An integrated 3D printed radioluminescent-based phantom for quality assurance on a robotic-arm linac.

Objective. To develop, characterize and improve upon a high-resolution 3D printed radioluminescence-based imaging phantom for quality assurance (QA) of a robotic arm linear accelerator.Approach. A phantom was constructed which consisted of a scintillating sheet, fiducial markers, a low-cost complementary metal-oxide semiconductor camera and a 3D printed light-tight enclosure. The camera, equipped with a 12 mm lens, was angled 45 degrees from the horizontal axis with a direct line of sight of the scintillating sheet. A perspective image transformation with optical distortion correction was employed to obtain beam's eye view images for different collimators. Beam profiles, Iris™ field size, multileaf collimator leaf positioning and central laser-radiation field coincidence QA tests were performed and compared against data obtained with gafchromic film. The phantom's short-term stability, sensitivity to changes in output, field size and leaf positioning were also assessed.Main Results. The limiting resolution of the optical system was measured to be ∼0.26 mm. Field size, as measured by the radioluminescence system for Iris apertures, agreed to within 0.2 mm of the values measured using film. The imaging system was sensitive to field size changes well below 0.2 mm and output changes as small as 1 monitor unit (MU). For the optical setup, the mean leaf deviation error for banksX1 andX2 was 0.21 and 0.17 mm at 800 mm source to axis distance, whereas the mean difference for the film dataset was 0.16 mm and 0.22 mm for banksX1 andX2, respectively. The optical system was able to detect leaf positioning errors as small as 0.2 mm. Compared with film data, excellent agreement was seen for relative central axis beam profiles for 10 mm and 5 mm beams.Significance. The phantom presented here is an alternative to film and electronic portal imager devices, due to its low-cost, portability, and high spatial and temporal resolution.

A Step Toward Making VMAT TBI More Prevalent: Automating the Treatment Planning Process.

PURPOSE: Our purpose was to automate the treatment planning process for total body irradiation (TBI) with volumetric modulated arc therapy (VMAT). METHODS AND MATERIALS: Two scripts were developed to facilitate autoplanning: the binary plug-in script automating the creation of optimization structures, plan generation, beam placement, and setting of the optimization constraints and the stand-alone executable performing successive optimizations. Ten patients previously treated in our clinic with VMAT TBI were used to evaluate the efficacy of the proposed autoplanning process. Paired t tests were used to compare the dosimetric indices of the produced auto plans to the manually generated clinical plans. In addition, 3 physicians were asked to evaluate the manual and autoplans for each patient in a blinded retrospective review. RESULTS: No significant differences were observed between the manual and autoplan global Dmax (P < .893), planning target volume V110% (P < .734), kidneys Dmean (P < .351), and bowel Dmax (P < .473). Significant decreases in the Dmean to the lungs and lungs-1cm (ie, lungs with 1-cm inner margin) volumes of 5.4% ± 6.4% (P < .024) and 6.8% ± 7.4% (P < .017), respectively, were obtained with the autoplans compared with the manual plans. The autoplans were selected 77% of the time by the reviewing physicians as equivalent or superior to the manual plans. The required time for treatment planning was estimated to be 2 to 3 days for the manual plans compared with approximately 3 to 5 hours for the autoplans. CONCLUSIONS: Large reductions in planning time without sacrificing plan quality were obtained using the developed autoplanning process compared with manual planning, thus reducing the required effort of the treatment planning team. Superior lung sparing with the same target coverage and similar global Dmax were observed with the autoplans as compared with the manual treatment plans. The developed scripts have been made open-source to improve access to VMAT TBI at other institutions and clinics.

