A Neutron Diffraction and Molecular Dynamics Investigation of Acetate-based Ionic Liquids as Solvents for Glucose

The liquid state structure of the ionic liquid, 1-ethyl-3-methylimidazolium acetate, and the solute/solvent structure of glucose dissolved in the ionic liquid at a 1: 6 molar ratio have been investigated at 323 K by molecular dynamics simulations and neutron diffraction experiments using H/D isotopically substituted materials. Interactions between hydrogen-bond donating cation sites and polar, directional hydrogen-bond accepting acetate anions are examined. Ion-ion radial distribution functions for the neat ionic liquid, calculated from both MD and derived from the empirical potential structure refinement model to the experimental data, show the alternating shell-structure of anions around the cation, as anticipated. Spatial probability distributions reveal the main anion-to-cation features as in-plane interactions of anions with imidazolium ring hydrogens and cation-cation planar stacking. Interestingly, the presence of the polarised hydrogen-bond acceptor anion leads to increased anion-anion tail-tail structuring within each anion shell, indicating the onset of hydrophobic regions within the anion regions of the liquid.

Structure of molten 1,3-dimethylimidazolium chloride using neutron diffraction

The model room temperature ionic liquid, 1,3-dimethylimidazolium chloride, has been studied by neutron diffraction for the first time. The diffraction data are used to derive a structural model of this liquid using Empirical Potential Structure Refinement. The model obtained indicates that significant charge ordering is present in the liquid salt and that the local order in this liquid closely resembles that found in the solid state. As in the crystal structure, hydrogen-bonding interactions between the ring hydrogens and the chloride dominate the structure. The model is compared with the data reported previously for both simple alkyl substituted imidazolium halides and binary mixtures with AlCl3. (C) 2003 American Institute of Physics.

Roche Tomography of the Secondary Stars in CVS

The secondary stars in cataclysmic variables (CVs) are key to our understanding of the origin evolution and behaviour of this class of interacting binary. In seeking a fuller understanding of these objects the challenge for observers is to obtain images of the secondary star. This goal can be achieved through Roche tomography an indirect imaging technique that can be used to map the Roche-lobe-filling secondary star. The review begins with a description of the basic principles that underpin Roche tomography including methods for determining the binary system parameters. Noise propagation onto Roche tomograms is also covered. Finally the review concludes with a look at the main scientific highlights to date and the future prospects for Roche tomography

Investigating the Potential Impact of Four-dimensional Computed Tomography (4DCT) on Toxicity, Outcomes and Dose Escalation for Radical Lung Cancer Radiotherapy

AIMS: To investigate the potential dosimetric and clinical benefits predicted by using four-dimensional computed tomography (4DCT) compared with 3DCT in the planning of radical radiotherapy for non-small cell lung cancer.

MATERIALS AND METHODS:
Twenty patients were planned using free breathing 4DCT then retrospectively delineated on three-dimensional helical scan sets (3DCT). Beam arrangement and total dose (55 Gy in 20 fractions) were matched for 3D and 4D plans. Plans were compared for differences in planning target volume (PTV) geometrics and normal tissue complication probability (NTCP) for organs at risk using dose volume histograms. Tumour control probability and NTCP were modelled using the Lyman-Kutcher-Burman (LKB) model. This was compared with a predictive clinical algorithm (Maastro), which is based on patient characteristics, including: age, performance status, smoking history, lung function, tumour staging and concomitant chemotherapy, to predict survival and toxicity outcomes. Potential therapeutic gains were investigated by applying isotoxic dose escalation to both plans using constraints for mean lung dose (18 Gy), oesophageal maximum (70 Gy) and spinal cord maximum (48 Gy).

RESULTS:
4DCT based plans had lower PTV volumes, a lower dose to organs at risk and lower predicted NTCP rates on LKB modelling (P < 0.006). The clinical algorithm showed no difference for predicted 2-year survival and dyspnoea rates between the groups, but did predict for lower oesophageal toxicity with 4DCT plans (P = 0.001). There was no correlation between LKB modelling and the clinical algorithm for lung toxicity or survival. Dose escalation was possible in 15/20 cases, with a mean increase in dose by a factor of 1.19 (10.45 Gy) using 4DCT compared with 3DCT plans.

