bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sci‐Sat AM: Radiation Dosimetry and Practical Therapy Solutions ‐ 04: On 3D Fabrication of Phantoms and Experimental Verification of Patient Dose Computation Algorithms
Authors: Khan Rao , Zavan Rodolfo , McGeachy Philip , Madamesila Joseph , Villarreal‐Barajas Jose Eduardo 
Published: August 2016

Purpose:Transport based dose calculation algorithm Acuros XB (AXB) has been shown to accurately account for heterogeneities mostly through comparisons with Monte Carlo simulations. This study aims at providing additional experimental verification for AXB for flattened and unflattened clinical energies in low density phantoms of the same material.Materials and Methods:Polystyrene slabs were created using a bench‐top 3D printer. Six slabs were printed at varying densities from 0.23 g/cm3 to 0.68 g/cm3, corresponding to different density humanoid tissues. The slabs were used to form different single and multilayer geometries. Dose was calculated with AXB 11.0.31 for 6MV, 15MV flattened and 6FFF (flattening filter free) energies for field sizes of 2×2 cm2 and 5×5 cm2. The phantoms containing radiochromic EBT3 films were irradiated. Absolute dose profiles and 2D gamma analyses were performed for 96 dose planes.Results:For all single slab, multislab configurations and energies, absolute dose differences between the AXB calculation and film measurements remained <3% for both fields, with slightly poor disagreement in penumbra. The gamma index at 2% / 2mm averaged 98% in all combinations of fields, phantoms and photon energies.Conclusions:The transport based dose algorithm AXB is in good agreement with the experimental measurements for small field sizes using 6MV, 6FFF and 15MV beams adjacent to low density heterogeneous media. This work provides sufficient experimental ground to support the use of AXB for heterogeneous dose calculation purposes.
Sci‐Sat AM: Radiation Dosimetry and Practical Therapy Solutions ‐ 09: Stability of a water calorimetry system as a primary standard for absorbed dose to water
Authors: Cojocaru Claudiu , Mui Bryan , McEwen Malcolm , Ross Carl , Klassen Norman , Marchington David 
Published: August 2016

Purpose:To investigate the stability of a water calorimetry system as a primary standard for absorbed dose to water using measurements performed in cobalt‐60 and high‐energy linac photon beams over a span of more than a decade.Methods:Calorimetry measures adsorbed dose directly by recording the amount of heat created when ionizing radiation passes through matter. The radiation‐induced temperature rise was measured using two thermistors calibrated against the NRC temperature primary standard, using an AC bridge with lock‐in amplifier for precise measurement. The calorimeter system was operated under thermal equilibrium at 4 °C (to eliminate convection) with drifts in water temperature less than 0.1 mK/min. Seven water vessels of various designs were used to make repeated measurements over the course of 17 years.Results:The standard uncertainty achieved for a set of ten calorimeter measurements (4 Gy delivered) was generally well below 0.15 % while the variation between multiple sets for a given vessel was consistent with this value. The long‐term stability of the system combined with inter‐vessel variations indicated that there was good control of the radiochemistry (chemical heat defect).Conclusions:The measurements performed over a period of several years showed that the combined water calorimeters showed stability at +/− 0.25 % level. Thus, rather than relying on a particular vessel as an artifact one can realize the Gray through the more generalized method of combining a glass vessel, high‐purity water and thermistor probes. This provides increased robustness in the dissemination of absorbed dose to Canadian users.
Sci‐Sat AM: Radiation Dosimetry and Practical Therapy Solutions ‐ 12: Suitability of plan class specific reference fields for estimating dosimeter correction factors for small clinical CyberKnife fields
Authors: Vandervoort Eric , Christiansen Eric , Belec Jason , Muir Bryan 
Published: August 2016

