bluuebunny/crossref_metadata_2025 huggingface dataset:
Poster ‐ 38: On the physical and dosimetric properties of 3D printed electron bolus fabricated using polylactic acid
Authors: Sasaki David , Jensen Martin , Rickey Daniel W , Dubey Arbind , Harris Chad , McCurdy Boyd
Published: August 2016

Purpose:

3D printing technology could simplify and improve electron bolus fabrication. The purpose of this study was to characterize the density, dimensional accuracy, uniformity, and attenuation of PLA boluses fabricated with a low‐cost 3D printer.

Methods:

Several solid square slabs were printed with specific requested dimensions and 100% infill using different fill patterns. These pieces were imaged using an x‐ray flat panel imager in order to check for uniformity of the prints.

Percentage depth doses (PDDs) were measured downstream of the slabs in solid water using a parallel plate chamber and compared to measurements in water in order to characterize attenuation.

The dimensions of the PLA slabs were measured using digital calipers. The slabs were also weighed to find their density.

Results:

The fill pattern used to create boluses can affect the attenuation of the bolus. Fill patterns should be chosen carefully and quality assurance should be done for each printed piece.

PLA causes the electron PDD to shift towards shallower depths, compared to water, by 1.7 mm for each centimeter of PLA.

Agreement with design dimensions was within 1 mm in the plane of the printer bed, and within 1/3 of a millimeter (roughly the thickness of a single layer), perpendicular to the printer bed. Average density was in the range 1.20 – 1.22.

Conclusions:

3D printing shows great promise for use in fabricating electron bolus. This work indicates that printed PLA can be a suitable material provided the increased attenuation is properly accounted for.
Poster ‐ 44: Development and implementation of a comprehensive end‐to‐end testing methodology for linac‐based frameless SRS QA using a modified commercial stereotactic anthropomorphic phantom
Authors: Liu Derek , Mutanga Theodore
Published: August 2016

Purpose:

An end‐to‐end testing methodology was designed to evaluate the overall SRS treatment fidelity, incorporating all steps in the linac‐based frameless radiosurgery treatment delivery process. The study details our commissioning experience of the Steev (CIRS, Norfolk, VA) stereotactic anthropomorphic head phantom including modification, test design, and baseline measurements.

Methods:

Repeated MR and CT scans were performed with interchanging inserts. MR‐CT fusion accuracy was evaluated and the insert spatial coincidence was verified on CT. Five non‐coplanar arcs delivered a prescription dose to a 15 mm spherical CTV with 2 mm PTV margin.

Following setup, CBCT‐based shifts were applied as per protocol. Sequential measurements were performed by interchanging inserts without disturbing the setup. Spatial and dosimetric accuracy was assessed by a combination of CBCT hidden target, radiochromic film, and ion chamber measurements. To facilitate film registration, the film insert was modified in‐house by etching marks.

Results:

MR fusion error and insert spatial coincidences were within 0.3 mm. Both CBCT and film measurements showed spatial displacements of 1.0 mm in similar directions. Both coronal and sagittal films reported 2.3 % higher target dose relative to the treatment plan. The corrected ion chamber measurement was similarly greater by 1.0 %. The 3 %/2 mm gamma pass rate was 99% for both films

Conclusions:

A comprehensive end‐to‐end testing methodology was implemented for our SRS QA program. The Steev phantom enabled realistic evaluation of the entire treatment process. Overall spatial and dosimetric accuracy of the delivery were 1 mm and 3 % respectively.
Poster ‐ 45: The effect of plan modulation on VMAT liver SBRT treatments: A motion interplay study
Authors: Hubley Emily , Hunter William , Sinha Richie , Pierce Greg
Published: August 2016

Purpose:

To investigate whether increasing the degree of MLC leaf modulation in VMAT liver SBRT treatment plans increases the dose differences due to the interplay effect.

Methods:

Two VMAT plans, delivering 54Gy in three fractions, with differing degrees of MLC aperture modulation were created for each of 10 patients. To simulate respiratory motion, an in‐house program was used to shift the positions of each active MLC leaf at every 0.6° of gantry rotation, according to the amplitude of a respiratory trace. To isolate the interplay effect from dose blurring, motion was simulated using four different starting points in the respiratory cycle. The same starting point was used for each of the three fractions, representing a worst case scenario. The four resultant dose distributions from each plan were subtracted from each other, and dose differences in the GTV were quantified using the standard deviation of the differential DVH.

Results:

Dose differences up to 1Gy were found in the GTV of the dose subtractions, indicating the presence of interplay effects. A Wilcoxon Signed Rank test indicates a significant (p<0.05) increase in the standard deviations of the low‐modulation plans to those with a higher degree of modulation. No planning constraints were exceeded with the introduction of respiratory motion.

Conclusions:

VMAT liver SBRT plans with a high degree of modulation exhibit an increased susceptibility to interplay effects. The dose differences due to interplay are not large enough to markedly decrease the plan quality.
Poster ‐ 51: A tumor motion‐compensating system with tracking and prediction – a proof‐of‐concept study
Authors: Guo Kaiming , Teo Peng (Troy) , Kawalec Philip , Pistorius Stephen
Published: August 2016

Purpose:

This work reports on the development of a mechanical slider system for the counter‐steering of tumor motion in adaptive Radiation Therapy (RT). The tumor motion was tracked using a weighted optical flow algorithm and its position is being predicted with a neural network (NN).