CONCLUSIONS:
4DCT can theoretically improve therapeutic ratio and dose escalation based on dosimetric parameters and mathematical modelling. However, when individual characteristics are incorporated, this gain may be less evident in terms of survival and dyspnoea rates. 4DCT allows potential for isotoxic dose escalation, which may lead to improved local control and better overall survival.

Defining Target Volumes for Stereotactic Ablative Radiotherapy of Early-stage Lung Tumours:A Comparison of Three-dimensional F-fluorodeoxyglucose Positron Emission Tomography and Four-dimensional Computed Tomography

Aims: High local control rates are achieved in stage I lung cancer using stereotactic ablative radiotherapy. Target delineation is commonly based on four-dimensional computed tomography (CT) scans. Target volumes defined by positron emission tomography/computed tomography (PET/CT) are compared with those defined by four-dimensional CT and conventional ('three-dimensional') F-fluorodeoxyglucose (F-FDG) PET/CT. Materials and methods: For 16 stage I non-small cell lung cancer tumours, six approaches for deriving PET target volumes were evaluated: manual contouring, standardised uptake value (SUV) absolute threshold of 2.5, 35% of maximum SUV (35%SUV), 41% of SUV (41%SUV) and two different source to background ratio techniques (SBR-1 and SBR-2). PET-derived target volumes were compared with the internal target volume (ITV) from the modified maximum intensity projection (MIP ITV). Volumetric and positional correlation was assessed using the Dice similarity coefficient (DSC). Results: PET-based target volumes did not correspond to four-dimensional CT-based target volumes. The mean DSC relative to MIP ITV were: PET manual = 0.64, SUV2.5 = 0.64, 35%SUV = 0.63, 41%SUV = 0.57. SBR-1 = 0.52, SBR-2 = 0.49. PET-based target volumes were smaller than corresponding MIP ITVs. Conclusions: Conventional three-dimensional F-FDG PET-derived target volumes for lung stereotactic ablative radiotherapy did not correspond well with those derived from four-dimensional CT, including those in routine clinical use (MIP ITV). Caution is required in using three-dimensional PET for motion encompassing target volume delineation. © 2012 The Royal College of Radiologists.

The mediastinal staging accuracy of 18F-Fluorodeoxyglycose Positron Emission Tomography/Computed Tomography in non-small cell lung cancer with variable time intervals to surgery.

BACKGROUND: PET/CT scanning can determine suitability for curative therapy and inform decision making when considering radical therapy in patients with non-small cell lung cancer (NSCLC). Metastases to central mediastinal lymph nodes (N2) may alter such management decisions. We report a 2 year retrospective series assessing N2 lymph node staging accuracy with PET/CT compared to pathological analysis at surgery.

METHODS: Patients with NSCLC attending our centre (excluding those who had induction chemotherapy) who had staging PET/CT scans and pathological nodal sampling between June 2006 and June 2008 were analysed. For each lymph node assessed pathologically, the corresponding PET/CT status was determined. 64 patients with 200 N2 lymph nodes were analysed.

RESULTS: Sensitivity of PET/CT scans for indentifying involved N2 lymph nodes was
39%, specificity 96% and overall accuracy 90%. For individual lymph node analysis, logistic regression demonstrated a significant linear association between PET/CT sensitivity and time from scanning to surgery (p=0.031) but not for specificity and accuracy. Those scanned <9 weeks before pathological sampling were significantly more sensitive (64% >9 weeks, 0% ≥ 9 weeks, p=0.013) and more accurate (94% <9 weeks, 81% ≥ 9 weeks, p=0.007). Differences in specificity were not seen (97% <9 weeks, 91% ≥ 9 weeks, p=0.228). No significant difference in specificity was found at any time point.

CONCLUSIONS: We recommend that if a PET/CT scan is older than 9 weeks, and management would be altered by the presence of N2 nodes, re-staging of the
mediastinum should be undertaken.

Defining target volumes for stereotactic ablative radiotherapy of early-stage lung tumours: a comparison of three-dimensional 18F-fluorodeoxyglucose positron emission tomography and four-dimensional computed tomography.:PETCT versus 4DCT for SABR in Early Stage NSCLC

AIMS: High local control rates are achieved in stage I lung cancer using
stereotactic ablative radiotherapy. Target delineation is commonly based on
four-dimensional computed tomography (CT) scans. Target volumes defined by
positron emission tomography/computed tomography (PET/CT) are compared with those defined by four-dimensional CT and conventional ('three-dimensional')
(18)F-fluorodeoxyglucose ((18)F-FDG) PET/CT.