Drain Usage in Head and Neck Surgery: A National Survey of Thirty-five Surgeons across Ten Units

Introduction Drain usage is commonplace in head and neck surgery. There is an increasing body of literature disputing their routine placement in certain procedures. The aim of this study is to explore modern-day practice in terms of drain usage and the use of haemostatic agents. Methods A simple questionnaire was devised and sent to 35 ENT Surgeons across 10 units nationally. Results There was an overall response rate of 77.1% (n=27). There was considerable heterogeneity amongst surgeons in terms of indication for insertion, how the decision is made to remove the drain and if any alternative/adjunctive haemostatic agents are being used. Discussion The management of drains is poorly defined and guidelines are lacking. With increased pressure on resources, the risk of infection and discomfort to the patient, further reflection is required to evaluate if careful patient selection rather than habitual drain insertion in every case is more appropriate.

Enhanced climate instability in the North Atlantic and southern Europe during the Last Interglacial.

Considerable ambiguity remains over the extent and nature of millennial/centennial-scale climate instability during the Last Interglacial (LIG). Here we analyse marine and terrestrial proxies from a deep-sea sediment sequence on the Portuguese Margin and combine results with an intensively dated Italian speleothem record and climate-model experiments. The strongest expression of climate variability occurred during the transitions into and out of the LIG. Our records also document a series of multi-centennial intra-interglacial arid events in southern Europe, coherent with cold water-mass expansions in the North Atlantic. The spatial and temporal fingerprints of these changes indicate a reorganization of ocean surface circulation, consistent with low-intensity disruptions of the Atlantic meridional overturning circulation (AMOC). The amplitude of this LIG variability is greater than that observed in Holocene records. Episodic Greenland ice melt and runoff as a result of excess warmth may have contributed to AMOC weakening and increased climate instability throughout the LIG.

Corium lavas: structure and properties of molten UO2-ZrO2 under meltdown conditions.

In the exceedingly rare event of nuclear reactor core meltdown, uranium dioxide fuel reacts with Zircaloy cladding to produce eutectic melts which can subsequently be oxidized by coolant/moderator water. Oxidized corium liquids in the xUO2·(100 - x)ZrO2 system were produced via laser melting of UO2-ZrO2 mixtures to temperatures in excess of 3000 K. Contamination was avoided by floating the droplets on a gas stream within an aerodynamic levitator and in-situ high-energy x-ray diffraction experiments allowed structural details to be elucidated. Molecular dynamics simulations well reproduced diffraction and density data, and show less compositional variation in thermal expansion and viscosity than suggested by existing measurements. As such, corium liquids maintain their highly penetrating nature irrespective of the amount of oxidized cladding dissolved in the molten fuel. Metal-oxygen coordination numbers vary with both composition and temperature. The former is due to mismatch in native values, nUO(x = 100) ≈ 7 and nZrO(x = 0) ≈ 6, and the requirement for oxygen site stabilization. The latter provides a thermal expansion mechanism.

Radiocarbon constraints on the glacial ocean circulation and its impact on atmospheric CO2.

While the ocean's large-scale overturning circulation is thought to have been significantly different under the climatic conditions of the Last Glacial Maximum (LGM), the exact nature of the glacial circulation and its implications for global carbon cycling continue to be debated. Here we use a global array of ocean-atmosphere radiocarbon disequilibrium estimates to demonstrate a ∼689±53 14C-yr increase in the average residence time of carbon in the deep ocean at the LGM. A predominantly southern-sourced abyssal overturning limb that was more isolated from its shallower northern counterparts is interpreted to have extended from the Southern Ocean, producing a widespread radiocarbon age maximum at mid-depths and depriving the deep ocean of a fast escape route for accumulating respired carbon. While the exact magnitude of the resulting carbon cycle impacts remains to be confirmed, the radiocarbon data suggest an increase in the efficiency of the biological carbon pump that could have accounted for as much as half of the glacial-interglacial CO2 change.

Revisiting the hydration structure of aqueous Na.

