text
string | predicted_class
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|---|---|---|
Time of admission was investigated as a potential influencing factor on the management of patients with chest pain. As hospitals have fewer staff at night, it was hypothesised that those admitted outside of normal working hours (17:30 - 08:00) would wait longer for clinical management and investigation. Further investigations sought to establish the effect of patient age on management decisions. Formal statistical testing was applied, with results as shown in Table 3.
|
study
| 99.94 |
This clinical review has identified several areas for discussion. Compliance with recent NICE standards was noted in establishing pain status and pain characteristics, eliciting previous episodes of chest pain, recording blood pressure, and completing a detailed physical examination. Furthermore, 99.2% of patients received an ECG during their presentation to the emergency department. It is likely that these measures would identify the vast majority of patients presenting with an acute coronary syndrome.
|
review
| 99.9 |
However, some areas for improvement were identified. Risk factor documentation was incomplete in a proportion of patients and a repeat ECG was frequently not undertaken. Aspirin was generally under prescribed and oxygen therapy was given outwith the recent guidelines. Trends involving time of admission, patient age and management decisions were also identified, and may require further exploration.
|
other
| 99.7 |
An ECG was recorded in the vast majority of patients in this cohort (99.2%). However, a single normal 12 lead resting ECG does not exclude a diagnosis of ACS, and NICE guidance recommends that all patients should have serial ECGs and continuous monitoring with telemetry when clinically appropriate. This study has found that only 59.3% of patients admitted with chest pain received more than one ECG, and only 57.6% were continuously monitored with telemetry. Serial ECGs improve the outcomes of patients later diagnosed with both ACS and MI, and their use is recommended in high risk patients .
|
study
| 86.9 |
It has been suggested that failure to repeat ECGs may lead to an increase in the number of missed cardiac diagnoses, however, there was no evidence this happened during the study. It is possible that the actual number of repeat ECGs was higher than found in this study, yet due to a combination of poor recording in the notes, and ECGs not being filed, the numbers appear lower.
|
study
| 99.94 |
The local policy on continuous telemetry suggests that those diagnosed with either AMI or unstable angina should be monitored, excluding those without a definitive diagnosis. On two occasions, telemetry was indicated but clinicians commented that it was unavailable. Unfortunately these comments are likely to be a true reflection of the financial constraints on the emergency department.
|
other
| 99.94 |
Aspirin is indicated in the initial management of patients with suspected cardiac chest pain. However in this cohort the use of aspirin appeared to be poor. Aspirin is frequently given en route by paramedic staff, and it is possible that this was not always documented. Furthermore, after discussion with staff members, it appears that some clinicians favour the prescription of clopidogrel over aspirin in the acute setting.
|
other
| 99.9 |
No systematic reviews or randomised controlled trials studying the use of aspirin versus clopidogrel in patients with acute current chest pain could be identified in the literature. NICE base their guidance on a cohort study assessing the efficacy of aspirin when given pre or post hospital admission. A lower mortality rate was found in patients that received aspirin pre admission compared to post admission at 7 days, (2.4% versus 7.3%, P = 0.002) , and this remained significant at 30 day follow up. Pre hospital aspirin reduced the risks of asystole (P < 0.001), resuscitation (P < 0.001) and ventilation (P < 0.002).
|
review
| 99.9 |
NICE recommend that other anti-platelet agents, such as clopidogrel, should only be given after patients have had an initial assessment which has refined the likely diagnosis, and they suggest that those diagnosed with AMI or ACS should be managed in line with other relevant guidelines .
|
other
| 99.9 |
Oxygen is indicated in patients with low oxygen saturations (< 94%) on air. Recent guidelines from NICE and the British Thoracic Society agree that supplementary oxygen has not been shown to be beneficial to these patients, and may indeed be harmful [5, 12]. In those with no risk of hypercapnic respiratory failure, the target saturation should be 94 - 98%, and in those who are at risk, a target of 88 - 92% is appropriate, until an arterial blood gas is available.
|
review
| 99.7 |
However, clinical practice has been slow to change in this regard and routine use of oxygen therapy persists despite these guidelines. The rate of oxygen prescription in those with normal saturations in this cohort was high, with 45.6% of individuals receiving oxygen inappropriately. Education of all members of staff may help to address this issue, improve patient care and allow resources to be allocated elsewhere.
|
other
| 99.9 |
Published research has shown that patients with myocardial infarction admitted to hospital overnight or at the weekend are managed less efficiently than daytime admissions [7, 13, 14]. This is of particular interest when time targets are established. This association may be a direct effect of staffing differences between day and night shifts.
|
study
| 99.1 |
In this current study the only significant correlation between time of admission and management was the use of the repeat ECG. Results show that patients admitted during the day were less likely to receive a repeat ECG than those admitted overnight (P = 0.032). It is possible that due to a larger number of general attendees to the emergency department during normal working hours, there is an increased demand for routine ECGs, and therefore admissions with chest pain were not monitored as often as they should be. However, it is also possible that repeat ECGs were performed, but were not recorded or filed within the medical record. Regardless, this would seem to imply that perhaps additional staffing is required during busy periods.
|
study
| 100.0 |
Whilst we have also found trends between patient age and aspirin prescription, these narrowly failed to reach significance. It is likely that this result is due to the small numbers available for statistical testing once stratified into age appropriate groups, and an adequately powered study is likely to have confirmed such a relationship. There is limited evidence to suggest that this lack of prescription is detrimental to patient care, and indeed this may be clinically appropriate decision making. As outcome data was not available within our study, this is unknown, however it would be interesting to explore this relationship in future work.