MATERIALS AND METHODS: For 16 stage I non-small cell lung cancer tumours, six
approaches for deriving PET target volumes were evaluated: manual contouring,
standardised uptake value (SUV) absolute threshold of 2.5, 35% of maximum SUV
(35%SUV(MAX)), 41% of SUV(MAX) (41%SUV(MAX)) and two different source to
background ratio techniques (SBR-1 and SBR-2). PET-derived target volumes were compared with the internal target volume (ITV) from the modified maximum
intensity projection (MIP(MOD) ITV). Volumetric and positional correlation was
assessed using the Dice similarity coefficient (DSC).

RESULTS: PET-based target volumes did not correspond to four-dimensional CT-based target volumes. The mean DSC relative to MIP(MOD) ITV were: PET manual = 0.64, SUV2.5 = 0.64, 35%SUV(MAX) = 0.63, 41%SUV(MAX) = 0.57. SBR-1 = 0.52, SBR-2 =0.49. PET-based target volumes were smaller than corresponding MIP ITVs.

CONCLUSIONS: Conventional three-dimensional (18)F-FDG PET-derived target volumes for lung stereotactic ablative radiotherapy did not correspond well with those derived from four-dimensional CT, including those in routine clinical use
(MIP(MOD) ITV). Caution is required in using three-dimensional PET for motion
encompassing target volume delineation.

The spotty donor star in the X-ray transient Cen X-4

We accurately determine the fundamental system parameters of the neutron star X-ray transient Cen X-4 solely using phase-resolved high-resolution UV-Visual Echelle Spectrograph spectroscopy. We first determine the radial-velocity curve of the secondary star and then model the shape of the phase-resolved absorption line profiles using an X-ray binary model. The model computes the exact rotationally broadened, phase-resolved spectrum and does not depend on assumptions about the rotation profile, limb-darkening coefficients and the effects of contamination from an accretion disc. We determine the secondary star-to-neutron star binary mass ratio to be 0.1755 ± 0.0025, which is an order of magnitude more accurate than previous estimates. We also constrain the inclination angle to be 32^{+8}_{-2} degrees. Combining these values with the results of the radial-velocity study gives a neutron star mass of 1.94^{+0.37}_{-0.85}M⊙ consistent with previous estimates. Finally, we perform the first Roche tomography reconstruction of the secondary star in an X-ray binary. The tomogram reveals surface inhomogeneities that are due to the presence of cool starspots. A large cool polar spot, similar to that seen in Doppler images of rapidly rotating isolated stars, is present on the Northern hemisphere of the K7 secondary star and we estimate that ~4 percent of the total surface area of the donor star is covered with spots.This evidence for starspots supports the idea that magnetic braking plays an important role in the evolution of low-mass X-ray binaries.

Integrated Earth Resistivity Tomography (ERT) and Multilevel Gas Sampling: A Tool to Map Geogenic and Anthropogenic Methane Accumulation on Brownfield Sites

Soil gas emissions of methane and carbon dioxide on brownfield sites are usually attributed to anthropogenic activities; however geogenic sources of soil gas are often not considered during site investigation and risk management strategies. This paper presents a field study at a redeveloped brownfield site on a flood plain to identify accumulations of methane biogas trapped in underlying sediments. The investigation is based on a multidisciplinary approach using direct multi-level sampling measurements and Earth resistivity tomography . Resistivity imaging was applied to evaluate the feasibility of identifying the size and spatial continuity of soil gas accumulations in anthropogenic and naturally occurring deposits. As a result, biogas accumulations are described within both anthropogenic deposits and pristine organic sediments. This result is important to identify the correct approaches to identify and manage risks associated with soil gas emissions on brownfield and pristine sites. The organic-rich sediments in Quaternary fluvial environments of São Paulo Basin in particular the Tietê River, biogas reservoirs can be generated and trapped beneath geogenic and anthropogenic layers, potentially requiring the management of brownfield developments across this region.