A combination of theory, X-ray diffraction (XRD) and extended x-ray absorption fine structure (EXAFS) are used to probe the hydration structure of aqueous Na+. The high spatial resolution of the XRD measurements corresponds to Qmax = 24 Å-1 while the first-reported Na K-edge EXAFS measurements have a spatial resolution corresponding to 2k = Qmax = 16 Å-1. Both provide an accurate measure of the shape and position of the first peak in the Na-O pair distribution function, gNaO(r). The measured Na-O distances of 2.384 ± 0.003 Å (XRD) and 2.37 ± 0.024 Å (EXAFS) are in excellent agreement. These measurements show a much shorter Na-O distance than generally reported in the experimental literature (Na-Oavg ∼ 2.44 Å) although the current measurements are in agreement with recent neutron diffraction measurements. The measured Na-O coordination number from XRD is 5.5 ± 0.3. The measured structure is compared with both classical and first-principles density functional theory (DFT) simulations. Both of the DFT-based methods, revPBE and BLYP, predict a Na-O distance that is too long by about 0.05 Å with respect to the experimental data (EXAFS and XRD). The inclusion of dispersion interactions (-D3 and -D2) significantly worsens the agreement with experiment by further increasing the Na-O distance by 0.07 Å. In contrast, the use of a classical Na-O Lennard-Jones potential with SPC/E water accurately predicts the Na-O distance as 2.39 Å although the Na-O peak is over-structured with respect to experiment.

Radiocarbon evidence for enhanced respired carbon storage in the Atlantic at the Last Glacial Maximum.

The influence of ocean circulation changes on atmospheric CO2 hinges primarily on the ability to alter the ocean interior's respired nutrient inventory. Here we investigate the Atlantic overturning circulation at the Last Glacial Maximum and its impact on respired carbon storage using radiocarbon and stable carbon isotope data from the Brazil and Iberian Margins. The data demonstrate the existence of a shallow well-ventilated northern-sourced cell overlying a poorly ventilated, predominantly southern-sourced cell at the Last Glacial Maximum. We also find that organic carbon remineralization rates in the deep Atlantic remained broadly similar to modern, but that ventilation ages in the southern-sourced overturning cell were significantly increased. Respired carbon storage in the deep Atlantic was therefore enhanced during the last glacial period, primarily due to an increase in the residence time of carbon in the deep ocean, rather than an increase in biological carbon export.

The structure of liquid water up to 360 MPa from x-ray diffraction measurements using a high Q-range and from molecular simulation.

X-ray diffraction measurements of liquid water are reported at pressures up to 360 MPa corresponding to a density of 0.0373 molecules per Å(3). The measurements were conducted at a spatial resolution corresponding to Q(max) = 16 Å(-1). The method of data analysis and measurement in this study follows the earlier benchmark results reported for water under ambient conditions having a density of 0.0333 molecules per Å(3) and Q(max) = 20 Å(-1) [J. Chem. Phys. 138, 074506 (2013)] and at 70 °C having a density of 0.0327 molecules per Å(3) and Q(max) = 20 Å(-1) [J. Chem. Phys. 141, 214507 (2014)]. The structure of water is very different at these three different T and P state points and thus they provide the basis for evaluating the fidelity of molecular simulation. Measurements show that at 360 MPa, the 4 waters residing in the region between 2.3 and 3 Å are nearly unchanged: the peak position, shape, and coordination number are nearly identical to their values under ambient conditions. However, in the region above 3 Å, large structural changes occur with the collapse of the well-defined 2nd shell and shifting of higher shells to shorter distances. The measured structure is compared to simulated structure using intermolecular potentials described by both first-principles methods (revPBE-D3) and classical potentials (TIP4P/2005, MB-pol, and mW). The DFT-based, revPBE-D3, method and the many-body empirical potential model, MB-pol, provide the best overall representation of the ambient, high-temperature, and high-pressure data. The revPBE-D3, MB-pol, and the TIP4P/2005 models capture the densification mechanism, whereby the non-bonded 5th nearest neighbor molecule, which partially encroaches the 1st shell at ambient pressure, is pushed further into the local tetrahedral arrangement at higher pressures by the more distant molecules filling the void space in the network between the 1st and 2nd shells.

