Correlation of phantom-based and log file patient-specific QA with complexity scores for VMAT

The motivation for this study was to reduce physics workload relating to patient- specific quality assurance (QA). VMAT plan delivery accuracy was determined from analysis of pre- and on-treatment trajectory log files and phantom-based ionization chamber array measurements. The correlation in this combination of measurements for patient-specific QA was investigated. The relationship between delivery errors and plan complexity was investigated as a potential method to further reduce patient-specific QA workload. Thirty VMAT plans from three treatment sites - prostate only, prostate and pelvic node (PPN), and head and neck (H&N) - were retrospectively analyzed in this work. The 2D fluence delivery reconstructed from pretreatment and on-treatment trajectory log files was compared with the planned fluence using gamma analysis. Pretreatment dose delivery verification was also car- ried out using gamma analysis of ionization chamber array measurements compared with calculated doses. Pearson correlations were used to explore any relationship between trajectory log file (pretreatment and on-treatment) and ionization chamber array gamma results (pretreatment). Plan complexity was assessed using the MU/ arc and the modulation complexity score (MCS), with Pearson correlations used to examine any relationships between complexity metrics and plan delivery accu- racy. Trajectory log files were also used to further explore the accuracy of MLC and gantry positions. Pretreatment 1%/1 mm gamma passing rates for trajectory log file analysis were 99.1% (98.7%-99.2%), 99.3% (99.1%-99.5%), and 98.4% (97.3%-98.8%) (median (IQR)) for prostate, PPN, and H&N, respectively, and were significantly correlated to on-treatment trajectory log file gamma results (R = 0.989, p < 0.001). Pretreatment ionization chamber array (2%/2 mm) gamma results were also significantly correlated with on-treatment trajectory log file gamma results (R = 0.623, p < 0.001). Furthermore, all gamma results displayed a significant correlation with MCS (R > 0.57, p < 0.001), but not with MU/arc. Average MLC position and gantry angle errors were 0.001 ± 0.002 mm and 0.025° ± 0.008° over all treatment sites and were not found to affect delivery accuracy. However, vari- ability in MLC speed was found to be directly related to MLC position accuracy. The accuracy of VMAT plan delivery assessed using pretreatment trajectory log file fluence delivery and ionization chamber array measurements were strongly correlated with on-treatment trajectory log file fluence delivery. The strong corre- lation between trajectory log file and phantom-based gamma results demonstrates potential to reduce our current patient-specific QA. Additionally, insight into MLC and gantry position accuracy through trajectory log file analysis and the strong cor- relation between gamma analysis results and the MCS could also provide further methodologies to both optimize the VMAT planning and QA process. 

Excess molar volumes and excess molar enthalpies in binary systems N-alkyl-triethylammonium bis(trifluoromethylsulfonyl)imide plus methanol

In the present paper, a study on the influence of the alkyl chain length in N-alkyl-triethylammonium bis(trifluoromethylsulfonyl)imide ionic liquids, [N_R,222][Tf₂N] (R   = 6, 8 or 12), on the excess molar enthalpy at 303.15 K and excess molar volume within the temperature interval (283.15–338.15 K) of ionic liquid + methanol mixtures is carried out. Small excess molar volumes with highly asymmetric curves (i.e. S-shape) as a function of mole fraction composition were obtained, with negative values showing in the methanol-rich regions. The excess molar volumes increase with the increase of the alkyl-chain length of the ammonium cation of the ionic liquid and decrease with temperature. The excess enthalpies of selected binary mixtures are positive over the whole composition range and increase slightly with the length of the alkyl side-chain of the cation on the ionic liquid. Both excess properties were subsequently correlated using a Redlich–Kister-type equation, as well as by using the ERAS model. From this semipredictive model the studied excess quantities could be obtained from its chemical and physical contribution. Finally, the COSMOThermX software has been used to evaluate its prediction capability on the excess enthalpy for investigated mixtures at 303.15 K and 0.1 MPa. From this work, it appears that COSMOThermX method predicts this property with good accuracy of approx. 10%, providing at the same time the correct order of magnitude of the partial molar excess enthalpies at infinite dilution for the studied ILs,

High-throughput single-nucleotide polymorphism-based typing of shared Pseudomonas aeruginosa strains in cystic fibrosis patients using the Sequenom iPLEX platform