|
study
| 99.94 |
This was a retrospective audit, however the use of an audit data collection tool ensured that a complete dataset was obtained, and maintained consistency in recording data between patients. There was a low rate of exclusion within the study cohort, as only two of the original 120 identified were omitted from analysis. This improves the validity of the results.
|
study
| 99.94 |
In order to standardise the assessment and treatment of patients with acute chest pain, a new admission proforma has been implemented into the department. The current general admission document used within the emergency department does not contain a pre-written checklist section to be completed regarding risk factors, and this has also been updated.
|
other
| 99.94 |
As yet, there have been no published audit findings which discuss the uptake of new guidance on the management of recent onset chest pain, in particular the delivery of oxygen, and this paper highlights issues that still need to be addressed. As with all changes in medical practice, these guidelines will take time to become fully implemented. This early clinical review serves to raise awareness of the challenges which must be overcome in order to comply with new standards.
|
review
| 99.9 |
Despite good performance in a number of areas, this clinical review has highlighted that some standards are not being met in patients with chest pain. Clinicians must be aware of up to date guidance regarding oxygen therapy in chest pain, and aspirin should be used in all eligible patients when clinically appropriate. Serial ECGs must be used as a single 12 lead ECG does not exclude a diagnosis of acute coronary syndrome.
|
review
| 99.9 |
Hydrogen-bonded pigments are extremely stable, generally non-toxic materials which have recently found applications in organic electronics due to the observation of promising charge carrier mobilities in organic field-effect transistors (OFETs).1–6 Of the hydrogen-bonded pigments studied to date, epindolidione (EPI), a hydrogen-bonded derivative of the well-known organic semiconductor tetracene, is one of the most promising, with hole mobilities of up to 1.5 cm2 V–1 s–1 observed in thin film transistors.3 As for any molecular material, the physical properties are strongly influenced by the arrangement of the molecules in the solid state (i.e. the crystal structure).7 For charge transport in thin films, the molecular arrangement in the vicinity of the substrate is particularly important,8 and it has also been shown that new polymorphs, known as surface-mediated phases, can appear in this region.9 Structural characterization of thin films of materials to be used in organic electronic devices is therefore crucial to the understanding of their behavior.
|
study
| 80.6 |
In thin films of EPI, it was previously reported that the substrate temperature during film deposition can have a significant impact on the resultant transistor performance.5 The strong influence of preparation conditions on film structure is well known, and it was recently shown for another hydrogen-bonded pigment, Tyrian purple, that a new polymorph can be induced at low substrate temperatures.10 The performance variation in transistors produced from EPI deposited at different substrate temperatures points to structural differences in the thin films which are yet to be characterized.
|
study
| 100.0 |
EPI films also present an interesting example to study due to the fact that no crystal structure has been reported for this compound; attempts to grow single crystals suitable for structure solution have so far failed (though the crystal structures of two halogenated derivatives were solved).11 Such difficulties in the growth of high quality single crystals were also observed for the closely related quinacridone family of hydrogen-bonded pigments.12 The structural study of EPI thin films, therefore, presents an opportunity to attempt to solve the crystal structure directly from a thin film, for a material where, to date, no crystal structure has been forthcoming by any other means (such as single crystal X-ray diffraction or powder X-ray diffraction).
|
study
| 100.0 |
However, crystal structure solution from thin films is not a routine technique, and is normally only necessary when a surface-mediated polymorph is present for which single crystals cannot be grown.9 There are many difficulties associated with crystal structure solution from a thin film, primarily the indexation of diffraction patterns and the observation of a sufficient amount of data (often only a small number of Bragg peaks are observed). Extraction of reliable peak intensities, normally crucial for structure solution, is also challenging due to the strong influence of crystalline texture on the diffracted intensities.13–15 Recently, a method has been developed combining molecular dynamics (MD) simulations with grazing incidence X-ray diffraction (GIXD) data which only requires data sufficient to index and obtain a unit cell; this approach was recently used to solve the thin film structure of the hydrogen-bonded pigment Tyrian purple.10 A similar approach to the thin film crystal structure solution of EPI is taken here.
|
study
| 100.0 |
In this work, the growth of vapor deposited films of EPI and the solution of an elusive crystal is described; the impact of substrate temperature during deposition on film structure and morphology is also discussed. The results show the potential for a combination of X-ray diffraction and MD simulations to be used for crystal structure solution from thin films, when even only a very small number of diffraction peaks are observed. The importance of substrate temperature during deposition is highlighted by the observed differences in film structure and molecular orientation on the substrate. Film structure is then linked to the performance of transistors produced from films deposited in a similar manner.
