bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the influence of pronounced diurnal temperature variations in nontemperate zones on the denitrification/nitrification rate using the COST Benchmark activated sludge model no. 1 simulation
Authors: Paul Parneet 
Published: November 2013

AbstractActivated sludge plants are usually designed using formulae based on fixed wastewater temperatures. In some nontemperate zones, these procedures may need altering, particularly for areas that experience large diurnal and seasonal temperature variation such as in desert or high‐altitude environments. This study investigates these temperature effects on the denitrification/nitrification rate by utilising the COST Benchmark activated sludge model no. 1 (ASM1) simulation model. The COST Benchmark was developed under the European Cooperation in Science and Technology programme Action 624 which specifically focused on the Optimal Management of Wastewater Systems. Various simulations and associated control strategies were carried out using gPROMS software package (Process Systems Enterprise Limited, London, UK) to ascertain the following: any likely nutrient removal implications; use of a nitrate and/or ammonia sensor coupled to a strategy to change the solids loading inventory to minimise falls in nitrification rate during night time hours; and changes to controller set point levels during the day and night to reflect diurnal load, flow and temperature variations using a temperature‐dependent control algorithm. It was found that inclusion of temperature dependency in simulation models may prove beneficial when designing plants located in these regions.
Velocity storage mechanism in zebrafish larvae
Authors: Chen Chien‐Cheng , Bockisch Christopher J. , Bertolini Giovanni , Olasagasti Itsaso , Neuhauss Stephan C. F. , Weber Konrad P. , Straumann Dominik , Ying‐Yu Huang Melody 
Published: November 2013

Key points
Five‐day‐old zebrafish larvae already exhibit a velocity storage mechanism (VSM).
The VSM in zebrafish larvae emerges earlier than a functional horizontal angular vestibular reflex.
The VSM may be critical to ocular motor control in larval zebrafish.
Abstract  The optokinetic reflex (OKR) and the angular vestibulo‐ocular reflex (aVOR) complement each other to stabilize images on the retina despite self‐ or world motion, a joint mechanism that is critical for effective vision. It is currently hypothesized that signals from both systems integrate, in a mathematical sense, in a network of neurons operating as a velocity storage mechanism (VSM). When exposed to a rotating visual surround, subjects display the OKR, slow following eye movements frequently interrupted by fast resetting eye movements. Subsequent to light‐off during optokinetic stimulation, eye movements do not stop abruptly, but decay slowly, a phenomenon referred to as the optokinetic after‐response (OKAR). The OKAR is most likely generated by the VSM. In this study, we observed the OKAR in developing larval zebrafish before the horizontal aVOR emerged. Our results suggest that the VSM develops prior to and without the need for a functional aVOR. It may be critical to ocular motor control in early development as it increases the efficiency of the OKR.
I‐125 ROPES eye plaque dosimetry: Validation of a commercial 3D ophthalmic brachytherapy treatment planning system and independent dose calculation software with GafChromic® EBT3 films
Authors: Poder Joel , Corde Stéphanie 
Published: November 2013