Optical coherence tomography for the diagnosis of neovascular age-related macular degeneration: a systematic review

The purpose is to study the diagnostic performance of optical coherence tomography (OCT) and alternative diagnostic tests for neovascular age-related macular degeneration (nAMD). Methods employed are as follows:systematic review and meta-analysis; Index test: OCT including time-domain (TD-OCT) and the most recently developed spectral domain (SD-OCT); comparator tests: visual acuity, clinical evaluation (slit lamp), Amsler chart, colour fundus photographs, infra-red reflectance, red-free images/blue reflectance, fundus autofluorescence imaging (FAF), indocyanine green angiography (ICGA), preferential hyperacuity perimetry (PHP), and microperimetry; reference standard: fundus fluorescein angiography. Databases searched included MEDLINE, MEDLINE In Process, EMBASE, Biosis, SCI, the Cochrane Library, DARE, MEDION, and HTA database. Last literature searches: March 2013. Risk of bias assessed using QUADAS-2. Meta-analysis models were fitted using hierarchical summary receiver operating characteristic (HSROC) curves. Twenty-two studies (2 abstracts and 20 articles) enrolling 2124 participants were identified, reporting TD-OCT (12 studies), SD-OCT (1 study), ICGA (8 studies), PHP (3 studies), Amsler grid, colour fundus photography and FAF (1 study each). Most studies were considered to have a high risk of bias in the patient selection (55%, 11/20), and flow and timing (40%, 8/20) domains. In a meta-analysis of TD-OCT studies, sensitivity and specificity (95% CI) were 88% (46–98%) and 78% (64–88%), respectively. There was insufficient information to undertake meta-analysis for other tests. TD-OCT is a sensitive test for detecting nAMD, although specificity was only moderate. Data on SD-OCT are sparse. Diagnosis of nAMD should not rely solely on OCT.

Roche tomography of cataclysmic variables - VI. Differential rotation of AE Aqr - not tidally locked!

We present Roche tomograms of the K4V secondary star in the cataclysmic variable AE Aqr, reconstructed from two data sets taken 9 d apart, and measure the differential rotation of the stellar surface. The tomograms show many large, cool starspots, including a large high-latitude spot and a prominent appendage down the trailing hemisphere. We find two distinct bands of spots around 22° and 43° latitude, and estimate a spot coverage of 15.4-17 per cent on the Northern hemisphere. Assuming a solar-like differential rotation law, the differential rotation of AE Aqr was measured using two different techniques. The first method yields an equator-pole lap time of 269 d and the second yields a lap time of 262 d. This shows that the star is not fully tidally locked, as was previously assumed for CVs, but has a co-rotation latitude of ˜40°. We discuss the implications that these observations have on stellar dynamo theory, as well as the impact that spot traversal across the L1 point may have on accretion rates in CVs as well as some of their other observed properties. The entropy landscape technique was applied to determine the system parameters of AE Aqr. For the two independent data sets, we find M1 = 1.20 and 1.17 M⊙, M2 = 0.81 and 0.78 M⊙, and orbital inclinations of 50° to 51° at optimal systemic velocities of γ = -64.7 and -62.9 km s-1.

Optical Coherence Tomography for the Monitoring of Neovascular Age-Related Macular Degeneration: A Systematic Review

Topic

To compare the accuracy of optical coherence tomography (OCT) with alternative tests for monitoring neovascular age-related macular degeneration (nAMD) and detecting disease activity among eyes previously treated for this condition.

Traditionally, fundus fluorescein angiography (FFA) has been considered the reference standard to detect nAMD activity, but FFA is costly and invasive. Replacement of FFA by OCT can be justified if there is a substantial agreement between tests.

Systematic review and meta-analysis. The index test was OCT. The comparator tests were visual acuity, clinical evaluation (slit lamp), Amsler chart, color fundus photographs, infrared reflectance, red-free images and blue reflectance, fundus autofluorescence imaging, indocyanine green angiography (ICGA), preferential hyperacuity perimetry, and microperimetry. We searched the following databases: MEDLINE, MEDLINE In-Process, EMBASE, Biosis, Science Citation Index, the Cochrane Library, Database of Abstracts of Reviews of Effects, MEDION, and the Health Technology Assessment database. The last literature search was conducted in March 2013. We used the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) to assess risk of bias.