Purpose:The purpose of this work is to investigate the utility of plan class specific reference (PCSR) fields for predicting dosimeter response within isocentric and non‐isocentric composite clinical fields using the smallest fields employed by the CyberKnife radiosurgery system.Methods:Monte Carlo dosimeter response correction factors (CFs) were calculated for a plastic scintillator and microchamber dosimeter in 21 clinical fields and 9 candidate plan‐class PCSR fields which employ the 5, 7.5 and 10 mm diameter collimators. Measurements were performed in 5 PCSR fields to confirm the predicted relative response of detectors in the same field.Results:Ratios of corrected measured dose in the PCSR fields agree to within 1% of unity. Calculated CFs for isocentric fields agree within 1.5% of those for PCSR fields. Large and variable microchamber CFs are required for non‐isocentric fields, with differences as high as 5% between different clinical fields in the same plan class and 4% within the same field depending on the point of measurement. Non‐isocentric PCSR fields constructed to have relatively homogenous dose over a region larger than the detector have very different ion chamber CFs from clinical fields. The plastic scintillator detector has much more consistent response within each plan class but still require 3–4% corrections in some fields.Conclusions:While the PCSR field concept is useful for small isocentric fields, this approach may not be appropriate for non‐isocentric clinical fields which exhibit large and variable ion chamber CFs which differ significantly from CFs for homogenous field PCSRs.
DDB1 Stimulates Viral Transcription of Hepatitis B Virus via HBx-Independent Mechanisms
Authors: Kim Woohyun , Lee Sooyoung , Son Yeongnam , Ko Chunkyu , Ryu Wang-Shick 
Published: August 2016

ABSTRACT
HBx, a small regulatory protein of hepatitis B virus (HBV), augments viral DNA replication by stimulating viral transcription. Among numerous reported HBx-binding proteins, DDB1 has drawn attention, because DDB1 acts as a substrate receptor of the Cul4-DDB1 ubiquitin E3 ligase. Previous work reported that the DDB1-HBx interaction is indispensable for HBx-stimulated viral DNA replication, suggesting that the Cul4-DDB1 ubiquitin E3 ligase might target cellular restriction factors for ubiquitination and proteasomal degradation. To gain further insight into the DDB1-HBx interaction, we generated HBx mutants deficient for DDB1 binding (i.e., R96A, L98A, and G99A) and examined whether they support HBx-stimulated viral DNA replication. In contrast to data from previous reports, our results showed that the HBx mutants deficient for DDB1 binding supported viral DNA replication to nearly wild-type levels, revealing that the DDB1-HBx interaction is largely dispensable for HBx-stimulated viral DNA replication. Instead, we found that DDB1 directly stimulates viral transcription regardless of HBx expression. Through an HBV infection study, importantly, we demonstrated that DDB1 stimulates viral transcription from covalently closed circular DNA, a physiological template for viral transcription. Overall, we concluded that DDB1 stimulates viral transcription via a mechanism that does not involve an interaction with HBx.

IMPORTANCE
DDB1 constitutes a cullin-based ubiquitin E3 ligase, where DDB1 serves as an adaptor linking the cullin scaffold to the substrate receptor. Previous findings that the DDB1-binding ability of HBx is essential for HBx-stimulated viral DNA replication led to the hypothesis that HBx could downregulate host restriction factors that limit HBV replication through the cullin ubiquitin E3 ligase that requires the DDB1-HBx interaction. Consistent with this hypothesis, recent work identified Smc5/6 as a host restriction factor that is regulated by the viral cullin ubiquitin E3 ligase. In contrast, here we found that the DDB1-HBx interaction is largely dispensable for HBx-stimulated viral DNA replication. Instead, our results clearly showed that DDB1, regardless of HBx expression, enhances viral transcription. Overall, besides its role in the viral cullin ubiquitin E3 ligase, DDB1 itself stimulates viral transcription via HBx-independent mechanisms.
Neglected but Important Role of Apolipoprotein E Exchange in Hepatitis C Virus Infection
Authors: Yang Zaili , Wang Xiaoning , Chi Xiumei , Zhao Fanfan , Guo Jinxu , Ma Pengjuan , Zhong Jin , Niu Junqi , Pan Xiaoyu , Long Gang 
Published: August 2016