Intravesical treatment of advanced urothelial bladder cancers with oncolytic HSV-1 co-regulated by differentially expressed microRNAs.

Urothelial bladder cancer is the most common malignancy of the urinary tract. Although most cases are initially diagnosed as non-muscle-invasive, more than 80% of patients will develop recurrent or metastatic tumors. No effective therapy exists currently for late-stage metastatic tumors. By intravesical application, local administration of oncolytic Herpes Simplex virus (oHSV-1) can provide a promising new therapy for this disease. However, its inherent neurotoxicity has been a perceived limitation for such application. In this study, we present a novel microRNA-regulatory approach to reduce HSV-1-induced neurotoxicity by suppressing viral replication in neurons while maintaining oncolytic selectivity toward urothelial tumors. Specifically, we designed a recombinant virus that utilizes differentially expressed endogenous microR143 (non-cancerous, ubiquitous) and microR124 (neural-specific) to regulate expression of ICP-4, a gene essential for HSV-1 replication. We found that expression of ICP-4 must be controlled by a combination of both miR143 and miR124 to achieve the most effective attenuation in HSV-1-induced toxicity while retaining maximal oncolytic capacity. These results suggest that interaction between miR143 and miR124 may be required to successfully regulate HSV-1 replication. Our resent study is the first proof-in-principle that miRNA combination can be exploited to fine-tune the replication of HSV-1 to treat human cancers.

Topological ordering in liquid UO2.

A molecular dynamics model of liquid UO2 that is in good agreement with recent high-energy x-ray diffraction data has been analyzed using the Bhatia-Thornton formalism. A pre-peak appears in the topological structure factor S NN(Q) at Q = 1.85(1)Å(-1) which is not present in the more common, element specific Faber-Ziman partial structure factors. A radical Voronoi tessellation of the 3D molecular dynamics model shows the presence of a wide distribution of clusters, consistent with presence of highly mobile oxygen atoms. However, 4-fold Voronoi polyhedra (n 4) are found to dominate the structure and the majority of clusters can be described by the distribution n 3 ⩽ n 4 ⩾ n 5. It is argued that an open network of 4-fold Voronoi polyhedra could explain the origin of the pre-peak in S NN(Q) and the topological ordering observed in liquid UO2.

Note: Detector collimators for the nanoscale ordered materials diffractometer instrument at the Spallation Neutron Source.

Five neutron collimator designs were constructed and tested at the nanoscale ordered materials diffractometer (NOMAD) instrument. Collimators were made from High Density PolyEthylene (HDPE) or 5% borated HDPE. In all cases, collimators improved the signal to background ratio and reduced detection of secondary scattering. In the Q-range 10-20 Å(-1), signal to background ratio improved by factors of approximately 1.6 and 2.0 for 50 and 100 mm deep collimators, respectively. In the Q-range 40-50 Å(-1), the improvement factors were 1.8 and 2.7. Secondary scattering as measured at Q ∼ 9.5 Å(-1) was significantly decreased when the collimators were installed.

PALEOCEANOGRAPHY. A warm and poorly ventilated deep Arctic Mediterranean during the last glacial period.

Changes in the formation of dense water in the Arctic Ocean and Nordic Seas [the "Arctic Mediterranean" (AM)] probably contributed to the altered climate of the last glacial period. We examined past changes in AM circulation by reconstructing radiocarbon ventilation ages of the deep Nordic Seas over the past 30,000 years. Our results show that the glacial deep AM was extremely poorly ventilated (ventilation ages of up to 10,000 years). Subsequent episodic overflow of aged water into the mid-depth North Atlantic occurred during deglaciation. Proxy data also suggest that the deep glacial AM was ~2° to 3°C warmer than modern temperatures; deglacial mixing of the deep AM with the upper ocean thus potentially contributed to the melting of sea ice, icebergs, and terminal ice-sheet margins.

The structure of water around the compressibility minimum.