We included 8 studies involving more than 400 participants. Seven reported the performance of OCT (3 time-domain [TD] OCT, 3 spectral-domain [SD] OCT, 1 both types) and 1 reported the performance of ICGA in the detection of nAMD activity. We did not find studies directly comparing tests in the same population. The pooled sensitivity and specificity of TD OCT and SD OCT for detecting active nAMD was 85% (95% confidence interval [CI], 72%–93%) and 48% (95% CI, 30%–67%), respectively. One study reported ICGA with sensitivity of 75.9% and specificity of 88.0% for the detection of active nAMD. Half of the studies were considered to have a high risk of bias.

There is substantial disagreement between OCT and FFA findings in detecting active disease in patients with nAMD who are being monitored. Both methods may be needed to monitor patients comprehensively with nAMD.

Optical coherence tomography for the diagnosis, monitoring and guiding of treatment for neovascular age-related macular degeneration:a systematic review and economic evaluation

BACKGROUND: Age-related macular degeneration is the most common cause of sight impairment in the UK. In neovascular age-related macular degeneration (nAMD), vision worsens rapidly (over weeks) due to abnormal blood vessels developing that leak fluid and blood at the macula.

OBJECTIVES: To determine the optimal role of optical coherence tomography (OCT) in diagnosing people newly presenting with suspected nAMD and monitoring those previously diagnosed with the disease.

DATA SOURCES: Databases searched: MEDLINE (1946 to March 2013), MEDLINE In-Process & Other Non-Indexed Citations (March 2013), EMBASE (1988 to March 2013), Biosciences Information Service (1995 to March 2013), Science Citation Index (1995 to March 2013), The Cochrane Library (Issue 2 2013), Database of Abstracts of Reviews of Effects (inception to March 2013), Medion (inception to March 2013), Health Technology Assessment database (inception to March 2013).

REVIEW METHODS: Types of studies: direct/indirect studies reporting diagnostic outcomes.

INDEX TEST: time domain optical coherence tomography (TD-OCT) or spectral domain optical coherence tomography (SD-OCT).

COMPARATORS: clinical evaluation, visual acuity, Amsler grid, colour fundus photographs, infrared reflectance, red-free images/blue reflectance, fundus autofluorescence imaging, indocyanine green angiography, preferential hyperacuity perimetry, microperimetry. Reference standard: fundus fluorescein angiography (FFA). Risk of bias was assessed using quality assessment of diagnostic accuracy studies, version 2. Meta-analysis models were fitted using hierarchical summary receiver operating characteristic curves. A Markov model was developed (65-year-old cohort, nAMD prevalence 70%), with nine strategies for diagnosis and/or monitoring, and cost-utility analysis conducted. NHS and Personal Social Services perspective was adopted. Costs (2011/12 prices) and quality-adjusted life-years (QALYs) were discounted (3.5%). Deterministic and probabilistic sensitivity analyses were performed.

RESULTS: In pooled estimates of diagnostic studies (all TD-OCT), sensitivity and specificity [95% confidence interval (CI)] was 88% (46% to 98%) and 78% (64% to 88%) respectively. For monitoring, the pooled sensitivity and specificity (95% CI) was 85% (72% to 93%) and 48% (30% to 67%) respectively. The FFA for diagnosis and nurse-technician-led monitoring strategy had the lowest cost (£39,769; QALYs 10.473) and dominated all others except FFA for diagnosis and ophthalmologist-led monitoring (£44,649; QALYs 10.575; incremental cost-effectiveness ratio £47,768). The least costly strategy had a 46.4% probability of being cost-effective at £30,000 willingness-to-pay threshold.

LIMITATIONS: Very few studies provided sufficient information for inclusion in meta-analyses. Only a few studies reported other tests; for some tests no studies were identified. The modelling was hampered by a lack of data on the diagnostic accuracy of strategies involving several tests.

CONCLUSIONS: Based on a small body of evidence of variable quality, OCT had high sensitivity and moderate specificity for diagnosis, and relatively high sensitivity but low specificity for monitoring. Strategies involving OCT alone for diagnosis and/or monitoring were unlikely to be cost-effective. Further research is required on (i) the performance of SD-OCT compared with FFA, especially for monitoring but also for diagnosis; (ii) the performance of strategies involving combinations/sequences of tests, for diagnosis and monitoring; (iii) the likelihood of active and inactive nAMD becoming inactive or active respectively; and (iv) assessment of treatment-associated utility weights (e.g. decrements), through a preference-based study.

STUDY REGISTRATION: This study is registered as PROSPERO CRD42012001930.

FUNDING: The National Institute for Health Research Health Technology Assessment programme.