|
study
| 100.0 |
Epindolidione (EPI) powder was synthesized following the procedure outlined by Jaffe and Matrick16 and taking account of the considerations of Kemp et al. 17 The powder was sublimation purified before use. EPI films of different thicknesses were deposited by physical vapor deposition onto 1 cm × 1 cm silicon substrates covered with a 150 nm thick layer of thermally grown oxide. Substrates were inserted into a vacuum chamber and cleaned by sputtering with Ar ions before being heated to ∼800 K to further remove contaminants. EPI was deposited from a Knudsen cell source in a vacuum with a base pressure of 2 × 10–8 mbar. Film thickness was monitored during deposition using a quartz microbalance where a conversion factor of Δ 1 Hz ≈ 0.083 nm was used.5 During deposition, the substrate temperature could be set to temperatures in the range of ∼120–800 K (cooling provided by liquid N2) and films were deposited at substrate temperatures of 200, 300, and 350 K. A detailed description of the experimental setup and sample mounting used is given elsewhere.18
|
study
| 100.0 |
Powder X-ray diffraction measurements on bulk EPI powder were performed on a Siemens D500 diffractometer in a Bragg–Brentano configuration. A Cu sealed tube (λ = 1.54 Å) was used, with the beam guided through a slit system before the sample; a secondary graphite monochromator was then used in front of a scintillation detector. The simulated powder diffraction pattern for the structure of EPI solved from the thin film was generated using the Mercury (CCDC) software package, which was also used for crystal structure visualization.19
|
study
| 99.94 |
Specular X-ray diffraction and X-ray reflectivity (XRR) measurements were made on a PANalytical EMPYREAN reflectometer using Cu Kα radiation (λ = 1.54 Å). On the primary side, a multilayer X-ray mirror was used to generate a parallel beam. On the secondary side, an anti-scatter slit and 0.02 rad Soller slit were used with a PANalytical PIXcel3D detector. Specular X-ray diffraction and XRR data are plotted as a function of q z, the out-of-plane component of the scattering vector, with q z = 4π/λ sin Θ, where λ is the X-ray wavelength and Θ is half of the scattering angle, 2Θ. XRR data were fitted and the electron density profile of films determined using the Stochfit software package.20
|
study
| 100.0 |
Grazing incidence X-ray diffraction (GIXD) experiments were performed at the KMC-2 beamline21 at the BESSY II synchrotron radiation source (Helmholtz Zentrum Berlin (HZB), Berlin, Germany) using an X-ray wavelength of 1.00 Å. A 2D VÅNTEC-2000 Mikrogap detector (BRUKER) equipped with an anti-air-scatter cone was used to record intensities. An incident angle of α i = 0.13°, close to the critical angle of the substrate, was chosen to enhance the scattered intensities and suppress scattering from the substrate. Reciprocal space maps were calculated from the measured data using the xrayutilities library for Python.22 Unit cell indexation and the calculation of structure factors was performed using the in-house developed software PyGID.23
|
study
| 100.0 |
Structure solution using the experimentally determined unit cell constants was performed using a combined molecular dynamics (MD) and density functional theory (DFT) approach. MD simulations were performed using LAMMPS in combination with the CHARMM General Force Field v. 2b7.24,25 Several thousand trial structures were generated by randomly placing one molecule into an expanded unit cell (120% the experimental unit cell volume). During the MD simulation run (70 ps with 1 fs time step), the system was allowed to relax while the unit cell shrunk back to the experimentally determined size. After equilibration at the experimental system size and a final energy minimization step, the atomic positions were extracted. Resultant structures were grouped based on their geometric similarity using the Hausdorff metric. In each structural grouping, characteristic features such as distinct hydrogen bond lengths or π–π interaction distances could be identified. Subsequently, to overcome the shortcomings of classical MD simulations, one representative structure from each group was used as an input for DFT geometry optimization as implemented in the VASP program (version 5.4.1).26–29 The PBE functional was used for exchange and correlation,30 with PAW potentials for all the elements.31 The effects of van der Waals interactions (vdW) were included using the pairwise method of Tkatchenko and Scheffler (TS).32 A plane-wave cutoff energy of 800 eV was employed. Calculations were performed on the primitive cell, containing 30 atoms, and a 3 × 2 × 1 Monkhorst–Pack k-grid to sample the Brillouin zone.33 The total energy during the self-consistency loop of each DFT step was converged to 10–8 eV. Calculations were performed using the experimental volume, relaxing atomic positions down to a threshold of 10–2 eV Å–1 on forces. The final optimized geometry was verified by calculating the phonon dispersion using density functional perturbation theory as implemented in VASP.
|
study
| 100.0 |
Hirshfeld surfaces34,35 and their corresponding fingerprint plots36 for EPI and derivatives were calculated using the Crystal Explorer37 software package. Hirshfeld surfaces offer a description of the electron density belonging to a defined unit (in this case molecules). Contrary to other types of molecular surfaces, Hirshfeld surfaces are defined by the molecule and the environment around it; the area enclosed within the surfaces presented here is defined as being where >50% of the electron density belongs to the selected molecule around which the surface is plotted. Two distances are defined for each point on the Hirshfeld isosurface: d e, the distance to the nearest nucleus outside the surface, and d i, the distance to the nearest nucleus within the surface. From these values, a normalized contact distance, d norm, can be defined relative to the van der Waals radii of the atoms involved, where d norm is either positive or negative depending on if the intermolecular contact distance is greater or less than the sum of the van der Waals radii.34 Plotting d norm on the Hirshfeld surface produces a surface with a red/blue/white color scheme; red areas correspond to contact distances shorter than the sum of the van der Waals radii, white areas approximately equal to the sum of the van der Waals radii, and blue areas where the distance is longer than the sum of the van der Waals radii (i.e. there are no close contacts). As plotting d norm on the Hirshfeld surface requires knowledge of the atom types associated with the values of d e and d i calculated at each point on the surface, it is possible to define the percentages of interactions to/from the surface arising from specific atom types. In this way, the Hirshfeld surface can be used to get information regarding types of intermolecular interactions occurring with a given molecule for which the surface is plotted.