Methods:

The components of the proposed mechanical counter‐steering system includes: (1) an actuator which provides the tumor motion, (2) the motion detection using an optical flow algorithm, (3) motion prediction using a neural network, (4) a control module and (5) a mechanical slider to counter‐steer the anticipated motion of the tumor phantom. An asymmetrical cosine function and five patient traces (P1–P5) were used to evaluate the tracking of a 3D printed lung tumor. In the proposed mechanical counter‐steering system, both actuator (Zaber NA14D60) and slider (Zaber A‐BLQ0070‐E01) were programed to move independently with LabVIEW and their positions were recorded by 2 potentiometers (ETI LCP12S‐25). The accuracy of this counter‐steering system is given by the difference between the two potentiometers.

Results:

The inherent accuracy of the system, measured using the cosine function, is −0.15 ± 0.06 mm. While the errors when tracking and prediction were included, is (0.04 ± 0.71) mm.

Conclusion:

A prototype tumor motion counter‐steering system with tracking and prediction was implemented. The inherent errors are small in comparison to the tracking and prediction errors, which in turn are small in comparison to the magnitude of tumor motion. The results show that this system is suited for evaluating RT tracking and prediction.
Poster ‐ 52: Smoothing constraints in Modulated Photon Radiotherapy (XMRT) fluence map optimization
Authors: McGeachy Philip , Villarreal‐Barajas Jose Eduardo , Zinchenko Yuriy , Khan Rao
Published: August 2016

Purpose:

Modulated Photon Radiotherapy (XMRT), which simultaneously optimizes photon beamlet energy (6 and 18 MV) and fluence, has recently shown dosimetric improvement in comparison to conventional IMRT. That said, the degree of smoothness of resulting fluence maps (FMs) has yet to be investigated and could impact the deliverability of XMRT. This study looks at investigating FM smoothness and imposing smoothing constraint in the fluence map optimization.

Methods:

Smoothing constraints were modeled in the XMRT algorithm with the sum of positive gradient (SPG) technique. XMRT solutions, with and without SPG constraints, were generated for a clinical prostate scan using standard dosimetric prescriptions, constraints, and a seven coplanar beam arrangement. The smoothness, with and without SPG constraints, was assessed by looking at the absolute and relative maximum SPG scores for each fluence map. Dose volume histograms were utilized when evaluating impact on the dose distribution.

Results:

Imposing SPG constraints reduced the absolute and relative maximum SPG values by factors of up to 5 and 2, respectively, when compared with their non‐SPG constrained counterparts. This leads to a more seamless conversion of FMS to their respective MLC sequences. This improved smoothness resulted in an increase to organ at risk (OAR) dose, however the increase is not clinically significant.

Conclusions:

For a clinical prostate case, there was a noticeable improvement in the smoothness of the XMRT FMs when SPG constraints were applied with a minor increase in dose to OARs. This increase in OAR dose is not clinically meaningful.
Sci‐Fri AM: Quality, Safety, and Professional Issues 02: Recent work on TQC Suite and Data from a National survey on Community Uptake
Authors: Malkoske Kyle , Nielsen Michelle , Brown Erika , Diamond Kevin , Frenière Normand , Grant John , Pomerleau‐Dalcourt Natalie , Schella Jason , Schreiner L. John , Tantot Laurent , Barajas Eduardo Villareal , Sasaki David , Milette Marie‐Pierre , Bertrand Marie‐Joëlle , Bissonnette Jean‐Pierre
Published: August 2016

The Canadian Partnership for Quality Radiotherapy (CPQR) and the Canadian Organization of Medical Physicist's (COMP) Quality Assurance and Radiation Safety Advisory Committee (QARSAC) have worked together in the development of a suite of Technical Quality Control (TQC) Guidelines for radiation treatment equipment and technologies, that outline specific performance objectives and criteria that equipment should meet in order to assure an acceptable level of radiation treatment quality.

Early community engagement and uptake survey data showed 70% of Canadian centers are part of this process and that the data in the guideline documents reflect, and are influencing the way Canadian radiation treatment centres run their technical quality control programs.

As the TQC development framework matured as a cross‐country initiative, guidance documents have been developed in many clinical technologies. Recently, there have been new TQC documents initiated for Gamma Knife and Cyberknife technologies where the entire communities within Canada are involved in the review process.

At the same time, QARSAC reviewed the suite as a whole for the first time and it was found that some tests and tolerances overlapped across multiple documents as single tests could pertain to multiple quality control areas. The work to streamline the entire suite has allowed for improved usability of the suite while keeping the integrity of single quality control areas. The suite will be published by the JACMP, in the coming year.
Sci‐Fri AM: Quality, Safety, and Professional Issues 03: The Increasing Costs of Shielding Diagnostic CT Scanners in Ontario
Authors: Richer Jeff , Frimeth Jeff , Nesbitt James
Published: August 2016

Purpose:

In Ontario, shielding for all X‐ray machines, including CT scanners, must be evaluated according to Safety Code 20A (Health Canada, 1983) which is based on NCRP‐49 (NCRP, 1976).