ABSTRACT
Hepatitis C virus (HCV) is a major cause of chronic liver disease, infecting approximately 170 million people worldwide. HCV assembly is tightly associated with the lipoprotein pathway. Exchangeable apolipoprotein E (apoE) is incorporated on infectious HCV virions and is important for infectious HCV virion morphogenesis and entry. Moreover, the virion apoE level is positively correlated with its ability to escape E2 antibody neutralization. However, the role of apoE exchange in the HCV life cycle is unclear. In this study, the relationship between apoE expression and cell permissiveness to HCV infection was assessed by infecting apoE knockdown and derived apoE rescue cell lines with HCV. Exchange of apoE between lipoproteins and HCV lipoviral particles (LVPs) was evaluated by immunoprecipitation, infectivity testing, and viral genome quantification. Cell and heparin column binding assays were applied to determine the attachment efficiency of LVPs with different levels of incorporated apoE. The results showed that cell permissiveness for HCV infection was determined by exogenous apoE-associated lipoproteins. Furthermore, apoE exchange did occur between HCV LVPs and lipoproteins, which was important to maintain a high apoE level on LVPs. Lipid-free apoE was capable of enhancing HCV infectivity for apoE knockdown cells but not apoE rescue cells. A higher apoE level on LVPs conferred more efficient LVP attachment to both the cell surface and heparin beads. This study revealed that exogenous apoE-incorporating lipoproteins from uninfected hepatocytes safeguarded the apoE level of LVPs for more efficient attachment during HCV infection.

IMPORTANCE
In this study, a neglected but important role of apoE exchange in HCV LVP infectivity after virus assembly and release was identified. The data indicated that apoE expression level in uninfected cells is important for high permissiveness to HCV infection. Secreted apoE-associated lipoprotein specifically enhances infection of HCV LVPs. apoE exchange between HCV LVP and lipoproteins is important to maintain an adequate apoE level on LVPs for their efficient attachment to cell surface. These data defined for the first time an extracellular role of exchangeable apoE in HCV infection and suggested that exchangeable apolipoproteins reach a natural equilibrium between HCV LVPs and lipoprotein particles, which provides a new perspective to the understanding of the heterogeneity of HCV LVPs in composition.
Functional and Structural Characterization of P[19] Rotavirus VP8* Interaction with Histo-blood Group Antigens
Authors: Sun Xiaoman , Li Dandi , Peng Ruchao , Guo Nijun , Jin Miao , Zhou Yongkang , Xie Guangcheng , Pang Lili , Zhang Qing , Qi Jianxun , Duan Zhao-Jun 
Published: August 2016

ABSTRACT
Rotaviruses (RVs) of species A (RVA) are a major causative agent of acute gastroenteritis. Recently, histo-blood group antigens (HBGAs) have been reported to interact with human RVA VP8* proteins. Human P[19] is a rare P genotype of porcine origin that infects humans sporadically. The functional and structural characteristics of P[19] VP8* interaction with HBGAs are unknown. In this study, we expressed and purified the VP8* proteins of human and porcine P[19] RVs. In oligosaccharide and saliva binding assays, P[19] VP8* proteins showed obvious binding to A-, B-, and O-type saliva samples irrespective of the secretor status, implying broad binding patterns. However, they did not display specific binding to any of the oligosaccharides tested. In addition, we solved the structure of human P[19] VP8* at 2.4 Å, which revealed a typical galectin-like fold. The structural alignment demonstrated that P[19] VP8* was most similar to that of P[8], which was consistent with the phylogenetic analysis. Structure superimposition revealed the basis for the lack of binding to the oligosaccharides. Our study indicates that P[19] RVs may bind to other oligosaccharides or ligands and may have the potential to spread widely among humans. Thus, it is necessary to place the prevalence and evolution of P[19] RVs under surveillance.

IMPORTANCE
Human P[19] is a rare P genotype of porcine origin. Based on phylogenetic analysis of VP8* sequences, P[19] was classified in the P[II] genogroup, together with P[4], P[6], and P[8], which have been reported to interact with HBGAs in a genotype-dependent manner. In this study, we explored the functional and structural characteristics of P[19] VP8* interaction with HBGAs. P[19] VP8* showed binding to A-, B-, and O-type saliva samples, as well as saliva of nonsecretors. This implies that P[19] has the potential to spread among humans with a broad binding range. Careful attention should be paid to the evolution and prevalence of P[19] RVs. Furthermore, we solved the structure of P[19] VP8*. Structure superimposition indicated that P[19] may bind to other oligosaccharides or ligands using potential binding sites, suggesting that further investigation of the specific cell attachment factors is warranted.
Control of lithospheric inheritance on neotectonic activity in northwestern Canada?
Authors: Audet Pascal , Sole Christian , Schaeffer Andrew J. 
Published: August 2016