Shared strains of Pseudomonas aeruginosa are now well recognized in people with cystic fibrosis (CF), and suitable P. aeruginosa laboratory typing tools are pivotal to understanding their clinical significance and guiding infection control policies in CF clinics. We therefore compared a single-nucleotide polymorphism (SNP)-based typing method using Sequenom iPLEX matrix-assisted laser desorption ionization with time-of-flight mass spectrometry (MALDI-TOF MS) with typing methods used routinely by our laboratory. We analysed 617 P. aeruginosa isolates that included 561 isolates from CF patients collected between 2001 and 2009 in two Brisbane CF clinics and typed previously by enterobacterial repetitive intergenic consensus (ERIC)-PCR, as well as 56 isolates from non-CF patients analysed previously by multilocus sequence typing (MLST). The isolates were tested using a P. aeruginosa Sequenom iPLEX MALDI-TOF (PA iPLEX) method comprising two multiplex reactions, a 13-plex and an 8-plex, to characterize 20 SNPs from the P. aeruginosa housekeeping genes acsA, aroE, guaA, mutL, nuoD, ppsA and trpE. These 20 SNPs were employed previously in a real-time format involving 20 separate assays in our laboratory. The SNP analysis revealed 121 different SNP profiles for the 561 CF isolates. Overall, there was at least 96% agreement between the ERIC-PCR and SNP analyses for all predominant shared strains among patients attending our CF clinics: AUST-01, AUST-02 and AUST-06. For the less frequently encountered shared strain AUST-07, 6/25 (24%) ERIC-PCR profiles were misidentified initially as AUST-02 or as unique, illustrating the difficulty of gel-based analyses. SNP results for the 56 non-CF isolates were consistent with previous MLST data. Thus, the PA iPLEX format provides an attractive high-throughput alternative to ERIC-PCR for large-scale investigations of shared P. aeruginosa strains.

Antimicrobial Efficacy of an Innovative Emulsion of Medium Chain Triglycerides against Canine and Feline Periodontopathogens

OBJECTIVES: To test the in vitro antimicrobial efficacy of a non-toxic emulsion of free fatty acids against clinically relevant canine and feline periodontopathogens 
METHODS: Antimicrobial kill kinetics were established utilising an alamarBlue® viability assay against 10 species of canine and feline periodontopathogens in the biofilm mode of growth at a concentration of 0·125% v/v medium chain triglyceride (ML:8) emulsion. The results were compared with 0·12% v/v chlorhexidine digluconate and a xylitol-containing dental formulation. Mammalian cellular cytotoxicity was also investigated for both the ML:8 emulsion and chlorhexidine digluconate (0·25 to 0·0625% v/v) using in vitro tissue culture techniques.
RESULTS: No statistically significant difference was observed in the antimicrobial activity of the ML:8 emulsion and chlorhexidine digluconate; a high percentage kill rate (>70%) was achieved within 5 minutes of exposure and was maintained at subsequent time points. A statistically significant improvement in antibiofilm activity was observed with the ML:8 emulsion compared with the xylitol-containing formulation. The ML:8 emulsion possessed a significantly lower (P<0·001) toxicity profile compared with the chlorhexidine digluconate in mammalian cellular cytotoxicity assays.
CLINICAL SIGNIFICANCE: The ML:8 emulsion exhibited significant potential as a putative effective antimi-crobial alternative to chlorhexidine- and xylitol- based products for the reduction of canine and feline periodontopathogens.

Analysis of wntless (WLS) expression in gastric, ovarian, and breast cancers reveals a strong association with HER2 overexpression

The oncogenic role of WNT is well characterized. Wntless (WLS) (also known as GPR177, or Evi), a key modulator of WNT protein secretion, was recently found to be highly overexpressed in malignant astrocytomas. We hypothesized that this molecule may be aberrantly expressed in other cancers known to possess aberrant WNT signaling such as ovarian, gastric, and breast cancers. Immunohistochemical analysis using a TMA platform revealed WLS overexpression in a subset of ovarian, gastric, and breast tumors; this overexpression was associated with poorer clinical outcomes in gastric cancer (P=0.025). In addition, a strong correlation was observed between WLS expression and human epidermal growth factor receptor 2 (HER2) overexpression. Indeed, 100% of HER2-positive intestinal gastric carcinomas, 100% of HER2-positive serous ovarian carcinomas, and 64% of HER2-positive breast carcinomas coexpressed WLS protein. Although HER2 protein expression or gene amplification is an established predictive biomarker for trastuzumab response in breast and gastric cancers, a significant proportion of HER2-positive tumors display resistance to trastuzumab, which may be in part explainable by a possible mechanistic link between WLS and HER2.