NCRP‐147 (NCRP, 2004) is the international standard for shielding calculations of CT scanners and is also referenced in Safety Code 35 (Health Canada, 2008) which, was published to supersede SC20A. The goal of this work is to demonstrate the cost effectiveness of NCRP‐147 for CT scanner shielding.

Methods:

CT scanner shielding calculations are performed using SC20A and NCRP‐147:

A room located on the third floor with the nearest building 75m away

A room with high occupancy uncontrolled adjacent spaces

Two side by side rooms on the main floor

Results:

1. SC20A: The exterior windows required 0.1mm of Pb to protect the public who may occupy the building at 75m.

1. NCRP‐147: No additional shielding required.

2. SC20A: Two walls adjacent to high occupancy uncontrolled space required an additional 1.58mm Pb.

2. NCRP‐147: No additional shielding required.

3. SC20A: The entire floor and ceiling slabs in both rooms required an additional 0.79mm Pb. In addition, 0.79mm Pb was added to the walls from the ceiling to overlap the existing Pb shielding in the walls.

3. NCRP‐147: No additional shielding required.

Conclusion:

The application of NCRP Report No. 147 affords the required protection to staff and the public, in the true spirit of the ALARA principle, taking into account relevant social and economic factors.
Sci‐Fri PM: Radiation Therapy, Planning, Imaging, and Special Techniques ‐ 03: The Potential Benefit Of Esophageal Sparing During Palliative Radiotherapy For Lung Cancer
Authors: Granton Patrick V. , Palma David A. , Louie Alexander V.
Published: August 2016

Puropose:

Palliative radiotherapy is an effective technique to alleviate systems of disease burden in late‐stage lung cancer patients. Previous randomized controlled studies demonstrated a survival benefit in patients with good performance status at radiation doses of 35Gy10 or greater but with an increased incidence of esophagitis. The objective of this planning study was to assess the potential impact of esophageal‐sparing IMRT (ES‐IMRT) compared to the current standard of care using parallel‐opposed pair beams (POP).

Methods:

In this study, 15 patients with lung cancer treated to a dose of 30Gy in 10 fractions between August 2015 and January 2016 were identified. Radiation treatment plans were optimized using ES‐IMRT by limiting the max esophagus point dose to 24Gy. Using published Lyman‐Kutcher‐Burman normal tissue complication probabilities (LKB‐NTCP) models, both plans were evaluated for the likelihood of esophagitis (≥ grade 2) and pneumonitis (≥ grade 2).

Results:

Using ES‐IMRT, the median esophageal and lung mean doses reduced from 16 and 8Gy to 7 and 7Gy, respectively. Using the LKB models, the theoretical probability of symptomatic esophagitis and pneumonitis reduced from 13 to 1%, and from 5 to 3%, respectively. The median NTD mean for the GTV and PTV of the clinically approved POP plans compared to the ES‐IMRT plans were similar.

Conclusions:

Advanced radiotherapy techniques such as ES‐IMRT may have clinical utility in reducing treatment‐related toxicity in advanced lung cancer patients. Our data suggests that the rate of esophagitis can be reduced without compromising tumour control.
Sci‐Fri PM: Radiation Therapy, Planning, Imaging, and Special Techniques ‐ 11: Quantification of chest wall motion during deep inspiration breast hold treatments using cine EPID images and a physics based algorithm
Authors: Alpuche Aviles Jorge E. , Sasaki David , Rivest Ryan , VanBeek Timothy , Akra Mohamed
Published: August 2016

Purpose:

This work presents an algorithm used to quantify intra‐fraction motion for patients treated using deep inspiration breath hold (DIBH). The algorithm quantifies the position of the chest wall in breast tangent fields using electronic portal images.

Methods:

The algorithm assumes that image profiles, taken along a direction perpendicular to the medial border of the field, follow a monotonically and smooth decreasing function. This assumption is invalid in the presence of lung and can be used to calculate chest wall position. The algorithm was validated by determining the position of the chest wall for varying field edge positions in portal images of a thoracic phantom. The algorithm was used to quantify intra‐fraction motion in cine images for 7 patients treated with DIBH.

Results:

Phantom results show that changes in the distance between chest wall and field edge were accurate within 0.1 mm on average. For a fixed field edge, the algorithm calculates the position of the chest wall with a 0.2 mm standard deviation. Intra‐fraction motion for DIBH patients was within 1 mm 91.4% of the time and within 1.5 mm 97.9% of the time. The maximum intra‐fraction motion was 3.0 mm.

Conclusions:

A physics based algorithm was developed and can be used to quantify the position of chest wall irradiated in tangent portal images with an accuracy of 0.1 mm and precision of 0.6 mm. Intra‐fraction motion for patients treated with DIBH at our clinic is less than 3 mm.
Sci‐Sat AM: Radiation Dosimetry and Practical Therapy Solutions ‐ 05: Not all geometries are equivalent for magnetic field Fano cavity tests
Authors: Malkov Victor N. , Rogers David W.O.
Published: August 2016

