seconds were analyzed using high performance liquid chromatography with tandem mass spectrometry. The mean plasma concentration of IV amiodarone over 5 minutes was significantly higher than the TIO group at 60 seconds (P = 0.02) and 90 seconds (P = 0.017) post-injection. No significant differences in Cmax between the groups were found (P <0.05). The Tmax of amiodarone was significantly shorter in the SIO (99 secs) and IV (86 secs) groups compared to the TIO group (215 secs); P = 0.002 and P = 0.002, respectively. The SIO and IV routes of amiodarone administration were comparable. The TIO group took nearly three times longer to reach Tmax than the SIO and IV groups, likely indicating depot of lipid-soluble amiodarone in adipose-rich tibial yellow bone marrow. The SIO route was more effective than the TIO route for amiodarone delivery in a swine model of VF with ongoing CPR. Further investigations are necessary to determine if the kinetic differences found between the SIO and TIO routes in this study affect survival of VF in humans.

Nicotine delivery, retention, and pharmacokinetics from various electronic cigarettes

PubMed Central

St. Helen, Gideon; Havel, Christopher; Dempsey, Delia; Jacob, Peyton; Benowitz, Neal L.

2015-01-01

Aims To measure the systemic retention of nicotine, propylene glycol (PG), and vegetable glycerin (VG) in electronic cigarette (e-cigarette) users, and assess the abuse liability of e-cigarettes by characterizing nicotine pharmacokinetics. Design E-cigarette users recruited over the Internet participated in a 1-day research ward study. Subjects took 15 puffs from their usual brand of e-cigarette. Exhaled breath was trapped in gas-washing bottles and blood was sampled before and several time after use. Setting San Francisco, California, USA. Participants Thirteen healthy, experienced adult e-cigarette users (6 females and 7 males). Measurements Plasma nicotine was analyzed by GC-MS/MS, and nicotine, VG, and PG in e-liquids and gas traps were analyzed by LC-MS/MS. Heart rate changes and subjective effects were assessed. Findings E-cigarettes delivered an average of 1.3 (0.9–1.8) mg (mean and 95% CI) of nicotine and 94% of the inhaled dose, 1.2 (0.8–1.7), was systemically retained. Average maximum plasma nicotine concentration (Cmax) was 8.4 (5.4–11.5) ng/mL and time of maximal concentration (Tmax) was 2 to 5 minutes; one participant had Tmax of 30 minutes. 89% and 92% of VG and PG, respectively, was systemically retained. Heart rate increased by an average of 8.0 bpm after 5 minutes. Withdrawal and urge to smoke decreased and the e-cigarettes were described as satisfying. Conclusions E-cigarettes can deliver levels of nicotine that are comparable to or higher than typical tobacco cigarettes, with similar systemic retention. Although the average maximum plasma nicotine concentration in experienced e-cigarettes users appears to be generally lower than what has been reported from tobacco cigarette use, the shape of the pharmacokinetic curve is similar, suggesting addictive potential. PMID:26430813

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.

SMS-Based Learning in Tertiary Education: Achievement and Attitudinal Outcomes

ERIC Educational Resources Information Center

Katz, Yaacov J.

2013-01-01

SMS delivery platforms are being increasingly used at the university level to enhance student achievement as well as traits and attitudes related to the learning process. SMS delivery provides access to learning materials without being limited by space or time and sophisticated technological advances in SMS delivery have led to enhanced learner…

36 CFR 1002.17 - Aircraft and air delivery.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 36 Parks, Forests, and Public Property 3 2012-07-01 2012-07-01 false Aircraft and air delivery... USE AND RECREATION § 1002.17 Aircraft and air delivery. (a) Delivering or retrieving a person or... devices designed to carry persons through the air in powerless flight is allowed at times and locations...

36 CFR 1002.17 - Aircraft and air delivery.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Aircraft and air delivery... USE AND RECREATION § 1002.17 Aircraft and air delivery. (a) Delivering or retrieving a person or... devices designed to carry persons through the air in powerless flight is allowed at times and locations...

Course Delivery Platform Changes and Instructional Delivery Methods: Student Attitudes and Perceptions

ERIC Educational Resources Information Center

Garner, William E.; Pack, Tresvil G.; Szirony, Gary M.; Beeson, Eric T.