Purpose:The purpose of this study was to measure the dose distributions for different Radiation Oncology Physics and Engineering Services, Australia (ROPES) type eye plaques loaded with I‐125 (model 6711) seeds using GafChromic® EBT3 films, in order to verify the dose distributions in the Plaque Simulator™ (PS) ophthalmic 3D treatment planning system. The brachytherapy module of RADCALC® was used to independently check the dose distributions calculated by PS. Correction factors were derived from the measured data to be used in PS to account for the effect of the stainless steel ROPES plaque backing on the 3D dose distribution.Methods:Using GafChromic® EBT3 films inserted in a specially designed Solid Water™ eye ball phantom, dose distributions were measured three‐dimensionally both along and perpendicular to I‐125 (model 6711) loaded ROPES eye plaqueˈs central axis (CAX) with 2 mm depth increments. Each measurement was performed in full scatter conditions both with and without the stainless steel plaque backing attached to the eye plaque, to assess its effect on the dose distributions. Results were compared to the dose distributions calculated by Plaque Simulator™ and checked independently with RADCALC®.Results:The EBT3 film measurements without the stainless steel backing were found to agree with PS and RADCALC® to within 2% and 4%, respectively, on the plaque CAX. Also, RADCALC® was found to agree with PS to within 2%. The CAX depth doses measured using EBT3 film with the stainless steel backing were observed to result in a 4% decrease relative to when the backing was not present. Within experimental uncertainty, the 4% decrease was found to be constant with depth and independent of plaque size. Using a constant dose correction factor of T = 0.96 in PS, where the calculated dose for the full water scattering medium is reduced by 4% in every voxel in the dose grid, the effect of the plaque backing was accurately modeled in the planning system. Off‐axis profiles were also modeled in PS by taking into account the three‐dimensional model of the plaque backing.Conclusions:The doses calculated by PS and RADCALC® for uniformly loaded ROPES plaques in full and uniform scattering conditions were validated by the EBT3 film measurements. The stainless steel plaque backing was observed to decrease the measured dose by 4%. Through the introduction of a scalar correction factor (0.96) in PS, the dose homogeneity effect of the stainless steel plaque backing was found to agree with the measured EBT3 film measurements.
Motion‐map constrained image reconstruction (MCIR): Application to four‐dimensional cone‐beam computed tomography
Authors: Park Justin C. , Kim Jin Sung , Park Sung Ho , Liu Zhaowei , Song Bongyong , Song William Y. 
Published: November 2013

Purpose:Utilization of respiratory correlated four‐dimensional cone‐beam computed tomography (4DCBCT) has enabled verification of internal target motion and volume immediately prior to treatment. However, with current standard CBCT scan, 4DCBCT poses challenge for reconstruction due to the fact that multiple phase binning leads to insufficient number of projection data to reconstruct and thus cause streaking artifacts. The purpose of this study is to develop a novel 4DCBCT reconstruction algorithm framework called motion‐map constrained image reconstruction (MCIR), that allows reconstruction of high quality and high phase resolution 4DCBCT images with no more than the imaging dose as well as projections used in a standard free breathing 3DCBCT (FB‐3DCBCT) scan.Methods:The unknown 4DCBCT volume at each phase was mathematically modeled as a combination of FB‐3DCBCT and phase‐specific update vector which has an associated motion‐map matrix. The motion‐map matrix, which is the key innovation of the MCIR algorithm, was defined as the matrix that distinguishes voxels that are moving from stationary ones. This 4DCBCT model was then reconstructed with compressed sensing (CS) reconstruction framework such that the voxels with high motion would be aggressively updated by the phase‐wise sorted projections and the voxels with less motion would be minimally updated to preserve the FB‐3DCBCT. To evaluate the performance of our proposed MCIR algorithm, we evaluated both numerical phantoms and a lung cancer patient. The results were then compared with the (1) clinical FB‐3DCBCT reconstructed using the FDK, (2) 4DCBCT reconstructed using the FDK, and (3) 4DCBCT reconstructed using the well‐known prior image constrained compressed sensing (PICCS).Results:Examination of the MCIR algorithm showed that high phase‐resolved 4DCBCT with sets of up to 20 phases using a typical FB‐3DCBCT scan could be reconstructed without compromising the image quality. Moreover, in comparison with other published algorithms, the image quality of the MCIR algorithm is shown to be excellent.Conclusions:This work demonstrates the potential for providing high‐quality 4DCBCT during on‐line image‐guided radiation therapy (IGRT), without increasing the imaging dose. The results showed that (at least) 20 phase images could be reconstructed using the same projections data, used to reconstruct a single FB‐3DCBCT, without streak artifacts that are caused by insufficient projections.
Tomotherapy treatment plan quality assurance: The impact of applied criteria on passing rate in gamma index method
Authors: Bresciani Sara , Dia Amalia Di , Maggio Angelo , Cutaia Claudia , Miranti Anna , Infusino Erminia , Stasi Michele 
Published: November 2013