Abstract
Lithospheric inheritance is thought to affect the location and reactivation of tectonic structures through successive cycles of supercontinent formation and dispersal; however, its relation to neotectonic activity remains unclear. In northwestern Canada, abundant seismicity throughout the northern Canadian Cordillera (NCC) is geographically confined by several crustal-scale boundaries, yet its southern extent terminates abruptly along the inferred westward extension of a Late Cretaceous rifted margin boundary called the Liard transfer zone (LTZ). We use seismic data to show that the uppermost mantle beneath the Cordillera exhibits a sharp north-south contrast in fabric across the LTZ. South of the LTZ, fast axes of seismic wave propagation align closely with the lithospheric mantle fabric orientation of the adjacent Canadian shield. North of the LTZ, fast axes are reoriented subparallel to the motion of the Pacific plate and follow the strike of the large dextral strike-slip Tintina and Denali faults. We attribute changes in anisotropic delay times across the Tintina and Denali faults to localized shear within the lithosphere; this implies that the crust and lithospheric mantle remained mechanically coupled during shearing. We propose that the contrast in uppermost mantle structure across the LTZ reflects a change in the nature and origin of the lithospheric mantle from inherited rifted margin structures, which affects the stability of the lithosphere and limits the extent of seismic activity within the NCC. These results indicate that neotectonic activity in modern Cordilleras is controlled in part by inherited upper mantle structures.
TO INVESTIGATE THE EFFECT OF THE PASTEURISATION PROCESS ON TRACE ELEMENTS IN DONOR BREAST MILK
Authors: Taufek Nor Mohd , Cartwright David , Hewavitharana Amitha , Koorts Pieter , McConachy Helen , Shaw Nick , Whitfield Karen , Davies Mark 
Published: August 2016

AimTo investigate the effect of the pasteurisation process on trace elements in donor breast milk.MethodPremature infants often receive donor breast milk when the mother is unable to produce sufficient breast milk. It is widely accepted that donor milk has considerable advantages over formula milk.1 The Royal Brisbane and Women's Hospital (RBWH) has a milk bank that receives milk donated by women which undergoes a pasteurisation process.2 This study investigated the effect of pasteurisation on a range of trace elements in donor milk.A total of 14 participants who donated to the milk bank were recruited in this study. A 2 ml sample was collected pre- and post- pasteurisation, and frozen at −80 °C. Post-natal age of the milk was documented. Inductively-coupled plasma mass-spectrometry was used to analyse the following trace elements – zinc (Zn), copper (Cu), selenium (Se), manganese (Mn), iodine (I), iron (Fe), molybdenum (Mo) and bromine (Br). The study received ethical approval from RBWH and The University of Queensland Ethics Committee.ResultsNo significant difference was found between the levels of any of the trace elements tested pre- and post-pasteurisation. The following p-values were calculated – Zn (0.82), Cu (0.80), Se (0.97), Mn (0.63), I (0.99), Fe (0.05), Mo (0.41), Br (0.59). The following ranges in mcg/L of trace elements were calculated – Zn (365.4–5460.0), Cu (157.6–820.5), Se (10.6–23.7), Mn (0.55–3.24), I (66.4–215.3), Fe (101.5–473.1), Mo (0.20–5.45), Br (704.9–3379.0). Spearman's rank correlation analysis showed significant correlations between post-natal age of milk and trace elements – Zn (ρ=−0.578), Se (ρ=−0.627). Fe (ρ=−0.704), and Mo (ρ=−0.534). No significant correlation was found for Cu, Mn, I, and Br.ConclusionThis study found that the pasteurisation process had minimal effect on trace element levels in donor breast milk. However, it was noted that there was a correlation between post-natal age of donor milk and Zn, Se, Fe and Mo. Further work is needed to establish factors that may influence levels of trace elements in donor milk such as post-natal age.
THE APPROPRIATENESS OF USING AVERAGE DISPLACEMENT VALUES FOR PAEDIATRIC INTRAVENOUS DRUG ADMINISTRATIONS
Authors: Lo Alice , Christiansen Nanna , Bhatti Husnain 
Published: August 2016