Here we present diffraction data that yield the oxygen-oxygen pair distribution function, g(OO)(r) over the range 254.2-365.9 K. The running O-O coordination number, which represents the integral of the pair distribution function as a function of radial distance, is found to exhibit an isosbestic point at 3.30(5) Å. The probability of finding an oxygen atom surrounding another oxygen at this distance is therefore shown to be independent of temperature and corresponds to an O-O coordination number of 4.3(2). Moreover, the experimental data also show a continuous transition associated with the second peak position in g(OO)(r) concomitant with the compressibility minimum at 319 K.

Molten uranium dioxide structure and dynamics.

Uranium dioxide (UO2) is the major nuclear fuel component of fission power reactors. A key concern during severe accidents is the melting and leakage of radioactive UO2 as it corrodes through its zirconium cladding and steel containment. Yet, the very high temperatures (>3140 kelvin) and chemical reactivity of molten UO2 have prevented structural studies. In this work, we combine laser heating, sample levitation, and synchrotron x-rays to obtain pair distribution function measurements of hot solid and molten UO2. The hot solid shows a substantial increase in oxygen disorder around the lambda transition (2670 K) but negligible U-O coordination change. On melting, the average U-O coordination drops from 8 to 6.7 ± 0.5. Molecular dynamics models refined to this structure predict higher U-U mobility than 8-coordinated melts.

Ultrafast X-ray probing of water structure below the homogeneous ice nucleation temperature.

Water has a number of anomalous physical properties, and some of these become drastically enhanced on supercooling below the freezing point. Particular interest has focused on thermodynamic response functions that can be described using a normal component and an anomalous component that seems to diverge at about 228 kelvin (refs 1-3). This has prompted debate about conflicting theories that aim to explain many of the anomalous thermodynamic properties of water. One popular theory attributes the divergence to a phase transition between two forms of liquid water occurring in the 'no man's land' that lies below the homogeneous ice nucleation temperature (TH) at approximately 232 kelvin and above about 160 kelvin, and where rapid ice crystallization has prevented any measurements of the bulk liquid phase. In fact, the reliable determination of the structure of liquid water typically requires temperatures above about 250 kelvin. Water crystallization has been inhibited by using nanoconfinement, nanodroplets and association with biomolecules to give liquid samples at temperatures below TH, but such measurements rely on nanoscopic volumes of water where the interaction with the confining surfaces makes the relevance to bulk water unclear. Here we demonstrate that femtosecond X-ray laser pulses can be used to probe the structure of liquid water in micrometre-sized droplets that have been evaporatively cooled below TH. We find experimental evidence for the existence of metastable bulk liquid water down to temperatures of 227(-1)(+2) kelvin in the previously largely unexplored no man's land. We observe a continuous and accelerating increase in structural ordering on supercooling to approximately 229 kelvin, where the number of droplets containing ice crystals increases rapidly. But a few droplets remain liquid for about a millisecond even at this temperature. The hope now is that these observations and our detailed structural data will help identify those theories that best describe and explain the behaviour of water.

Low cation coordination in oxide melts.

The complete set of partial pair distribution functions for a rare earth oxide liquid are measured by combining aerodynamic levitation, neutron and x-ray diffraction on Y2O3, and Ho2O3 melts at 2870 K. The average Y-O (or Ho-O) coordination of these isomorphic melts is measured to be 5.5(2), which is significantly less than the octahedral coordination of crystalline Y2O3 (or Ho2O3). Investigation of La2O3, ZrO2, and Al2O3 melts by x-ray diffraction and molecular dynamics simulations also show lower-than-crystal cation-oxygen coordination. These measurements suggest a general trend towards lower coordination compared to their crystalline counterparts. It is found that the coordination drop is larger for lower field strength, larger radius cations and is negligible for high field strength (network forming) cations, such as SiO2. These findings have broad implications for predicting the local structure and related physical properties of metal-oxide melts and oxide glasses.

Impact of nursery feeding program on subsequent growth performance, carcass quality, meat quality, and physical and chemical body composition of growing-finishing pigs.