Purpose:Pretreatment patient plan verification with gamma index (GI) metric analysis is standard procedure for intensity modulated radiation therapy (IMRT) treatment. The aim of this paper is to evaluate the variability of the local and global gamma index obtained during standard pretreatment quality assurance (QA) measurements for plans performed with Tomotherapy unit. The QA measurements were performed with a 3D diode array, using variable passing criteria: 3%/3 mm, 2%/2 mm, 1%/1 mm, each with both local and global normalization.Methods:The authors analyzed the pretreatment QA results for 73 verifications; 37 were prostate cancer plans, 16 were head and neck plans, and 20 were other clinical sites. All plans were treated using the Tomotherapy Hi‐Art System. Pretreatment QA plans were performed with the commercially available 3D diode array ArcCHECK™. This device has 1386 diodes arranged in a helical geometry spaced 1 cm apart. The dose measurements were acquired on the ArcCHECK™ and then compared with the calculated dose using the standard gamma analysis method. The gamma passing rate (%GP), defined as the percentage of points satisfying the condition GI < 1, was calculated for different criteria (3%/3 mm, 2%/2 mm, 1%/1 mm) and for both global and local normalization. In the case of local normalization method, the authors set three dose difference threshold (DDT) values of 2, 3, and 5 cGy. Dose difference threshold is defined as the minimum absolute dose error considered in the analysis when using local normalization. Low‐dose thresholds (TH) of 5% and 10% were also applied and analyzed.Results:Performing a paired‐t‐test, the authors determined that the gamma passing rate is independent of the threshold values for all of the adopted criteria (5%TH vs 10%TH, p > 0.1). Our findings showed that mean %GPs for local (or global) normalization for the entire study group were 93% (98%), 84% (92%), and 66% (61%) for 3%/3 mm, 2%/2 mm, and 1%/1 mm criteria, respectively. DDT was equal to 2 cGy for the local normalization analysis cases. The authors observed great variability in the resulting %GP. With 3%/3 mm gamma criteria, the overall passing rate with local normalization was 4.6% less on the average than with global one, as expected. The wide difference between %GP calculated with global or local approach is also confirmed by an unpaired t‐test statistical analysis.Conclusions:The variability of %GP obtained confirmed the necessity to establish defined agreement criteria that could be universal and comparable between institutions. In particular, while the gamma passing rate does not depend on the choice of threshold, the choice of DDT strongly influences the gamma passing rate for local calculations. The difference between global and local %GP was statistically significant for prostate and other treatment sites when DDT was changed from 2 to 3 cGy.
A High-Content Phenotypic Screen Reveals the Disruptive Potency of Quinacrine and 3′,4′-Dichlorobenzamil on the Digestive Vacuole of Plasmodium falciparum
Authors: Lee Yan Quan , Goh Amanda S. P. , Ch'ng Jun Hong , Nosten François H. , Preiser Peter Rainer , Pervaiz Shazib , Yadav Sanjiv Kumar , Tan Kevin S. W. 
Published: November 2013

ABSTRACT

Plasmodium falciparum
is the etiological agent of malignant malaria and has been shown to exhibit features resembling programmed cell death. This is triggered upon treatment with low micromolar doses of chloroquine or other lysosomotrophic compounds and is associated with leakage of the digestive vacuole contents. In order to exploit this cell death pathway, we developed a high-content screening method to select compounds that can disrupt the parasite vacuole, as measured by the leakage of intravacuolar Ca
2+
. This assay uses the ImageStream 100, an imaging-capable flow cytometer, to assess the distribution of the fluorescent calcium probe Fluo-4. We obtained two hits from a small library of 25 test compounds, quinacrine and 3′,4′-dichlorobenzamil. The ability of these compounds to permeabilize the digestive vacuole in laboratory strains and clinical isolates was validated by confocal microscopy. The hits could induce programmed cell death features in both chloroquine-sensitive and -resistant laboratory strains. Quinacrine was effective at inhibiting field isolates in a 48-h reinvasion assay regardless of artemisinin clearance status. We therefore present as proof of concept a phenotypic screening method with the potential to provide mechanistic insights to the activity of antimalarial drugs.
In VitroPharmacodynamics of Human Simulated Exposures of Ceftaroline and Daptomycin against MRSA, hVISA, and VISA with and without Prior Vancomycin Exposure
Authors: Bhalodi Amira A. , Hagihara Mao , Nicolau David P. , Kuti Joseph L. 
Published: November 2013