2013-01-01

The purposes of this study were to examine students' perceptions and attitudes toward changes in Distance Education (DE) course management systems and to evaluate their instructional delivery preferences. Students (N = 145) enrolled in an online master's degree program on either a full- or part-time basis completed an online survey instrument…

Can we predict shoulder dystocia?

PubMed

Revicky, Vladimir; Mukhopadhyay, Sambit; Morris, Edward P; Nieto, Jose J

2012-02-01

To analyse the significance of risk factors and the possibility of prediction of shoulder dystocia. This was a retrospective cohort study. There were 9,767 vaginal deliveries at 37 and more weeks of gestation analysed during 2005-2007. Studied population included 234 deliveries complicated by shoulder dystocia. Shoulder dystocia was defined as a delivery that required additional obstetric manoeuvres to release the shoulders after gentle downward traction has failed. First, a univariate analysis was done to identify the factors that had a significant association with shoulder dystocia. Parity, age, gestation, induction of labour, epidural analgesia, birth weight, duration of second stage of labour and mode of delivery were studied factors. All factors were then combined in a multivariate logistic regression analysis. Adjusted odds ratios (Adj. OR) with 95% confidence intervals (CI) were calculated. The incidence of shoulder dystocia was 2.4% (234/9,767). Only mode of delivery and birth weight were independent risk factors for shoulder dystocia. Parity, age, gestation, induction of labour, epidural analgesia and duration of second stage of labour were not independent risk factors. Ventouse delivery increases the risk of shoulder dystocia almost 3 times, forceps delivery comparing to the ventouse delivery increases risk almost 3.4 times. Risk of shoulder dystocia is minimal with the birth weight of 3,000 g or less. It is difficult to foretell the exact birth weight and the mode of delivery, therefore occurrence of shoulder dystocia is highly unpredictable. Regular drills for shoulder dystocia and awareness of increased incidence with instrumental deliveries are important to reduce fetal and maternal morbidity and mortality.

Short and long term improvements in quality of chronic care delivery predict program sustainability.

PubMed

Cramm, Jane Murray; Nieboer, Anna Petra

2014-01-01

Empirical evidence on sustainability of programs that improve the quality of care delivery over time is lacking. Therefore, this study aims to identify the predictive role of short and long term improvements in quality of chronic care delivery on program sustainability. In this longitudinal study, professionals [2010 (T0): n=218, 55% response rate; 2011 (T1): n=300, 68% response rate; 2012 (T2): n=265, 63% response rate] from 22 Dutch disease-management programs completed surveys assessing quality of care and program sustainability. Our study findings indicated that quality of chronic care delivery improved significantly in the first 2 years after implementation of the disease-management programs. At T1, overall quality, self-management support, delivery system design, and integration of chronic care components, as well as health care delivery and clinical information systems and decision support, had improved. At T2, overall quality again improved significantly, as did community linkages, delivery system design, clinical information systems, decision support and integration of chronic care components, and self-management support. Multilevel regression analysis revealed that quality of chronic care delivery at T0 (p<0.001) and quality changes in the first (p<0.001) and second (p<0.01) years predicted program sustainability. In conclusion this study showed that disease-management programs based on the chronic care model improved the quality of chronic care delivery over time and that short and long term changes in the quality of chronic care delivery predicted the sustainability of the projects. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Regulation of Epithelial Cell Permeability by Nanostructured Thin Films

NASA Astrophysics Data System (ADS)

Stewart, Tarianna V.