An experiment was conducted to examine the effect of the nursery feeding program on subsequent growth performance, carcass quality, meat quality, and physical and chemical body composition of growing-finishing pigs. Four dietary treatments were used in a 2 × 2 factorial arrangement of treatments based on diet complexity (Complex vs. Simple) and in-feed antibiotics (2,730 [+AB] vs. 0 [-AB] mg of chlortetracycline /kg].A total of 552 pigs, in 5 blocks, were weaned at 21 ± 2 d of age with an initial BW of 7.03 ± 0.07 kg. Each experimental block had 3 pens per treatment, with 8 pigs per pen in blocks 1 and 2, and 10 pigs per pen in the remaining 3 blocks. Nursery diets were fed in a 3-phase feeding program (Phase I, II, and III diets fed for 1, 2, and 3 wk, respectively). All pigs were fed common grower-finisher diets thereafter. Six pigs per treatment were slaughtered for chemical body composition analysis at wk 2, 8, 12, and 17 postweaning. An additional 11 pigs per treatment were slaughtered at wk 17 postweaning (approximately 115 kg BW or market weight) for analysis of carcass characteristics, chemical and physical body composition, and meat quality. During the nursery phase, ADG was lower (P < 0.05) for pigs fed the Simple diet than those fed the Complex diet (491 vs. 528 g/d). Antibiotic usage improved (P < 0.05) ADG in Phases II (408 vs. 438 g/d) and III (689 vs. 720 g/d). In Phase I and II, G:F was lower (P < 0.05) for pigs fed the Simple diet than those fed the Complex diet (0.46 vs. 0.58 and 0.75 vs. 0.78 in Phases I and II, respectively). During the grower phase, pigs previously fed -AB diets grew faster than pigs fed +AB diets (P < 0.05; 1,009 vs. 971 g/d). There were no treatment effects on overall ADG or G:F from weaning to finishing. Nursery feeding program did not affect carcass quality characteristics. However, pigs previously fed +AB diets tended (P = 0.07) to have increased LM depth. Nursery feeding program had no effect on objective or subjective meat quality measures, chemical body composition, or the weight of primal and retail carcass cuts at wk 17 postweaning, with the exception of primal belly weight. These results indicate that feeding simple nursery diets, or nursery diets without antibiotics, compromises growth performance during the nursery period but does not affect overall growth performance between weaning and market BW, carcass characteristics, and meat quality. Thus, feed costs for nursery pigs can be reduced by feeding simple diets without compromising market BW and carcass and meat quality.

A time resolved high energy X-ray diffraction study of cooling liquid SiO2.

The evolution of the X-ray structure factor and corresponding pair distribution function of SiO2 has been measured upon cooling from the melt using high energy X-ray diffraction combined with aerodynamic levitation. Small changes in the position of the average Si-O bond distance and peak width are found to occur at ~1500(100) K in the region of the calorimetric glass transition temperature, T(g) and the observed density minima. At higher temperatures deviations from linear behavior are seen in the first sharp diffraction peak width, height and area at around 1750(50) K, which coincides with the reported density maximum around 1.2T(g).

Structure of molten CaSiO3: neutron diffraction isotope substitution with aerodynamic levitation and molecular dynamics study.

We have performed neutron diffraction isotopic substitution experiments on aerodynamically levitated droplets of CaSiO(3), to directly extract intermediate and local structural information on the Ca environment. The results show a substantial broadening of the first Ca-O peak in the pair distribution function of the melt compared to the glass, which comprises primarily of 6- and 7-fold coordinated Ca-polyhedra. The broadening can be explained by a redistribution of Ca-O bond lengths, especially toward longer distances in the liquid. The first order neutron difference function provides a test of recent molecular dynamics simulations and supports the MD model which contains short chains or channels of edge shared Ca-octahedra in the liquid state. It is suggested that the polymerization of Ca-polyhedra is responsible for the fragile viscosity behavior of the melt and the glass forming ability in CaSiO(3).