|
study
| 100.0 |
AFM images were recorded for EPI films deposited at different substrate temperatures to observe any differences in the film morphology. Fig. 1 shows AFM images of nominally ∼100 nm thick films prepared at substrate temperatures of 200, 300 and 350 K. Unless otherwise stated, all results discussed below refer to samples with a thickness of 100 nm. All samples show fully covered substrates with a certain degree of roughness in the multi-domain films. The different substrate temperatures only induce minor differences in the film morphologies. For example, it can be seen that the films prepared at 300 and 350 K are smoother than those prepared at 200 K. Also, a small difference in the island/domain size is also noticeable, with the films prepared at 350 K having larger islands than those prepared at lower temperatures. The observed morphologies are consistent with previous morphological studies of EPI thin films.5
|
study
| 100.0 |
To better understand the molecular arrangement within the thin films, specular X-ray diffraction measurements (probing the periodicities normal to the substrate surface) were performed (Fig. 2). It is immediately apparent from the diffraction patterns that the different substrate temperatures have an impact on the film structure which is not reflected in the morphology, as assessed by AFM. In films prepared at 200 K, two broad, weak Bragg peaks are visible at ∼0.5 and 1.9 Å–1 which correspond to d-spacings of 12.45 and 3.29 Å, respectively. The first peak can be interpreted as standing molecules of EPI with a slight tilt of the long molecular axis away from the substrate normal (EPI has a molecular length of ∼12.6 Å).5 The second peak gives a d-spacing similar to the intermolecular distance of π–π interactions, suggesting that molecules lying parallel to the substrate surface are also present. The presence of molecules with two distinct orientations in the same film is not uncommon38–41 and the broad, weak nature of the diffraction peaks observed for films prepared at 200 K shows that the film is not well ordered.42 The fact that films produced at 200 K are mostly disordered can potentially explain, and is consistent with, the observed poor device performance of EPI transistors prepared at substrate temperatures of 200 K,5 as the degree of molecular ordering is strongly correlated with charge transport mobility in thin films.43
|
study
| 100.0 |
Films prepared at 300 K are much better ordered (seen from the increased intensity and sharpness of diffraction peaks) and several Bragg peaks are visible at 0.49, 0.57, 0.99 and 1.99 Å–1, which correspond to d-spacings of 12.66, 11.11, 6.34 and 3.15 Å, respectively. The peak at 0.49 Å–1 suggests a structure containing upright-standing molecules, similar to films prepared at 200 K, however now with a reduced tilt with respect to the surface normal; the peak at 0.99 Å–1 is the second order reflection of the same peak series. The subtle change in molecular tilt with respect to the structure observed in films prepared at 200 K suggests that there are potentially several polymorphs of EPI which differ primarily in the tilt of the long molecular axes (something previously observed for other rod-like molecules).9 The peak at 0.57 Å–1 suggests a second, more tilted polymorph of EPI is also present, with the peak having a reduced intensity compared with that of the other polymorph. The d-spacing of 11.02 Å to which it corresponds, again suggests molecules with an approximately upright-standing orientation, but now with an increased tilt away from the surface normal. This scenario is similar to the polymorphic behavior of the prototypical organic semiconductor pentacene, where several different polymorphs are known and can coexist within a thin film, each phase with a different out-of-plane d-spacing corresponding to a different molecular tilt.44 Therefore, the presence of multiple phases may suggest that a so-called surface-mediated phase9 is present in films of EPI. Finally, the comparably weak peak at 1.99 Å–1 shows that flat-lying molecules are again found to exist in the film, as this corresponds to the approximate length of a short intermolecular π–π interaction (3.15 Å).14 Overall, in EPI films prepared at 300 K, at least two (perhaps three) polymorphs are present with two distinct molecular orientations.
|
study
| 100.0 |
The third EPI film, prepared at a substrate temperature of 350 K, is also better ordered and has three Bragg peaks at 0.51, 1.01 and 2.02 Å–1, which correspond to d-spacings of 12.43, 6.22 and 3.11 Å, respectively. The first and most intense peak at 0.51 Å–1 again shows molecules in an approximately upright-standing orientation and appears to be the same phase which is present in films prepared at 200 K, and very similar, but not identical, to the phases present at 300 K; the second peak at 1.01 Å–1 is the second order reflection of the same peak series. The final peak at 2.02 Å–1 again suggests an approximately flat-lying molecular orientation and a coexistence of standing and lying domains. In all cases, films show defined textures with preferred orientations with respect to the substrate.
|
study
| 100.0 |
As different structures and domains are observed in relatively thick (∼100 nm) films, EPI films with an approximate thickness of 7 nm were investigated using X-ray reflectivity (XRR) measurements to observe if the structure is different in thinner films where the growth is not allowed to proceed. Such studies are of particular interest for the films prepared at 300 K, as it may allow the observation of which phase forms first and if there may be a thickness dependence for the different phases. The XRR data were fitted using a model-independent fitting routine20 to obtain an electron density profile of the film perpendicular to the substrate surface. Details on the morphology of ∼7 nm thick films by AFM are given in Fig. S1 of the ESI.†
|
study
| 100.0 |
The XRR curve and fit of the data for the sample prepared at 300 K are shown in Fig. 3(a). The data show the rapid decrease in intensity above the critical angle of the substrate (∼0.04 Å–1 in q z), typical for an XRR curve, followed by Kiessig fringes which give information on the thickness of the organic layer. Finally, at ∼0.47 Å–1 in q z, a Bragg peak can be observed which corresponds to the most intense Bragg peak observed in the specular X-ray diffraction measurements of the ∼100 nm thick sample (see Fig. 2). The fit of the data is shown superimposed over the experimental data in red in Fig. 3(a) and the electron density profile generated from the fit is shown in Fig. 3(b). The electron density profile shows regular oscillations which correspond to the periodic nature of the crystal packing perpendicular to the substrate surface, again, indicative of a well ordered film. The lower electron density of the first layer suggests that it is less ordered, and a better ordered film develops as subsequent layers are added. The decreasing electron density at higher z values (>60 Å) arises from the surface roughness of the film. The distance, d, determined from these oscillations gives a value of ∼12 Å for the thickness of one molecular layer. This again suggests approximately upright-standing molecules, though it is not clear which of the two standing phases observed in the specular X-ray diffraction data is present in the thinner films. The shape of the electron density plot for layers above the first layer suggests that the curve could be the result of a superposition of the electron density profiles for the two different phases; this would also explain the slightly irregular peak shapes (e.g. for the third layer, marked by an asterisk in Fig. 3(b)). The influence of the individual phases cannot be ascertained from the electron density plot, however, from the specular diffraction data of the thicker film (Fig. 2), the peak corresponding to the less tilted phase is more intense. The XRR curves of the films prepared at 200 and 350 K do not show the same degree of densely packed periodic ordering perpendicular to the substrate and have a more disordered structure (see Fig. S2 in the ESI†).