Epithelia form barriers that regulate the movement of water, ions and molecules from one part of an organ to another. Facilitated transepithelial transport is important to enable drug delivery. Using human colon carcinoma (Caco-2) epithelial cells as a model, I found that contact with patterned nanostructured films (NSFs) enhanced the transepithelial transport of several different macromolecules without using chemical permeation agents. To determine the maximum paracellular permeability through tight junctions (TJs) I modified a calcium-"switch" model, as measured by the diffusion rate for all of the probes examined when media was changed from standard (20 mM) to low (10 microM) calcium. I then compared the permeability of Caco-2 cells in contact with NSFs to the maximum paracellular permeability of cells without NSFs at baseline. Caco-2 cells stimulated with NSFs showed an enhanced level of apical to basolateral transport for intact IgG compared to maximum paracellular permeability. However for the other probes examined, the paracellular permeability induced by NSFs was less than the maximum paracellular permeability of cells. These findings suggest that Caco-2 cells in contact with NSFs induce the specific, active transport of IgG from the apical to the basolateral cell surface of the epithelium. A series of experiments demonstrated the presence of so-called "neonatal" Fc receptors (FcRn) in Caco-2 cells and that these mediated the transcytosis of IgG across the cells. Moreover, contact with NSFs also enhanced paracellular transport, as determined by changes in TJ morphology and decreased transepithelial resistance (TER). To better understand the effects of NSFs on paracellular transport, we measured changes in matrix-metalloendoprotease (MMP) expression and activity was examined. MMP-2 and MMP-9 were upregulated by contact with NSFs. Roles for MMPs in regulating the effects of NSFs on epithelial cells are discussed. Thus, NSFs specifically enhance the transepithelial transport of agents in a substrate dependent manner utilizing both the transcellular and paracellular routes, suggesting that NSF-based devices are critical to developing a tunable drug delivery system.

Adhesion barriers at cesarean delivery: advertising compared with the evidence.

PubMed

Albright, Catherine M; Rouse, Dwight J

2011-07-01

Cesarean delivery, the most common surgery performed in the United States, is complicated by adhesion formation in 24-73% of cases. Because adhesions have potential sequelae, different synthetic adhesion barriers are currently heavily marketed as a means of reducing adhesion formation resultant from cesarean delivery. However, their use for this purpose has been studied in only two small, nonblinded and nonrandomized trials, both of which were underpowered and subject to bias. Neither demonstrated improvement in meaningful clinical outcomes. In the only cost-effectiveness analysis of adhesion barriers to date, the use of synthetic adhesion barriers was cost-effective only when the subsequent rate of small bowel obstruction was at least 2.4%, a rate far higher than that associated with cesarean delivery. In fact, intra-abdominal adhesions from prior cesarean delivery rarely cause maternal harm and have not been demonstrated to adversely affect perinatal outcome. Based on our review of the available literature, we think the use of adhesion barriers at the time of cesarean delivery would be ill-advised at the present time.

Continuing professional development and ICT: target practice.

PubMed

Eaton, K A; Reynolds, P A

2008-07-26

Ever-increasing needs and demands by dentists and all other members of the dental team for education and training at all levels - undergraduate, postgraduate and continuing - are straining the resources of existing providers of such education. At the same time, there are ever-increasing opportunities to develop online delivery and the use of a range of information and communication technology (ICT) systems and services further, in all aspects of dental education. This paper reviews recent developments that have led to an increased demand for dental postgraduate programmes and continuing professional development (CPD) courses in the United Kingdom and then discusses how ICT has and will impact on teaching practice. Examples include the use of teaching and learning resources in a virtual learning environment (VLE) and the increasing use of blended learning. The paper then explores the need for both teachers and students to adapt to the new environment to ensure they can benefit to the maximum and that teaching and learning practices are changed accordingly.

Tactile information transfer: A comparison of two stimulation sites

NASA Astrophysics Data System (ADS)

Summers, Ian R.; Whybrow, Jon J.; Gratton, Denise A.; Milnes, Peter; Brown, Brian H.; Stevens, John C.

2005-10-01

Two experiments on the discrimination of time-varying tactile stimuli were performed, with comparison of stimulus delivery to the distal pad of the right index finger and to the right wrist (palmar surface). Subjects were required to perceive differences in short sequences of computer-generated stimulus elements (experiment 1) or differences in short tactile stimuli derived from a speech signal (experiment 2). The pulse-train stimuli were distinguished by differences in frequency (i.e., pulse repetition rate) and amplitude, and by the presence/absence of gaps (~100-ms duration). Stimulation levels were 10 dB higher at the wrist than at the fingertip, to compensate for the lower vibration sensitivity at the wrist. Results indicate similar gap detection at wrist and fingertip and similar perception of frequency differences. However, perception of amplitude differences was found to be better at the wrist than at the fingertip. Maximum information transfer rates for the stimuli in experiment 1 were estimated at 7 bits s-1 at the wrist and 5 bits s-1 at the fingertip.