Seroepidemiology of norovirus-associated travelers' diarrhea

Background: Noroviruses (NoVs) are the most common cause of epidemic gastroenteritis, responsible for at least 50% of all gastroenteritis outbreaks worldwide and were recently identified as a leading cause of travelers' diarrhea (TD) in US and European travelers to Mexico, Guatemala, and India.

Methods: Serum and diarrheic stool samples were collected from 75 US student travelers to Cuernavaca, Mexico, who developed TD. NoV RNA was detected in acute diarrheic stool samples using reverse transcription-polymerase chain reaction (RT-PCR). Serology assays were performed using GI.1 Norwalk virus (NV) and GII.4 Houston virus (HOV) virus-like particles (VLPs) to measure serum levels of immunoglobulin A (IgA) and IgG by dissociation-enhanced lanthanide fluorescent immunoassay (DELFIA); serum IgM was measured by capture enzyme-linked immunosorbent assay (ELISA), and the 50% antibody-blocking titer (BT50 ) was determined by a carbohydrate-blocking assay.

Results: NoV infection was identified in 12 (16%; 9 GI-NoV and 3 GII-NoV) of 75 travelers by either RT-PCR or fourfold or more rise in antibody titer. Significantly more individuals had detectable preexisting IgA antibodies against HOV (62/75, 83%) than against NV (49/75, 65%) (p = 0.025) VLPs. A significant difference was observed between NV- and HOV-specific preexisting IgA antibody levels (p = 0.0037), IgG (p = 0.003), and BT50 (p = <0.0001). None of the NoV-infected TD travelers had BT50  > 200, a level that has been described previously as a possible correlate of protection.

Conclusion: We found that GI-NoVs are commonly associated with TD cases identified in US adults traveling to Mexico, and seroprevalence rates and geometric mean antibody levels to a GI-NoV were lower than to a GII-NoV strain.

Susceptibility to Invasive Meningococcal Disease: Polymorphism of Complement System Genes and Neisseria meningitidis Factor H Binding Protein

BACKGROUND: Neisseria meningitidis can cause severe infection in humans. Polymorphism of Complement Factor H (CFH) is associated with altered risk of invasive meningococcal disease (IMD). We aimed to find whether polymorphism of other complement genes altered risk and whether variation of N. meningitidis factor H binding protein (fHBP) affected the risk association.

METHODS: We undertook a case-control study with 309 European cases and 5,200 1958 Birth Cohort and National Blood Service cohort controls. We used additive model logistic regression, accepting P<0.05 as significant after correction for multiple testing. The effects of fHBP subfamily on the age at infection and severity of disease was tested using the independent samples median test and Student's T test. The effect of CFH polymorphism on the N. meningitidis fHBP subfamily was investigated by logistic regression and Chi squared test.

RESULTS: Rs12085435 A in C8B was associated with odds ratio (OR) of IMD (0.35 [95% CI 0.19-0.67]; P = 0.03 after correction). A CFH haplotype tagged by rs3753396 G was associated with IMD (OR 0.56 [95% CI 0.42-0.76], P = 1.6x10-4). There was no bacterial load (CtrA cycle threshold) difference associated with carriage of this haplotype. Host CFH haplotype and meningococcal fHBP subfamily were not associated. Individuals infected with meningococci expressing subfamily A fHBP were younger than those with subfamily B fHBP meningococci (median 1 vs 2 years; P = 0.025).

DISCUSSION: The protective CFH haplotype alters odds of IMD without affecting bacterial load for affected heterozygotes. CFH haplotype did not affect the likelihood of infecting meningococci having either fHBP subfamily. The association between C8B rs12085435 and IMD requires independent replication. The CFH association is of interest because it is independent of known functional polymorphisms in CFH. As fHBP-containing vaccines are now in use, relationships between CFH polymorphism and vaccine effectiveness and side-effects may become important.

The chromosome 3q25 locus associated with fetal adiposity is not associated with childhood adiposity

Increased newborn adiposity is associated with later adverse metabolic outcomes. Previous genome-wide association studies (GWAS) demonstrated strong association of a locus on chromosome 3 (3q25.31) with newborn sum of skinfolds, a measure of overall adiposity. Whether this locus is associated with childhood adiposity is unknown. Genotype and sum of skinfolds data were available for 293 children at birth and age 2, and for 350 children at birth and age 6 from a European cohort (Belfast, UK) who participated in the Hyperglycemia and Adverse Pregnancy Outcome GWAS. We examined single nucleotide polymorphisms (SNPs) at the 3q25.31 locus associated with newborn adiposity. Linear regression analyses under an additive genetic model adjusting for maternal body mass index were performed. In both cohorts, a positive association was observed between all SNPs and sum of skinfolds at birth (P=2.3 × 10(-4), β=0.026 and P=4.8 × 10(-4), β=0.025). At the age of 2 years, a non-significant negative association was observed with sum of skinfolds (P=0.06; β =-0.015). At the age of 6 years, there was no evidence of association (P=0.86; β=0.002). The 3q25.31 locus strongly associated with newborn adiposity had no significant association with childhood adiposity suggesting that its impact may largely be limited to fetal fat accretion.