|
study
| 100.0 |
On determining the presence of several polymorphs and different orientations of EPI molecules in films by analyzing the out-of-plane order within the films, grazing incidence X-ray diffraction (GIXD) measurements were performed to gain insight into the in-plane ordering, which is inaccessible to specular X-ray diffraction measurements. Reciprocal space maps generated from GIXD data for the ∼100 nm thick samples prepared at different substrate temperatures are shown in Fig. 4. The maps show the in-plane scattering vector, q xy, plotted against the out-of-plane scattering vector, q z, and reveal several clear diffraction features for each of the samples.
|
study
| 100.0 |
Starting with the data for the sample prepared with a substrate temperature of 350 K (Fig. 4, bottom), three features are visible at q z positions of ∼0.5, 1.0 and 2.0 Å–1. These peak positions are in good agreement with the peaks observed in the specular diffraction data presented in Fig. 2 (peaks would intercept the q z axis at ∼0.51, 1.01 and 2.02 Å–1). These features extend along Debye–Scherrer rings (rings along a constant q value), showing that while there is a preferred orientation of the molecules on the surface, there is also mosaicity present and the texture is not highly defined. The first two stronger features at lower q correspond to approximately upright-standing molecules, while the weaker feature at ∼2.0 Å–1 corresponds to molecules lying on the substrate surface. A vertical feature resembling a rod smeared along a Debye–Scherrer ring is observed at q xy ≈ 1.88 Å–1, which corresponds to a d-spacing of 3.34 Å. This distance agrees well with the length typically associated with intermolecular π–π interactions and is in agreement with the observation of primarily standing molecules, as it is observed in the in-plane direction. The fact that no sharp Bragg peaks are observed, coupled with the presence of a rod-like feature in the in-plane direction points to a disordered layered structure: the film is partially ordered into layers perpendicular to the substrate surface, but there is no inter-layer ordering present as would be observed for a three-dimensionally ordered crystal.
|
study
| 100.0 |
For the sample prepared with a substrate temperature of 200 K (Fig. 4, top), the situation is markedly different. Here, only one strong peak is observed along the direction of the vertical axis at q z ≈ 1.9 Å–1. The peak also extends weakly along a Debye–Scherrer ring, again pointing to significant mosaicity in the film. However, the strength of this feature close to q xy = 0 shows that there is a strong preferred orientation, with a significant amount of lying molecules at the surface, as this peak corresponds to a d-spacing of 3.3 Å which can be related to intermolecular π–π interactions. The second significant feature is an in-plane peak at q xy ≈ 0.49 Å–1, which corresponds to a d-spacing of 12.9 Å, approximately the length of an EPI molecule. This feature confirms molecules lying with their long molecular axes parallel to substrate surface, and is in contrast to the situation observed in films prepared with a substrate temperature of 350 K, where molecules are mostly approximately upright-standing. The fact that the peak corresponding to the presence of lying molecule in the specular scan at q z = 1.9 Å–1 (Fig. 2) is not stronger when compared with the samples prepared at 300 and 350 K can be explained by the significant mosaicity of the 200 K film seen in the GIXD measurement (Fig. 4). This result shows that it is possible to tune the molecular orientation of the molecules on the surface only by changing the substrate temperature during deposition. The observed orientation of molecules in films prepared at a substrate temperature of 200 K also now clearly explains the observed poor performance of EPI transistors prepared in this manner,5 as charge transport through the film parallel to substrate is less favored due to the lying molecular orientation (i.e., perpendicular to the direction of the intermolecular π–π interactions). The absence of sharp Bragg peaks, and the presence of features resembling rods, again points to a disordered layered structure and highlights the poor order within the films, in agreement with the specular X-ray diffraction and XRR data.
|
study
| 100.0 |
The final sample, prepared at a substrate temperature of 300 K (Fig. 4, middle), again shows a different behavior. The peaks observed in the specular diffraction pattern (Fig. 2) are not observed here (regions close to q xy = 0 cannot be observed in GIXD reciprocal space maps), suggesting reduced film mosaicity (or a stronger preferred orientation) compared with the other samples. A strong rod-like feature is present at q xy ≈ 1.9 Å–1 (d = 3.3 Å), showing evidence of a disordered layer structure with molecules approximately upright-standing on the substrate surface, similar to the 350 K sample. However, in the case of the samples prepared at 300 K, Bragg peaks can also be observed at q xy values of ∼1.1 and 1.6 Å–1 and various q z. These Bragg peaks show that a three-dimensionally ordered species is also present with a preferred orientation on the substrate. Using the unit cell parameters from the previously determined structures of the 2,8-disubstituted chlorinated and fluorinated EPI derivatives (2F-EPI and 2Cl-EPI; CSD codes DUXYIG and DUXYOM, respectively)11 as a starting point (chemical structures are given in Fig. S3 of the ESI†), the Bragg peaks can be indexed and the unit cell parameters for EPI in thin films can be determined. The unit cell is given in Table 1, with EPI adopting a 001 orientation (the 001 lattice plane parallel to the substrate) in the 300 K thin film. This orientation of the unit cell means that EPI molecules are approximately upright-standing on the substrate surface, in agreement with the specular X-ray diffraction and XRR data.