Physics and medicine: the Bevatron/Bevalac experience, 1979-1980

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

Lothrop, F.; Alonso, J.; Force, R.

1981-01-01

Heavy ion radiobiology has been integrated successfully into the research program at the Bevatron/Bevalac for the past several years. During the 1979 to 1980 year radiotherapy trials have been conducted side-by-side with the demanding program of heavy ion nuclear science research at this national facility. Careful attention is given to the scheduling of research on the SuperHILAC and Bevatron/Bevalac so that the nuclear science and biomedical programs at the Bevatron/Bevalac and the program at the SuperHILAC are served to maximum effect. Efforts to maximize the researchers' time have resulted in hardware, software, and operating improvements that offer a total machinemore » availability of about 90% and a user availability of about 80%. Fast beam switching and beam sharing permit virtually simultaneous use of the Bevatron/Bevalac by two or more users. Current beam delivery systems will be augmented in FY 1981 to provide two ion energies per Bevatron/Bevalac pulse.« less

Controlled release of astaxanthin from nanoporous silicified-phospholipids assembled boron nitride complex for cosmetic applications

NASA Astrophysics Data System (ADS)

Lee, Hye Sun; Sung, Dae Kyung; Kim, Sung Hyun; Choi, Won Il; Hwang, Ee Tag; Choi, Doo Jin; Chang, Jeong Ho

2017-12-01

Nanoporous silicified-phospholipids assembled boron nitride (nSPLs@BN) powder was prepared and demonstrated for use in controlled release of anti-oxidant astaxanthin (AX) as a cosmetic application. The nanoporous silicified phospholipids (nSPLs) were obtained by the silicification with tetraethyl orthosilicate (TEOS) of the hydrophilic region of phospholipid bilayers. This process involved the co-assembly of chemically active phospholipid bilayers within the porous silica matrix. In addition, nSPLs@BN was characterized using several analytical techniques and tested to assess their efficiency as drug delivery systems. We calculated the maximum release amounts as a function of time and various pH. The release rate of AX from the nSPLs@BN for the initial 24 h was 10.7 μmol/(h mg) at pH 7.4. Furthermore, we determined the antioxidant activity (KD) for the released AX with DPPH (1,1-diphenyl-2-picryl-hydrazyl) radical and the result was 34.6%.

A Green Media Access Method for IEEE 802.15.6 Wireless Body Area Network.

PubMed

Jacob, Anil K; Jacob, Lillykutty

2017-09-30

It is of utmost importance to conserve battery energy to the maximum possible extent in WBAN nodes while collecting and transferring medical data. The IEEE 802.15.6 WBAN standard does not specify any method to conserve energy. This paper focuses on a method to conserve energy in IEEE 802.15.6 WBAN nodes when using CSMA/CA, while simultaneously restricting data delivery delay to the required value as specified in medical applications. The technique is to allow the nodes to sleep all the times except for receiving beacons and for transmitting data frames whenever a data frame enters an empty buffer. The energy consumed by the nodes and the average latency of data frame for periodical arrival of data are found out analytically. The analytical results are validated and also the proposed method is compared with other energy conserving schemes, using Castalia simulation studies. The proposed method shows superior performance in both device lifetime and latency of emergency medical data.

Tumour-on-a-chip provides an optical window into nanoparticle tissue transport

NASA Astrophysics Data System (ADS)

Albanese, Alexandre; Lam, Alan K.; Sykes, Edward A.; Rocheleau, Jonathan V.; Chan, Warren C. W.

2013-10-01

Nanomaterials are used for numerous biomedical applications, but the selection of optimal properties for maximum delivery remains challenging. Thus, there is a significant interest in elucidating the nano-bio interactions underlying tissue accumulation. To date, researchers have relied on cell culture or animal models to study nano-bio interactions. However, cell cultures lack the complexity of biological tissues and animal models are prohibitively slow and expensive. Here we report a tumour-on-a-chip system where incorporation of tumour-like spheroids into a microfluidic channel permits real-time analysis of nanoparticle (NP) accumulation at physiological flow conditions. We show that penetration of NPs into the tissue is limited by their diameter and that retention can be improved by receptor targeting. NP transport is predominantly diffusion-limited with convection improving accumulation mostly at the tissue perimeter. A murine tumour model confirms these findings and demonstrates that the tumour-on-a-chip can be useful for screening optimal NP designs prior to in vivo studies.