ABSTRACTThe effects of prior vancomycin exposure on ceftaroline and daptomycin therapy against methicillin-resistantStaphylococcus aureus(MRSA) have not been widely studied. Humanized free-drug exposures of vancomycin at 1 g every 12 h (q12h), ceftaroline at 600 mg q12h, and daptomycin at 10 mg/kg of body weight q24h were simulated in a 96-hin vitropharmacodynamic model against three MRSA isolates, including one heteroresistant vancomycin-intermediateS. aureus(hVISA) isolate and one VISA isolate. A total of five regimens were tested: vancomycin, ceftaroline, and daptomycin alone for the entire 96 h, and then sequential therapy with vancomycin for 48 h followed by ceftaroline or daptomycin for 48 h. Microbiological responses were measured by the changes in log10CFU during 96 h from baseline. Control isolates grew to 9.16 ± 0.32, 9.13 ± 0.14, and 8.69 ± 0.28 log10CFU for MRSA, hVISA, and VISA, respectively. Vancomycin initially achieved ≥3 log10CFU reductions against the MRSA and hVISA isolates, followed by regrowth beginning at 48 h; minimal activity was observed against VISA. The change in 96-h log10CFU was largest for sequential therapy with vancomycin followed by ceftaroline (−5.22 ± 1.2,P= 0.010 versus ceftaroline) and for sequential therapy with vancomycin followed by ceftaroline (−3.60 ± 0.6,P= 0.037 versus daptomycin), compared with daptomycin (−2.24 ± 1.0), vancomycin (−1.40 ± 1.8), and sequential therapy with vancomycin followed by daptomycin (−1.32 ± 1.0,P> 0.5 for the last three regimens). Prior exposure of vancomycin at 1 g q12h reduced the initial microbiological response of daptomycin, particularly for hVISA and VISA isolates, but did not affect the response of ceftaroline. In the scenario of poor vancomycin response for high-inoculum MRSA infection, a ceftaroline-containing regimen may be preferred.
Urinary Concentrations and Antibacterial Activities of Nitroxoline at 250 Milligrams versus Trimethoprim at 200 Milligrams against Uropathogens in Healthy Volunteers
Authors: Wagenlehner Florian M. E. , Münch Fabian , Pilatz Adrian , Bärmann Birte , Weidner Wolfgang , Wagenlehner Christine M. , Straubinger Marion , Blenk Holger , Pfister Wolfgang , Kresken Michael , Naber Kurt G. 
Published: November 2013

ABSTRACT

Because of the increasing bacterial resistance of uropathogens against standard antibiotics, such as trimethoprim (TMP), older antimicrobial drugs, such as nitroxoline (NTX), should be reevaluated. This randomized crossover study investigated the urinary concentrations of parent drugs and their metabolites and their antibacterial activities (urinary inhibitory titers [UITs] and urinary bactericidal titers [UBTs]) against uropathogens at three different urinary pH values within 24 h in six healthy volunteers after a single oral dose of NTX at 250 mg versus TMP at 200 mg. In three additional volunteers, urinary bactericidal kinetics (UBK) were studied after oral administration of NTX at 250 mg three times a day. The mean urinary concentrations of NTX and NTX sulfate in 24 h were 0.012 to 0.507 mg/liter and 0.28 to 27.83 mg/liter, respectively. The mean urinary concentrations of TMP were 18.79 to 41.59 mg/liter. The antibacterial activity of NTX was higher in acidic urine than in alkaline urine, and that of TMP was higher in alkaline urine than in acidic urine. The UITs and UBTs of NTX were generally lower than those of TMP except for a TMP-resistant
Escherichia coli
strain, for which NTX showed higher UITs/UBTs than did TMP. UBK showed mainly bacteriostatic activity of NTX in urine. NTX exhibits mainly bacteriostatic activity and TMP also shows bactericidal activity in urine against susceptible strains. NTX is a more active antibacterial in acidic urine, and TMP is more active in alkaline urine. The cumulative effects of multiple doses or inhibition of bacterial adherence could not be evaluated. (This study has been registered at EudraCT under registration no. 2009-015631-32.)
Sequential Processing of Merozoite Surface Proteins during and after Erythrocyte Invasion by Plasmodium falciparum
Authors: Boyle Michelle J. , Langer Christine , Chan Jo-Anne , Hodder Anthony N. , Coppel Ross L. , Anders Robin F. , Beeson James G. 
Published: November 2013