AimTo determine the impact of displacement values on doses in paediatric patients when using parenteral. To assess the option of using average displacement values (DV) in the preparation of parenteral medicines.MethodOver 500 Medusa1 monographs were analysed and 42 medicines were identified with a displacement value not indicated as negligible. The following were calculated: the percentage difference in dose if the DV was not taken into account for each drug and brand, the range of percent differences where there was more than one brand for each strength and the percentage difference in dose incurred if an average DV was used.ResultsThe 42 drugs were separated into 3 groups. The first group of 27 drugs had DVs causing less than 5% dose variation for all brands. The second group of 7 drugs had DVs resulting in more than 5% dose variation. The third group of 8 drugs had wider variations i.e. including drugs where the different brands had DVs both below and above 5% (2 to 27.9%) in dose variations for varying brands of a drug and strength.A total of 64 preparations had less than 5% dose variation. For these the DVs could potentially be disregarded as it is unlikely to have a significant clinical effect. However there are other sources of errors when administering parenteral medications (e.g. dose rounding on prescribing, inaccuracy when preparing and drawing up the dose) and this may further contribute to cumulative dosing inaccuracies. An alternative option would be to provide an average DV for each drug and vial strength. Due to the use of an average DV under or over dosing can occur depending on the preparation. However if this method was used the dose difference is only 0.31% on average (0.47–0.98%), significantly less if the DV was ignored.For the second group of preparations with dose differences greater than 5% (5–18%), the DV should not be ignored as it can be clinically significant. However where there is more than one manufacturer available for a particular strength of drug the range in difference of the dose variation was small (0.7–4.1%). When an average displacement value was attributed this resulted in a maximum dose difference of 2.5% (0–2.5%). For the third group there are varying differences in the range of dose variation. Where the range is small and an average was assigned the average range in dose variation was 0.30% (0–4.6%). However there are preparations that the range was too wide for an average to be safely used (2.8–9.5%).ConclusionFor the majority of drugs an average DV can be used safely. Using average DVs would simplify the preparation process for nurses and reduce the risk of them inadvertently using the wrong displacement value.
DEVELOPMENT OF A ONCE DAILY GENTAMICIN REGIMEN FOR PAEDIATRIC SURGERY PATIENTS
Authors: Kasuji Sumayya , Gadaria Prady 
Published: August 2016

AimIntravenous gentamicin is given as a 5 day course to paediatric patients who have undergone abdominal surgery. There was an impression that the multiple daily dosing regimen in use at the time (2.5 mg/kg three times a day) did not provide therapeutic levels in this patient cohort therefore the aim was to develop a dosing regimen that did.MethodA retrospective audit of pre- and post-dose gentamicin levels in patients on a multiple daily dose regimen was undertaken. Data was gathered using a microbiology database and children aged between 1 month and 16 years who had gentamicin prophylaxis following abdominal surgery between January 2005 and January 2010 were included. Following on from the initial audit a once daily gentamicin dosing regimen was introduced for all patients who met the inclusion criteria: child aged over 1 month of age without ascites, cystic fibrosis, endocarditis, major burns or significant renal impairment and not pregnant. The once daily dose chosen was based on BNF-c guidance and an administration guideline was incorporated into a prescription chart. A survey of 7 hospitals and a literature review was conducted to determine when gentamicin levels were monitored. Once the regimen had been in place for 12 months a prospective audit of trough levels was undertaken.ResultsMultiple day dosing.336 children were reviewed, of these 35 had incomplete data and were excluded. Data was analysed from 301 children, 207 (68.7%) had a post dose below the recommended therapeutic range (5–10 mg/L) and the dose was increased by 10%. 132/207 of this subset had a second post dose measured and 99/132 (75%) were still below the therapeutic range. Overall, only 31.2% of children had gentamicin levels within the therapeutic range during the course of treatment.The Hartford nomogram has not been validated for use in children therefore it cannot it be applied to this patient cohort. The literature review and survey of practice revealed that with once daily dosing a peak gentamicin level does not need to be measured, as it is assumed that with a 7 mg/kg dose the pharmacodynamic goal of achieving a peak to minimum inhibitory concentration ratio greater than 104 will be achieved.1 2 Therefore, it is routine practice to only measure the trough level 1.Once daily dosingThirty patients were audited after the introduction of the once daily regimen and 100% of patients had a trough level of ≤1 mg/L.ConclusionA once daily gentamicin regimen of 7 mg/kg was found to achieve therapeutic levels in paediatric surgery patients who met the inclusion criteria when administered in accordance with the local prescription chart. A further audit is planned to determine if the new dosage regimen affects the clinical outcome.