The coupling of MRI and radiation treatment systems for the application of magnetic resonance guided radiation therapy necessitates a reliable magnetic field capable Monte Carlo (MC) code. In addition to the influence of the magnetic field on dose distributions, the question of proper calibration has arisen due to the several percent variation of ion chamber and solid state detector responses in magnetic fields when compared to the 0 T case (Reynolds et al., Med Phys, 2013). In the absence of a magnetic field, EGSnrc has been shown to pass the Fano cavity test (a rigorous benchmarking tool of MC codes) at the 0.1 % level (Kawrakow, Med.Phys, 2000), and similar results should be required of magnetic field capable MC algorithms. To properly test such developing MC codes, the Fano cavity theorem has been adapted to function in a magnetic field (Bouchard et al., PMB, 2015). In this work, the Fano cavity test is applied in a slab and ion‐chamber‐like geometries to test the transport options of an implemented magnetic field algorithm in EGSnrc. Results show that the deviation of the MC dose from the expected Fano cavity theory value is highly sensitive to the choice of geometry, and the ion chamber geometry appears to pass the test more easily than larger slab geometries. As magnetic field MC codes begin to be used for dose simulations and correction factor calculations, care must be taken to apply the most rigorous Fano test geometries to ensure reliability of such algorithms.
Sci‐Sat AM: Radiation Dosimetry and Practical Therapy Solutions ‐ 07: A mould room in a box – 3D scanning and printing technology in the radiotherapy clinic
Authors: Sasaki David , Rickey Daniel , Dubey Arbind , Alpuche Aviles Jorge E. , Johnson Kate , Sharma Ankur , Leylek Ahmet , Harris Chad , Boyer Todd , McCurdy Boyd , Butler Jim , Koul Rashmi
Published: August 2016

Purpose:

We describe the process by which our centre is currently implementing 3D printing and scanning technology for treatment accessory fabrication. This technology can increase efficiency and accuracy of accessory design, production and placement during daily use.

Methods:

A low‐cost 3D printer and 3D optical scanner have been purchased and are being commissioned for clinical use. Commissioning includes assessing: the accuracy of the 3D scanner through comparison with high resolution CT images; the dosimetric characteristics of polylactic acid (PLA) for electron beams; the clinical utility of the technology, and; methods for quality assurance.

Results:

The agreement between meshes generated using the 3D scanner and CT data was within 2 millimeters for an anthropomorphic head phantom. In terms of electron beam attenuation, 1 centimetre of printed PLA was found equivalent to 1.17 cm of water. In proof‐of‐concept tests, several types of treatment accessories have been prototyped to date that will benefit from this technology. These include electron and photon bolus for areas with complex surface contours including the ear for electron treatments, the extremities for photon treatments and lead shielding for orthovoltage treatments. Imaging with CT and x‐ray showed minimal defects, which will have no significant clinical impact. Geometric fidelity and fit to volunteers and patients was found to be excellent.

Conclusions:

3D Printing and scanning can increase efficiency in the clinic for treatments requiring custom accessories. Customized boluses and shielding had excellent fit and reduced uncertainty in positioning.
Sci‐Sat AM: Radiation Dosimetry and Practical Therapy Solutions ‐ 11: Commissioning of a system for the measurement of electron stopping powers
Authors: McEwen Malcolm , Roy Timothy , Tessier Frederic
Published: August 2016

Purpose:

To develop the techniques required to experimentally determine electron stopping powers for application in primary standards and dosimetry protocols.

Method and Materials:

A large‐volume HPGe detector system (>80% efficiency) was commissioned for the measurement of high energy (5–35 MeV) electron beams. As a proof of principle the system was used with a Y‐90/Sr‐90 radioactive source. Thin plates of absorbing material (< 0.1 gcm‐2) were then placed between the source and detector and the emerging electron spectrum was acquired. The full experimental geometry was modelled using the EGSnrc package to validate the detector design, optimize the experimental setup and compare measured and calculated spectra.

Results:

The biggest challenge using a beta source was to identify a robust spectral parameter to determine for each measurement. An end‐point‐fitting routine was used to determine the maximum energy, Emax, of the beta spectrum for each absorber thickness t. The parameter dEmax/dt is related to the electron stopping power and the same routine was applied to both measured and simulated spectra. Although the standard uncertainty in dEmax/dt was of the order of 5 %, by taking the ratio of measured and Monte Carlo values for dEmax/dt the uncertainty of the fitting routine was eliminated and the uncertainty was reduced to less than 2 %. The agreement between measurement and simulation was within this uncertainty estimate.

Conclusion:

The investigation confirmed the experimental approach and demonstrated that EGSnrc could accurately determine correction factors that will be required for the final measurement setup in a linac beam.
Magnetic Viscous Drag for Friction Labs
Authors: Gaffney Chris , Catching Adam
Published: August 2016

The typical friction lab performed in introductory mechanics courses is usually not the favorite of either the student or the instructor. The measurements are not all that easy to make, and reproducibility is usually a troublesome issue. This paper describes the augmentation of such a friction lab with a study of the viscous drag on a magnet sliding down a conducting ramp, e.g., an aluminum ramp (Fig. 1). The measurements are simple and quite reproducible, and it appears to readily catch the interest of students.
A debris-dammed lake threatens a flood
Authors: Service Robert F.
Published: August 2016

Engineers ponder fixes to Spirit Lake, bottled up 36 years ago by Mount St. Helens.
Tiger land
Authors: McLaughlin Kathleen
Published: August 2016

China's first national parks include a refuge for the world's largest cat.
Neuroimmunology
Authors: Mueller Kristen L. , Hines Pamela J. , Travis John
Published: August 2016