How subtle are the biases that shape the fidelity of the fossil record? A test using marine molluscs

Biases in preservation shape the fossil record, and therefore impact on our reconstructions of past environments and biodiversity. Given the intensive recent research in the general fields of taphonomy and exceptional preservation, surprisingly, fundamental questions remain unanswered about species-level variation in skeletal preservation potential at low taxonomic levels (e.g. between genera from the same family, or between taxa from related families) across myriad groups with multi-element skeletons. Polyplacophoran molluscs (chitons sensu lato) are known from the late Cambrian to Recent, and possess a distinctive articulated scleritome consisting of eight overlapping calcareous valves. The apparent uniformity of living chitons presents an ideal model to test the potential for taphonomic biases at the alpha-taxon level. The vast majority of fossil chitons are preserved as single valves; few exhibit body preservation or even an articulated shell series. An experimental taphonomic programme was conducted using the Recent polyplacophorans Lepidochitona cinerea and Tonicella marmorea (suborder Chitonina) and Acanthochitona crinita (Acanthochitonina). Experiments in a rock tumbler on disarticulated valves found differential resistance to abrasion between taxa; in one experiment 53.8-61.5% of Lepidochitona valves were recovered but 92% of those from Tonicella and 100% of elements from Acanthochitona. Chiton valves and even partly decayed carcasses are more resistant to transportation than their limited fossil record implies. Different species of living chitons have distinctly different preservation potential. This, problematically, does not correlate with obvious differences in gross valve morphology; some, but not all, of the differences correlate with phylogeny. Decay alone is sufficient to exacerbate differences in preservation potential of multi-element skeletons; some, but not all, of the variation that results is due to specimen size and the fidelity of the fossil record will thus vary intra-specifically (e.g. between ontogenetic stages) as well as inter-specifically. 

Prevalence of refractive error in Europe: the European Eye Epidemiology (E3) Consortium

To estimate the prevalence of refractive error in adults across Europe. Refractive data (mean spherical equivalent) collected between 1990 and 2013 from fifteen population-based cohort and cross-sectional studies of the European Eye Epidemiology (E³) Consortium were combined in a random effects meta-analysis stratified by 5-year age intervals and gender. Participants were excluded if they were identified as having had cataract surgery, retinal detachment, refractive surgery or other factors that might influence refraction. Estimates of refractive error prevalence were obtained including the following classifications: myopia ≤−0.75 diopters (D), high myopia ≤−6D, hyperopia ≥1D and astigmatism ≥1D. Meta-analysis of refractive error was performed for 61,946 individuals from fifteen studies with median age ranging from 44 to 81 and minimal ethnic variation (98 % European ancestry). The age-standardised prevalences (using the 2010 European Standard Population, limited to those ≥25 and <90 years old) were: myopia 30.6 % [95 % confidence interval (CI) 30.4–30.9], high myopia 2.7 % (95 % CI 2.69–2.73), hyperopia 25.2 % (95 % CI 25.0–25.4) and astigmatism 23.9 % (95 % CI 23.7–24.1). Age-specific estimates revealed a high prevalence of myopia in younger participants [47.2 % (CI 41.8–52.5) in 25–29 years-olds]. Refractive error affects just over a half of European adults. The greatest burden of refractive error is due to myopia, with high prevalence rates in young adults. Using the 2010 European population estimates, we estimate there are 227.2 million people with myopia across Europe.

Inland shell midden site-formation:Investigation into a late Pleistocene to early Holocene midden from Trang An, Northern Vietnam

Over the course of the past two decades there has been growing research interest in the site formation processes of shell middens. This stands along-side and is being used to inform cultural, dietary and palaeo-environmental reconstructions. Just as midden site formation processes have turned out to be many and varied, however, the kinds of shell-bearing sites that past human communities created are likely to have been no less diverse. Subsuming such sites under a single category - shell middens - normalises that variation and may lead to the misinterpretation of site function. The greater part of research in this field also continues to focus on coastal shell middens; comparatively little attention has been paid to middens containing freshwater and especially terrestrial molluscs from hinterland locations. As a result, much of the current understanding about shell-midden sites carries a spatial as well as a functional bias. This paper hopes to contribute towards discussion on both fronts. It presents a detailed examination of the formation processes that went into the creation of a land snail-dominated late- to post-glacial midden from northern Vietnam, and considers the role that it may have played in the early settlement of this area. The data presented comes from ongoing archaeological excavations at Hang Boi, a cave located in the sub-coastal karstic uplands of Trang An park, in the Vietnamese Province of Ninh Binh. (C) 2010 Elsevier Ltd and INQUA. All rights reserved.