|
study
| 100.0 |
The unit cell parameters determined from the 300 K film show a triclinic structure and are very similar to those determined for 2F-EPI, suggesting a similar type of packing motif. The volume of the unit cell means that only one EPI molecule is present in the unit cell (Z = 1). On the basis of this information, molecular dynamics (MD) simulations were performed to get information regarding the orientation of the molecule within the unit cell and to obtain a crystal structure solution for EPI in the 300 K thin films. Initial structures were generated by expanding the experimentally determined unit cell volume by 20% and randomly placing one molecule within the cell. MD simulation runs over 70 ps were performed, during which the unit cell was shrunk back to the experimentally determined dimensions while the systems relaxed. The resulting structures were first ordered based on energy, before several hundred of the lowest energy structures were grouped based on similarity according to certain criteria (e.g. Hausdorff distance to the lowest energy structure, π–π interaction distance, etc.). A representative structure from each group was then further optimized using dispersion corrected density functional theory (DFT) calculations. The simulated diffraction patterns of these structures were then compared to the experimental diffraction pattern and the final structure was chosen based on a comparison of the experimentally determined and simulated structure factors (Fig. 4, middle); this structure was also the lowest energy structure obtained from the DFT optimizations. Please note that the accuracy of this crystal structure is restricted based on experimental limitations (e.g. certain corrections to the peak intensities could not be applied due to the broad and weak nature of the observed Bragg peaks) and also the sample quality (only a small number of low intensity peaks are observed). However, the fact that a previously unknown crystal structure of a material can be determined from a thin film diffraction pattern based on a very limited dataset (∼7 Bragg peaks) is worth highlighting. The final structure determined from the thin film by the MD simulations and DFT optimization is shown in Fig. 5. The structure has a layered motif of molecules hydrogen-bonded to neighbors via two N–H···O hydrogen bonds, with N···O distances of 2.68 Å (Fig. 5, left), and intermolecular π–π interactions with neighboring molecules with a distance of 3.47 Å (Fig. 5, right). The hydrogen bond distance found in the structure is relatively short, but not uncommon.45 It should also be noted that this distance is likely strongly dependent on the choice of unit cell parameters; as there is only one molecule in the unit cell, it only self-interacts with molecules in adjacent unit cells.
|
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| 100.0 |
A final confirmation that the determined structure is plausible can be made by comparison with the known fluorinated and chlorinated derivative crystal structures (2F-EPI and 2Cl-EPI, respectively).11 A first visual comparison can be made by overlaying the conjugated backbone of a molecule in the EPI structure with those from the derivative structures and then generating the surrounding molecules of both structures to observe if there is an agreement in the extended crystal packing (see Fig. S4 in the ESI†). From this analysis, it can be seen that there is an excellent agreement between the packing in the EPI structure and that of the fluorinated derivative (2F-EPI), this is an encouraging indicator with regards to the chosen EPI structure. The similarity in the structures is perhaps unsurprising given the similar unit cell parameters (there is only a small reduction in volume of the EPI unit cell compared with the fluorinated derivative, most likely arising from the replacement of fluorine atoms with smaller hydrogen atoms). It should be noted here that the structures of the derivatives were not used as an input or reference at any point during the MD and DFT simulations, and were only studied once a final structure for EPI in the 300 K thin film had been chosen.
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A more quantitative comparison of the crystal structures and the intermolecular interactions taking place can be obtained using Hirshfeld surfaces and their corresponding fingerprint plots. An explanation of the generation of Hirshfeld surfaces is given in the experimental section and in the literature citations.34–36 Hirshfeld surfaces for EPI and the two halogenated derivatives, 2F-EPI and 2Cl-EPI, are shown in Fig. 6 mapped over a d norm range of –0.6 to 1.2 Å. The strongest intermolecular interactions between neighboring molecules, shown as the red areas on the Hirshfeld surfaces, occur for the N–H···O hydrogen bonds, blue areas correspond to areas with no close contacts (shorter than the sum of the van der Waals radii). Comparing the fingerprint plots of the different structures, again confirms the similarity of the EPI structure with that of 2F-EPI. The main difference between the fingerprint plot of the chlorinated derivative and those of the other structures is the presence of two wings, marked by asterisks in Fig. 6, at (d i, d e) positions of (1.8 Å, 1.2 Å) and (1.2 Å, 1.8 Å). These arise from C–H···Cl interactions, which are clearly absent in the other two structures. For the 2F-EPI structure, the analagous C–H···F interactions occur over similar (d i, d e) positions to the H···H interactions, showing that the addition of larger chlorine atoms to the conjugated backbone disrupts the packing of the hydrogenated EPI structure more than the addition of smaller fluorine atoms. A quantitative analysis of the contributions of different interactions to the Hirshfeld surface area shows that, for EPI and 2F-EPI, the H···H interactions are dominant, with contributions to the Hirshfeld surface area of 42.7% (EPI) and 20.5% (2F-EPI). For all three structures, contributions are also made by the O···H interactions arising from the hydrogen bonds (15.9% for EPI, 16.3% for 2F-EPI and 14.9% for 2Cl-EPI). In the case of 2Cl-EPI, the dominant interactions are Cl···H (23.6%), closely followed by H···H interactions (18.8%), while for 2F-EPI a significant contribution is also made by F···H interactions (18.8%). Generally, the Hirshfeld surfaces show the slight dominance of interactions involving the substituents to the conjugated backbone (involving H, F and Cl), as opposed to π interactions, C···C (mostly π–π) and C···H (mostly C–H···π) interactions (30.2% in EPI, 27.2% in 2F-EPI and 25.8% in 2Cl-EPI). A graphical representation of the relative contributions of different interactions to the Hirshfeld surfaces is given in the ESI† (Fig. S5).