Immune cells on the brain
Wired
Authors: Underwood Emily
Published: August 2016

Beth Stevens and her network of collaborators are showing how immune cells sculpt connections in the brain
Inflammatory neuroprotection following traumatic brain injury
Authors: Russo Matthew V. , McGavern Dorian B.
Published: August 2016

Traumatic brain injury (TBI) elicits an inflammatory response in the central nervous system (CNS) that involves both resident and peripheral immune cells. Neuroinflammation can persist for years following a single TBI and may contribute to neurodegeneration. However, administration of anti-inflammatory drugs shortly after injury was not effective in the treatment of TBI patients. Some components of the neuroinflammatory response seem to play a beneficial role in the acute phase of TBI. Indeed, following CNS injury, early inflammation can set the stage for proper tissue regeneration and recovery, which can, perhaps, explain why general immunosuppression in TBI patients is disadvantageous. Here, we discuss some positive attributes of neuroinflammation and propose that inflammation be therapeutically guided in TBI patients rather than globally suppressed.
Comment on “A bacterium that degrades and assimilates poly(ethylene terephthalate)”
Authors: Yang Yu , Yang Jun , Jiang Lei
Published: August 2016

Yoshida
et al
. (Report, 11 March 2016, p. 1196) reported that the bacterium
Ideonella sakaiensis
201-F6 can degrade and assimilate poly(ethylene terephthalate) (PET). However, the authors exaggerated degradation efficiency using a low-crystallinity PET and presented no straightforward experiments to verify depolymerization and assimilation of PET. Thus, the authors’ conclusions are rather misleading.
Brazilian politics threaten environmental policies
Authors: Fearnside Philip M.
Published: August 2016

The country's environmental licensing system is threatened
Maternal immune activation: Implications for neuropsychiatric disorders
Authors: Estes Myka L. , McAllister A. Kimberley
Published: August 2016

Epidemiological evidence implicates maternal infection as a risk factor for autism spectrum disorder and schizophrenia. Animal models corroborate this link and demonstrate that maternal immune activation (MIA) alone is sufficient to impart lifelong neuropathology and altered behaviors in offspring. This Review describes common principles revealed by these models, highlighting recent findings that strengthen their relevance for schizophrenia and autism and are starting to reveal the molecular mechanisms underlying the effects of MIA on offspring. The role of MIA as a primer for a much wider range of psychiatric and neurologic disorders is also discussed. Finally, the need for more research in this nascent field and the implications for identifying and developing new treatments for individuals at heightened risk for neuroimmune disorders are considered.
Thermalization in small quantum systems
Authors: Polkovnikov Anatoli , Sels Dries
Published: August 2016

A small closed quantum many-body system shows evidence of thermalization
NS1 Protein Mutation I64T Affects Interferon Responses and Virulence of Circulating H3N2 Human Influenza A Viruses
Authors: DeDiego Marta L. , Nogales Aitor , Lambert-Emo Kris , Martinez-Sobrido Luis , Topham David J.
Published: August 2016

Influenza NS1 protein is the main viral protein counteracting host innate immune responses, allowing the virus to efficiently replicate in interferon (IFN)-competent systems. In this study, we analyzed NS1 protein variability within influenza A (IAV) H3N2 viruses infecting humans during the 2012-2013 season. We also evaluated the impact of the mutations on the ability of NS1 proteins to inhibit host innate immune responses and general gene expression. Surprisingly, a previously unidentified mutation in the double-stranded RNA (dsRNA)-binding domain (I64T) decreased NS1-mediated general inhibition of host protein synthesis by decreasing its interaction with cleavage and polyadenylation specificity factor 30 (CPSF30), leading to increased innate immune responses after viral infection. Notably, a recombinant A/Puerto Rico/8/34 H1N1 virus encoding the H3N2 NS1-T64 protein was highly attenuated in mice, most likely because of its ability to induce higher antiviral IFN responses at early times after infection and because this virus is highly sensitive to the IFN-induced antiviral state. Interestingly, using peripheral blood mononuclear cells (PBMCs) collected at the acute visit (2 to 3 days after infection), we show that the subject infected with the NS1-T64 attenuated virus has diminished responses to interferon and to interferon induction, suggesting why this subject could be infected with this highly IFN-sensitive virus. These data demonstrate the importance of influenza virus surveillance in identifying new mutations in the NS1 protein, affecting its ability to inhibit innate immune responses and, as a consequence, the pathogenicity of the virus.

IMPORTANCE
Influenza A and B viruses are one of the most common causes of respiratory infections in humans, causing 1 billion infections and between 300,000 and 500,000 deaths annually. Influenza virus surveillance to identify new mutations in the NS1 protein affecting innate immune responses and, as a consequence, the pathogenicity of the circulating viruses is highly relevant. Here, we analyzed amino acid variability in the NS1 proteins from human seasonal viruses and the effect of the mutations in innate immune responses and virus pathogenesis. A previously unidentified mutation in the dsRNA-binding domain decreased NS1-mediated general inhibition of host protein synthesis and the interaction of the protein with CPSF30. This mutation led to increased innate immune responses after viral infection, augmented IFN sensitivity, and virus attenuation in mice. Interestingly, using PBMCs, the subject infected with the virus encoding the attenuating mutation induced decreased antiviral responses, suggesting why this subject could be infected with this virus.
Equine Rhinitis A Virus Mutants with Altered Acid Resistance Unveil a Key Role of VP3 and Intrasubunit Interactions in the Control of the pH Stability of the Aphthovirus Capsid
Authors: Caridi Flavia , Cañas-Arranz Rodrigo , Vázquez-Calvo Angela , Sobrino Francisco , Martín-Acebes Miguel A.
Published: August 2016