Predicting low velocity impact damage and Compression-After-Impact (CAI) behaviour of composite laminates

Low-velocity impact damage can drastically reduce the residual strength of a composite structure even when the damage is barely visible. The ability to computationally predict the extent of damage and compression-after-impact (CAI) strength of a composite structure can potentially lead to the exploration of a larger design space without incurring significant time and cost penalties. A high-fidelity three-dimensional composite damage model, to predict both low-velocity impact damage and CAI strength of composite laminates, has been developed and implemented as a user material subroutine in the commercial finite element package, ABAQUS/Explicit. The intralaminar damage model component accounts for physically-based tensile and compressive failure mechanisms, of the fibres and matrix, when subjected to a three-dimensional stress state. Cohesive behaviour was employed to model the interlaminar failure between plies with a bi-linear traction–separation law for capturing damage onset and subsequent damage evolution. The virtual tests, set up in ABAQUS/Explicit, were executed in three steps, one to capture the impact damage, the second to stabilize the specimen by imposing new boundary conditions required for compression testing, and the third to predict the CAI strength. The observed intralaminar damage features, delamination damage area as well as residual strength are discussed. It is shown that the predicted results for impact damage and CAI strength correlated well with experimental testing without the need of model calibration which is often required with other damage models.

Evolution of microstructure and changes of mechanical properties of CLAM steel after long-term aging

The China Low Activation Martensitic (CLAM) steel has been developed as a candidate structural material for future fusion reactors. It is essential to investigate the evolution of microstructure and changes of mechanical properties of CLAM steel during thermal exposure. In this study, the long-term thermal aging of the CLAM steel has been carried out in air at 600 °C and 650 °C for 1100 h, 3000 h and 5000 h. The microstructural evolution with aging time was studied, including characteristics of the growth of M23C6 carbides and the formation of Laves-phase precipitates as well as the evolved subgrains. The microstructural evolution leads to the changes of mechanical properties of the CLAM steel. The Ductile–Brittle Transition Temperature (DBTT) increases significantly during the thermal aging, which is related to the formation of Laves-phase in the steel matrix. The possible mechanism of stabilizing microstructure during the thermal exposure has been analyzed based on the interaction between M23C6 carbides and subgrain boundaries.

The effect of melt viscosity on thermal efficiency for single screw extrusion of HDPE

In this work, a highly instrumented single screw extruder has been used to study the effect of polymer rheology on the thermal efficiency of the extrusion process. Three different molecular weight grades of high density polyethylene (HDPE) were extruded at a range of conditions. Three geometries of extruder screws were used at several set temperatures and screw rotation speeds. The extruder was equipped with real-time quantification of energy consumption; thermal dynamics of the process were examined using thermocouple grid sensors at the entrance to the die. Results showed that polymer rheology had a significant effect on process energy consumption and thermal homogeneity of the melt. Highest specific energy consumption and poorest homogeneity was observed for the highest viscosity grade of HDPE. Extruder screw geometry, set extrusion temperature and screw rotation speed were also found to have a direct effect on energy consumption and melt consistency. In particular, specific energy consumption was lower using a barrier flighted screw compared to single flighted screws at the same set conditions. These results highlight the complex nature of extrusion thermal dynamics and provide evidence that rheological properties of the polymer can significantly influence the thermal efficiency of the process.

Facile synthesis of nanocrystalline LiFePO4/graphene composite as cathode material for high power lithium ion batteries

We describe a simple strategy, which is based on the idea of space confinement, for the synthesis of carbon coating on LiFePO₄ nanoparticles/graphene nanosheets composites in a water-in-oil emulsion system. The prepared composite displayed high performance as a cathode material for lithium-ion battery, such as high reversible lithium storage capacity (158 mA h g^-1 after 100 cycles), high coulombic efficiency (over 97%), excellent cycling stability and high rate capability (as high as 83 mA h g ^-1 at 60 C). Very significantly, the preparation method employed can be easily adapted and be extended as a general approach to sophisticated compositions and structures for the preparation of highly dispersed nanosized structure on graphene.