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The final comparison which can be made is of the simulated powder diffraction pattern from the structure solved from the 300 K thin film with the experimentally determined powder diffraction pattern from the bulk powder used for the deposition of the films. As it is known that new polymorphs can form when a material crystallizes at a substrate surface, this is an important check to see if the structure obtained here is the bulk polymorph or a surface-mediated polymorph.9 The diffraction patterns of the bulk EPI powder and the simulated powder diffraction pattern of the structure solved from the thin film are shown in Fig. 7. There is a clear difference in the two powder diffraction patterns, suggesting that the structure solved from the thin film is actually a surface-mediated polymorph and not the bulk structure present in the powder. It should be noted, that it was not possible to index the diffraction pattern of the bulk EPI powder due to the significant anisotropic peak broadening caused by crystal defects and particle size effects (compare, for example, peaks shapes of the bulk powder with the calculated diffraction pattern of the thin film polymorph in Fig. 7). Therefore, from the data presented here, it is not possible to offer a crystal structure solution for the bulk EPI polymorph. As previously stated, it has been observed that growth of large, defect free crystals of EPI and the closely related family of quinacridone hydrogen-bonded pigments is challenging;11,12 this is also the likely reason that a crystal structure for EPI has not, until now, been solved. As no known bulk unit cell parameters are available, a direct comparison between the thin film diffraction pattern (see Fig. 4) and the bulk structure cannot be made. However, from visual comparison of the bulk EPI powder diffraction pattern and the simulated powder diffraction pattern of the structure solved from the thin film, it is clear that a different polymorph is present, adding a further level of complexity to the crystallization behavior of epindolidiones. The presence of a surface-mediated polymorph of EPI is significant, as it is likely this structure, and not the bulk polymorph, which dictates the properties of the high stability OFETs and organic light-emitting diodes (OLEDs) previously produced using this material.11
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| 100.0 |
In summary, thin films of EPI, with thicknesses of either ∼100 nm or ∼7 nm, deposited at three different substrate temperatures have been structurally characterized. While the film morphologies are relatively similar, different molecular orientations and tilts with respect to the substrate surface are found depending on the substrate temperature used during deposition; molecules are mostly approximately upright-standing in films prepared at 300 and 350 K, while films prepared at 200 K are mostly comprised of lying molecules. In the samples prepared at 300 K, where two approximately upright-standing phases are present, XRR measurements on very thin films (∼7 nm) could not distinguish which phase forms first during early film growth and it is suggested both phases grow at the same time. Films prepared with substrate temperatures of 200 and 350 K do not show a high degree of order, and are mainly comprised of disordered layered structures, with only out-of-plane order and very little in-plane order. An exception is observed for the film deposited at a substrate temperature of 300 K, where several Bragg peaks are observed in the GIXD data which could be indexed to provide a unit cell for EPI in the thin film. From this, the crystal structure in the thin film was solved using MD simulations and DFT optimization, followed by comparison of the structure factors of the most promising simulated structures with the experimental data. As the method does not rely on the evaluation of diffraction peak intensities (the crystal packing is derived from an energetic point of view), it allows for a crystal structure to be determined for systems where only a small number of weak, diffuse Bragg peaks are observed, such as in the case of EPI presented here. A crystal structure similar to the previously determined structure of the fluorinated EPI derivative was found.11 An assessment of the different interactions occurring within the crystal structures of EPI and the halogenated derivatives further emphasizes the similarity of the thin film structure to that of the fluorinated derivative, as opposed to the chlorinated derivative. Comparison of the simulated powder diffraction pattern from the crystal structure solved from the thin film with the diffraction pattern of the bulk EPI powder used for the deposition shows some clear differences, suggesting the structure found in the thin film is in fact a surface-mediated polymorph. It is therefore likely that this polymorph is responsible for the performance of some of the organic devices previously produced using this material,11 while the observation of lying molecules in films produced at 200 K explains the poor performance of OFETs produced from films deposited in such a way.5
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| 100.0 |
For advanced proximal gastric cancer (GC), the No. 10 lymph node (LN) is a crucial link in lymphatic drainage. Previous reports have found that the No. 10 LN metastasis rate is approximately 9.5% to 27.9% [1–3]. According to 14th edition of the Japanese gastric cancer treatment guidelines, D2 lymphadenectomy is the standard procedure for advanced GC, and the No. 10 LN should be dissected for the treatment of advanced upper GC. In recent years, as the concept of preserving viscera function and the use of minimally invasive technology has been accepted by an increasing number of clinicians, laparoscopic spleen-preserving splenic hilar LN dissection (SHLND) has become a valuable treatment option, and its use has gradually increased. In 2008, the South Korean scholar Hyung et al. reported the first use of laparoscopic treatment to preserve the spleen during SHLND of upper GC, achieving a good curative effect and indicating that the operation is safe and feasible. Since then, the use of laparoscopic surgery to preserve the spleen during SHLND has increased . However, this technology is difficult to implement in clinical practice because the spleen is deep, the operating space is narrow, and the splenic vessels are rich in this area and their branches are particularly complex. Thus, improvements in the preoperative prediction of No. 10 LN metastasis, which could provide medical evidence for SHLND indications, are urgently needed. However, few studies have focused on this topic. Therefore, we performed a retrospective study of patients subjected to laparoscopic spleen-preserving SHLND surgery to explore the preoperative factors associated with No. 10 LN metastasis and establish a new scoring system to preoperatively predict the risk of No. 10 LN metastasis.