Equine rhinitis A virus (ERAV) is a picornavirus associated with respiratory disease in horses and is genetically closely related to foot-and-mouth disease virus (FMDV), the prototype aphthovirus. ERAV has recently gained interest as an FMDV alternative for the study of aphthovirus biology, including cell entry and uncoating or antiviral testing. As described for FMDV, current data support that acidic pH inside cellular endosomes triggers ERAV uncoating. In order to provide further insights into aphthovirus uncoating mechanism, we have isolated a panel of ERAV mutants with altered acid sensitivity and that differed on their degree of sensitivity to the inhibition of endosome acidification. These results provide functional evidence of the involvement of acidic pH on ERAV uncoating within endosomes. Remarkably, all amino acid substitutions found in acid-labile or acid-resistant ERAVs were located in the capsid protein VP3, indicating that this protein plays a pivotal role for the control of pH stability of the ERAV capsid. Moreover, all amino acid substitutions mapped at the intraprotomer interface between VP3 and VP2 or between VP3 and the N terminus of VP1. These results expand our knowledge on the regions that regulate the acid stability of aphthovirus capsid and should be taken into account when using ERAV as a surrogate of FMDV.

IMPORTANCE
The viral capsid constitutes a sort of dynamic nanomachine that protects the viral genome against environmental assaults while accomplishing important functions such as receptor attachment for viral entry or genome release. We have explored the molecular determinants of aphthovirus capsid stability by isolating and characterizing a panel of equine rhinitis A virus mutants that differed on their acid sensitivity. All the mutations were located within a specific region of the capsid, the intraprotomer interface among capsid proteins, thus providing new insights into the regions that control the acid stability of aphthovirus capsid. These findings could positively contribute to the development of antiviral approaches targeting aphthovirus uncoating or the refinement of vaccine strategies based on capsid stabilization.
Molecular Basis for Strain Variation in the Saccharomyces cerevisiae Adhesin Flo11p
Authors: Barua Subit , Li Li , Lipke Peter N. , Dranginis Anne M.
Published: August 2016

As a nonmotile organism,
Saccharomyces cerevisiae
employs the cell surface flocculin Flo11/Muc1 as an important means of adapting to environmental change. However, there is a great deal of strain variation in the expression of Flo11-dependent phenotypes, including flocculation. In this study, we investigated the molecular basis of this strain-specific phenotypic variability. Our data indicate that strain-specific differences in the level of flocculation result from significant sequence differences in the
FLO11
alleles and do not depend on quantitative differences in
FLO11
expression or on surface hydrophobicity. We further have shown that beads coated with amino-terminal domain peptide bind preferentially to homologous cells. These data show that variability in the structure of the Flo11 adhesion domain may thus be an important determinant of membership in microbial communities and hence may drive selection and evolution.
PROLONGED INFUSIONS OF KETAMINE AND IMPACT ON INFECTIONS AND WASTE
Authors: Wong Joanne , Sutherland Adam
Published: August 2016

Aim

Ketamine is used for post-operative analgesia. There has been recent disruption in it's supply. It is usually prescribed by patient's weight (3 mg/kg in 50 ml 0.9% saline) at a rate of 1–5 ml/hr (1–5 microgram/kg/minute). To conserve ketamine supplies our policy was changed to a concentrated “standardised” concentration of ketamine (250 mg in 50 ml 0.9% sodium chloride) that could be run for a maximum of 72 hrs. There is evidence demonstrating no relationship between duration of infusion and microbiological contamination for 72 hrs.1 2 EPIC 3 guidelines recommend using infusion equipment for 72 hrs3.

We carried out a service evaluation to determine if prolonged infusions were with associated infection. We also evaluated the volume of ketamine that was discarded per patient.

Method

125 patients received ketamine (66 patients 24 hr infusions; 59 patients prolonged infusions.) 24 patients were randomly selected (12 per group). A retrospective chart review was undertaken. Data was collected on: duration of treatment (hrs); indicators of line infection (temperature, white cells, Visual Infusion Phlebitis Score (VIP)); number of syringes administered; volume administered (in ml).

Results

There were no clinical signs of infection in either cohort. No unexpected infections were reported. Concentrated ketamine ran for an average of 48 hrs per patient. 39.9% fewer syringes were used. Patients on 24 hr infusions received 55.8 ml ketamine and patients on long infusions received 51.5 ml ketamine. The amount of ketamine discarded was reduced by 65%.

Conclusion

Results should be interpreted with caution as patients had few co-morbidities, and received prophylactic antibiotics for surgery. These results suggest however that the risk of infusions running longer than 24 hrs is overstated. Our results raise important questions about the 24 hr expiry imposed on IV infusions. Further research on colonisation of ward-prepared infusions is needed.
CHANGING PRESCRIBING CULTURE – A FOCUS ON CODEINE POSTPARTUM
Authors: Al-Adhami Noor , Whitfield Karen , North Angela
Published: August 2016

Aim

To eliminate the prescribing of codeine and codeine combination products postpartum to improve safety in breast fed infants.