Tactile information transfer: a comparison of two stimulation sites.

PubMed

Summers, lan R; Whybrow, Jon J; Gratton, Denise A; Milnes, Peter; Brown, Brian H; Stevens, John C

2005-10-01

Two experiments on the discrimination of time-varying tactile stimuli were performed, with comparison of stimulus delivery to the distal pad of the right index finger and to the right wrist (palmar surface). Subjects were required to perceive differences in short sequences of computer-generated stimulus elements (experiment 1) or differences in short tactile stimuli derived from a speech signal (experiment 2). The pulse-train stimuli were distinguished by differences in frequency (i.e., pulse repetition rate) and amplitude, and by the presence/absence of gaps (approximately 100-ms duration). Stimulation levels were 10 dB higher at the wrist than at the fingertip, to compensate for the lower vibration sensitivity at the wrist. Results indicate similar gap detection at wrist and fingertip and similar perception of frequency differences. However, perception of amplitude differences was found to be better at the wrist than at the fingertip. Maximum information transfer rates for the stimuli in experiment 1 were estimated at 7 bits s(-1) at the wrist and 5 bits s(-1) at the fingertip.

An investigation of wash-off controlling parameters at urban and commercial monitoring sites.

PubMed

Berretta, C; Gnecco, I; Lanza, L G; La Barbera, P

2007-01-01

The relationship between the parameters of the wash-off function and the controlling hydrologic variables are investigated in this paper, assuming that the pollutant generation process basically depends on the watershed rainfall-runoff response characteristics. Data collected during an intense monitoring program carried out by the Department of Environmental Engineering of the University of Genova (Italy) within a residential area, an auto dismantler facility, a tourism terminal and a urban waste truck depot are used to this aim. The observed runoff events are classified into different TSS mass delivery processes and the occurrence of the first flush phenomenon is also investigated. The correlation between the mathematical parameters describing the exponential process and the hydrological parameters of the corresponding rainfall-runoff event is analysed: runoff parameters and in particular the maximum flow discharge over the time of concentration of the drainage network are proposed as the controlling factor for the total mass of pollutant that is made available for wash-off during each runoff event.

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 chart review.« less

A software tool to automatically assure and report daily treatment deliveries by a cobalt‐60 radiation therapy device

PubMed Central

Wooten, H. Omar; Green, Olga; Li, Harold H.; Liu, Shi; Li, Xiaoling; Rodriguez, Vivian; Mutic, Sasa; Kashani, Rojano

2016-01-01

The aims of this study were to develop a method for automatic and immediate verification of treatment delivery after each treatment fraction in order to detect and correct errors, and to develop a comprehensive daily report which includes delivery verification results, daily image‐guided radiation therapy (IGRT) review, and information for weekly physics reviews. After systematically analyzing the requirements for treatment delivery verification and understanding the available information from a commercial MRI‐guided radiotherapy treatment machine, we designed a procedure to use 1) treatment plan files, 2) delivery log files, and 3) beam output information to verify the accuracy and completeness of each daily treatment delivery. The procedure verifies the correctness of delivered treatment plan parameters including beams, beam segments and, for each segment, the beam‐on time and MLC leaf positions. For each beam, composite primary fluence maps are calculated from the MLC leaf positions and segment beam‐on time. Error statistics are calculated on the fluence difference maps between the plan and the delivery. A daily treatment delivery report is designed to include all required information for IGRT and weekly physics reviews including the plan and treatment fraction information, daily beam output information, and the treatment delivery verification results. A computer program was developed to implement the proposed procedure of the automatic delivery verification and daily report generation for an MRI guided radiation therapy system. The program was clinically commissioned. Sensitivity was measured with simulated errors. The final version has been integrated into the commercial version of the treatment delivery system. The method automatically verifies the EBRT treatment deliveries and generates the daily treatment reports. Already in clinical use for over one year, it is useful to facilitate delivery error detection, and to expedite physician daily IGRT review and physicist weekly chart review. PACS number(s): 87.55.km PMID:27167269