ABSTRACT

Plasmodium falciparum
causes malaria disease during the asexual blood stages of infection when merozoites invade erythrocytes and replicate. Merozoite surface proteins (MSPs) are proposed to play a role in the initial binding of merozoites to erythrocytes, but precise roles remain undefined. Based on electron microscopy studies of invading
Plasmodium
merozoites, it is proposed that the majority of MSPs are cleaved and shed from the surface during invasion, perhaps to release receptor-ligand interactions. In this study, we demonstrate that there is not universal cleavage of MSPs during invasion. Instead, there is sequential and coordinated cleavage and shedding of proteins, indicating a diversity of roles for surface proteins during and after invasion. While MSP1 and peripheral surface proteins such as MSP3, MSP7, serine repeat antigen 4 (SERA4), and SERA5 are cleaved and shed at the tight junction between the invading merozoite and erythrocyte, the glycosylphosphatidylinositol (GPI)-anchored proteins MSP2 and MSP4 are carried into the erythrocyte without detectable processing. Following invasion, MSP2 rapidly degrades within 10 min, whereas MSP4 is maintained for hours. This suggests that while some proteins that are shed upon invasion may have roles in initial contact steps, others function during invasion and are then rapidly degraded, whereas others are internalized for roles during intraerythrocytic development. Interestingly, anti-MSP2 antibodies did not inhibit invasion and instead were carried into erythrocytes and maintained for approximately 20 h without inhibiting parasite development. These findings provide new insights into the mechanisms of invasion and knowledge to advance the development of new drugs and vaccines against malaria.
NLRP1 Is an Inflammasome Sensor for Toxoplasma gondii
Authors: Ewald Sarah E. , Chavarria-Smith Joseph , Boothroyd John C. 
Published: November 2013

ABSTRACT

The obligate intracellular parasite
Toxoplasma gondii
is able to infect nearly all nucleated cell types of warm-blooded animals. This is achieved through the injection of hundreds of parasite effectors into the host cell cytosol, allowing the parasite to establish a vacuolar niche for growth, replication, and persistence. Here we show that
Toxoplasma
infection actives an inflammasome response in mice and rats, an innate immune sensing system designed to survey the host cytosol for foreign components leading to inflammation and cell death. Oral infection with
Toxoplasma
triggers an inflammasome response that is protective to the host, limiting parasite load and dissemination.
Toxoplasma
infection is sufficient to generate an inflammasome response in germfree animals. Interleukin 1β (IL-1β) secretion by macrophage requires the effector caspases 1 and 11, the adapter ASC, and NLRP1, the sensor previously described to initiate the inflammasome response to
Bacillus anthracis
lethal factor. The allele of NLRP1b derived from 129 mice is sufficient to enhance the B6 bone marrow-derived macrophage (BMDM) inflammasome response to
Toxoplasma
independent of the lethal factor proteolysis site. Moreover, N-terminal processing of NLRP1b, the only mechanism of activation known to date, is not observed in response to
Toxoplasma
infection. Cumulatively, these data indicate that NLRP1 is an innate immune sensor for
Toxoplasma
infection, activated via a novel mechanism that corresponds to a host-protective innate immune response to the parasite.
What tools are available to identify patients with palliative care needs in primary care: a systematic literature review and survey of European practice
Authors: Maas Elke Arnoldina Theodora , Murray Scott A , Engels Yvonne , Campbell Christine 
Published: November 2013

BackgroundIt can be difficult to identify when a palliative care approach should be started both in malignant, and particularly, in non-malignant disease, ideally to run alongside disease-modifying care. A structured method or tool may be useful to help general practitioners (GPs) identify patients for early palliative care and trigger assessment and care planning.AimsTo document what tools for identification of patients with palliative care needs are available in the published literature and to ascertain how GPs in Europe currently identify patients for palliative care.MethodsA systematic literature search using PubMed and Embase, and a questionnaire survey among key informants in 14 European countries requesting data on methods used to identify patients with palliative care needs.ResultsThe literature search identified four tools. The questionnaire survey identified a further three in current use and found that in current practice identification is largely based on a GP's own clinical judgement and information received from the hospital: tools are rarely used.ConclusionsAlthough several identification tools have been developed, none of these have been validated or widely implemented in Europe. Further collaborative international development, implementation and evaluation of such tools are recommended.