Concerns have been raised over the use of codeine and codeine combination products during breast feeding after the death of a neonate whose mother had been prescribed codeine postpartum. High concentrations of morphine were found in the infant's blood and this was attributed to the mother being a CYP2D6 ultrafast metaboliser.1

Methods

The evidence surrounding the safety of codeine and codeine combination products in children, during the postpartum period and specifically for breast fed infants was collated. The evidence was presented to key stakeholders including obstetricians, midwives, safety and quality representatives, nurse unit managers and acute pain team representatives. Postpartum analgesia was discussed and an agreed protocol developed. Training and education sessions were undertaken to obstetric medical and nursing staff.

Results

The evidence that was presented to key stakeholders included:

▸ Reports over the safety concerns surrounding the use of codeine and codeine combination products during breast feeding

▸ Guidelines and contraindications about the use of codeine in children that had been issued by international regulatory bodies (US Food and Drug Administration and European Medicines Agency).

▸ Recommendations from the Australian Medicines Handbook to avoid in breast feeding2

▸ Recommendations from Hale's Medications and Mothers Milk that reported limited data and had made a recent re-classification from L3 (limited data–probably compatible) to L4 (limited data–possibly hazardous).3

Before presenting the evidence to key stakeholders and undertaking training to nursing and medical staff, more than 90% of postpartum women were prescribed a codeine containing product as part of their ‘as required’ analgesic regimen.

Since the intervention, codeine combination products have now been almost completely eliminated on medication charts for postpartum women (less than 5%). Those that are prescribed are ceased once highlighted to medical staff. The obstetric pharmacist now presents a session on postpartum analgesia at every new resident medical officer orientation outlining suitable medications to prescribe. In addition all new pharmacists to the women's and new born's team receive training about postpartum analgesia.

Conclusion

This study highlights the impact that can be achieved when health care professionals work together to change the culture and prescribing habits in a hospital setting, to enhance patient safety. Evaluating the evidence and presenting to stakeholders as well as providing ongoing training and education to medical, nursing and pharmacy staff are all essential to a successful outcome.
INTER-INDIVIDUAL VARIATION IN THEOPHYLLINE CLEARANCE IN CHILDREN
Authors: Altamimi Mohammed , Choonara Imti , Sammons Helen
Published: August 2016

Background

Inter-individual variation in pharmacokinetics in children is an area where there has been little research. We wished to determine the extent of inter-individual variation in the clearance of theophylline in paediatric patients of different ages.

Methods

A systematic literature review was performed using the following databases; Embase (1974 to January 2013), Medline (1946 to January 2013), CINAHL (1937 to January 2013), International Pharmaceutical Abstracts (1970 to January 2013) and the Cochrane Library. From the papers, the range in plasma clearance and the coefficient of variation (CV) in plasma clearance were determined.

Results

A total of 56 articles reporting on 1,315 patients met our inclusion criteria. Twenty six studies gave individual data. The majority of the studies were in critically ill patients. Inter-individual variation was a major problem in all age groups. The CV was 9–93% in preterm neonates, 20–97% in term neonates, 18–52% in infants, 2–72% in children and 4.5–43% in adolescents. The mean clearance was higher in children (0.85 to 2 ml/min/kg) than in neonates (0.24 to 0.6 ml/min/kg).

Conclusions

Large inter-individual variation was seen, especially in critically ill patients. Inter-individual variation was higher in neonates than children and adolescents.
A STUDY OF THE EFFECT OF HYPOTONIC HYPER-HYDRATION FLUIDS ON SODIUM BALANCE IN PAEDIATRIC HAEMATOLOGY/ONCOLOGY PATIENTS RECEIVING CHEMOTHERAPY
Authors: Keane Sinead , Butler Eileen
Published: August 2016

Aims

To determine the effect, if any, that hyper-hydration with hypotonic fluids has on sodium balance in paediatric haematology/oncology patients receiving cytotoxic chemotherapy treatment for malignancies.

Methods

A literature review was carried out and a snapshot of current practice across paediatric haematology/oncology centres in the UK was obtained. A prospective study was carried out in a tertiary paediatric haematology/oncology centre. A total of 98 patient episodes involved hyper-hydration with isotonic 0.9% NaCl, almost isotonic 0.45% NaCl+2.5% glucose with added sodium bicarbonate or hypotonic 0.45% NaCl+2.5% glucose. Serum sodium was monitored before and during hyper-hydration. Results were analysed according to whether children experienced a drop in serum sodium.

Results

Patients who were hyper-hydrated with hypotonic 0.45% NaCl & 2.5% Glucose experienced the greatest mean drop in serum sodium. The mean drop in sodium was 2.11 mmol/L in the group receiving the hypotonic 0.45% NaCl & 2.5% Glucose compared to 0.47 mmol/L in the group who received isotonic 0.9% NaCl or 0.45% NaCl & 2.5% Glucose with added sodium bicarbonate. During the course of the study five patients who received 0.45% NaCl & 2.5% Glucose dropped their sodium to 130 mmol/L or less constituting hyponatraemia. No patient dropped their serum sodium to 130 mmol/L or less in the other two groups. During the course of the study no patient experienced clinical manifestations of hyponatraemia. No child became hypernatraemic.

Conclusions

In paediatric haematology/oncology patients receiving hyper-hydration with concurrent chemotherapy isotonic fluids are preferable.
RATES AND TYPES OF PRESCRIBING ERRORS AND RELATED INTERVENTIONS IN PAEDIATRIC ONCOLOGY
Authors: Fosbrook Claire
Published: August 2016

Aim

The aim of the pharmacy intervention audit was to prospectively record the number and type of interventions made to paediatric oncology chemotherapy prescriptions. This baseline data will be used in the future to assess the impact of electronic prescribing (EP) on prescribing error or intervention rates.

Independently from the EP project research, I interrogated the data to establish if there was a correlation between prescribing workload and rate of errors or interventions. I predicted that an ‘overworked’ prescriber would make more mistakes due to the volume of the workload and a less frequent prescriber would make more mistakes due to scarce use of these skills.

Intervention rates have been found to be as high as 66% for chemotherapy prescriptions, including interventions for missed information, wrong doses and protocol breach1. This intervention rate demonstrates the importance of pharmacy verification. Another source demonstrated that 80% of errors were due to poor prescription writing.2

Method

An audit tool was created to collect the data, included fields for date, prescriber type, number of drugs prescribed, number of interventions made and intervention type. Data was collected from 5 Jan 2015 to 12 Jun 15.

Results

The most common interventions required were addition of diluent volume, addition of start date and dose amendments to ensure doses could be accurately measured.

The staff grade doctor prescribed on average 75% of the prescriptions each week, with an intervention rate of 19%. The registrar was responsible for 23% each week and had an error rate pf 24%. Consultants were responsible for only 2% of the weekly prescription workload and had the lowest rate of interventions at 7%. There was no clear correlation between percentage of chemotherapy prescribed per week and rate of errors.

Conclusion

The most common types of errors expected from the background reading are demonstrated by this audit, as the three common interventions are related to poor prescribing. EP should eliminate all three of these interventions as all these are either mandatory fields for a prescription to be ordered or measurable dose rounding will be in inbuilt into each drug field, and therefore calculated automatically by our prescribing system.

There was no clear correlation between error rate and proportion of prescribing. Errors are therefore independent of prescribing workload. Alternative reasons for errors could include external factors such as environment or bad habits of the prescriber. I believe the low rate of errors from the consultants is due to the types of prescriptions they often prescribe. Which were more frequently for single agents such as intrathecals. This suggests further data interrogation could identify whether there is a relationship between prescription complexity (or length) and error rate.
ASSESSING PHARMACEUTICAL CARE NEEDS OF PAEDIATRIC IN-PATIENTS: A TEAM BASED APPROACH
Authors: Mott Adele , Kafka Susan , Sutherland Adam
Published: August 2016

Aims

To pilot a novel approach to providing pharmaceutical care to paediatric inpatients using structured referral and assessment tools. Using standardised referral criteria to ensure patients are assessed by appropriately skilled pharmacists.

Method

Three wards of varying acuity and specialism were selected in a tertiary children's hospital in England - General Paediatric Ward (GPW), High Dependency Unit (HDU) and Haematology/Oncology Ward (HOW). The project ran for three months.

Three levels of pharmacist were involved: Band 8 (“Level 3”), Paediatric Band 7 (“Level 2”) and rotational band 6/7 (“Level 1”). All patients were initially triaged by an appropriate pharmacist using criteria: Early Warning Scores (EWS), reason for admission, Level 1 Medicines Reconciliation. Patients were then graded according to level of acuity: Level 1: EWS 0–2 AND no significant medication history; Level 2: EWS 2–4 OR significant medication history; level 3: EWS >4.

After initial triage patients were handed over using SBAR1 in a structured group “huddle”, and acuity levels validated. Pharmaceutical care plans were formulated and patients allocated to appropriate pharmacists.

On the GPW patients were triaged by a level 3 pharmacist (“Refer Down”) for the first 2 weeks. On review of data generated and acuity levels triage was changed to be carried out by a level 1 pharmacist (“Refer Up.”) In the HDU and HOW the Refer Down system was used. All patients in the pilot were reassessed and acuity re-evaluated daily ensuring appropriate pharmacist review.

Data was collected on initial acuity level and any change in level following the huddle; (1) to identify those patients in need of a higher level of pharmaceutical input; (2) to identify the level of pharmacist most appropriate to a given clinical area.

Results

245 patients were assessed. 148 (83%) patients on GPW were triaged as level 1. Using a “refer down” model there was no change in patient acuity. Using “refer up” only 5 patients were reclassified to a higher level of care post-huddle.

18 (64%) patients in HOW were triaged as level 3. Eight patients were reduced to level 2 after the huddle. 53% of patients were classified as level 2 post-huddle. There were very few level 1 patients in HOW. PHDU demonstrated similar demographics, though with more level 1 patients.

Conclusion

This study demonstrates the potential benefits of a team based approach in optimising pharmaceutical care by directing patients to the most appropriate pharmacist. The huddle facilitates clinical supervision of patients and pharmacists. There may be benefits in efficiency using this system in a resource-constrained environment. This study does not present longitudinal changes in acuity. More research is needed.