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| 99.94 |
The 299 patients in the model development group included 228 males (76.5%) and 70 females (23.5%) with a mean age of 60.44 ± 10.29 years. The average body mass index (BMI) of the patients was 22.15 ± 2.71 kg/m2. The preoperative clinicopathological characteristics of the patients between the modeling and validation groups were compared, and the differences showed no statistical significance (Table 1).
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| 100.0 |
Table 2 summarizes the intraoperative and postoperative clinicopathological characteristics of the patients in the modeling group. The number of metastasizing LNs, blood loss volume (BLV) of splenic LNs and number of vascular clamps used for the splenic hilus and undifferentiated adenocarcinoma were significantly higher in patients with No. 10 LN metastasis than those in patients without No. 10 LN metastasis. A total of 44 (14.8%) patients showed postoperative complications. The general complications observed in patients with No. 10 LN metastasis were similar to those in patients without No. 10 LN metastasis (P = 0.447). However, abdominal chyle leakage in patients with No. 10 LN metastasis was significantly more prevalent than that in patients without No. 10 LN metastasis (P = 0.004) (Table 2).
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| 99.94 |
A total of 38 cases of No. 10 LN metastasis were identified in the model development group, yielding a transfer rate of 9.6. The median follow-up period was 33 (range, 18-66) months. The 3-year overall survival rate was 72.3%. The 3-year OS for patients with No. 10 LN metastasis was significantly shorter than that for patients without No. 10 LN metastasis (51.6% vs. 74.5%, P = 0.002) (Figure 1).
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| 100.0 |
Table 3 shows the results of the univariate and multivariate analyses of the potential risk factors for patients with No. 10 LN metastasis. Three factors were associated with an increased risk of No. 10 LN metastasis, including preoperative tumor size, preoperative T stage, and preoperative N stage (P < 0.003). The results of the multivariate analysis identified preoperative tumor size (P = 0.006), preoperative T stage (P = 0.001), and preoperative N stage (P = 0.029) as adverse risk factors for No. 10 LN metastasis. We divided the cases into 2 groups according to the tumor size (≥5 cm, <5 cm). The No. 10 LN metastasis rate for each subgroup is shown in Table 4.
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| 100.0 |
Despite differences in the regression coefficients, which ranged from 1.082 to 2.094 for No. 10 LN metastasis, for simplicity, 1 point was assigned for the preoperative T stage and preoperative N stage and 2 points were assigned for the tumor size. The resulting TNS (preoperative T stage, preoperative N stage, and tumor size) scores were obtained for No. 10 LN metastasis, and the patients in the modeling group were divided into three levels according to this scoring system: low risk (0-2 points, because the incidence rates of No. 10 LN metastasis among patients in 0 and 1 points was 0, 0-2 points were classified as low risk level), intermediate risk (3 points) and high risk (4 points). The distribution of patients according to the scoring system was 59.1% low risk; 26.5% intermediate risk; and 14.4% high risk. The incidence rates of No. 10 LN metastasis among patients in the low-, intermediate-, and high-risk categories were 2.8%, 13.9%, and 34.9%, respectively (χ2 = 28.60, P < 0.001). The relative risks of No. 10 LN metastasis in the intermediate- and high-risk groups compared with those of the low-risk group were 5.532 (95 %CI, 1.853-16.518, P = 0.002) and 18.321 (95 %CI, 6.171-54.392, P < 0.001), respectively (Table 5). The 3-year OS for patients in the low-risk category was significantly higher than that for patients in the intermediate- and high-risk groups (81.3% vs. 60.8% vs. 65.1%, P = 0.001) (Figure 2).
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| 100.0 |
The area under the ROC curve was 0.820 for the simplified TNS score for No. 10 LN metastasis. Compared with tumor size, preoperative N staging or the preoperative T staging, the TNS score more accurately predicts No.10 LN metastasis (Figure 3). The incidence rates observed in the validation set were compared to the predicted incidence rates to evaluate the model performance. The ratio of the expected to observed risk of No. 10 LN metastasis was 1.49, (χ2 = 0.84, P = 0.359), indicating good calibration. The ratios of the expected to observed risks for the low-, intermediate-, and high-risk categories in the validation set were 1.56, 1.08, and 2.09, respectively. There were no statistically significant differences among the groups (Table 6).
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| 100.0 |
GC is one of the most common malignant tumors of the digestive system. Individualized effective treatment must be developed to enhance the postoperative survival rate of GC patients. LN metastasis is an important factor decreasing the prognosis of patients with GC, and thorough LN dissection significantly influences the success or failure of the surgery. Currently, the D2 LN dissection technique is considered the standard operation for advanced GC. No. 10 LN dissection is critical, and difficulties in D2 radical advanced upper GC have been reported. According to previous studies, the No. 10 LN metastasis rate is approximately 9.5% to 27.9% [1–3]. The results of the present study showed that the incidence of No. 10 LN metastasis was 9.55 in upper GC. Chikara et al. reported that the 5-year OS of No. 10 LN metastasis-positive patients was significantly lower than that of No. 10 LN metastasis-negative patients (23.8% vs. 41.4%, P < 0.05), and these authors suggested that spleen regional LN metastasis has a significant effect on the prognosis of patients. Shin et al. showed that the 5-year OS of No. 10 LN metastasis-positive patients was significantly lower than that of No. 10 LN metastasis-negative patients (11.04% vs. 51.57%, P < 0.001). Therefore, the dis-section of the No. 10 LN is necessary in advanced upper GC; otherwise, the radical excision of the tumor will be decreased. The concept of laparoscopic spleen-preserving SHLND is becoming increasingly accepted with the increasing application of laparoscopic GC radical surgery and advancements in surgical instruments. However, whether all cases of advanced upper GC should be treated using this laparoscopic spleen-preserving SHLND technique has not yet been determined. Therefore, how to predict splenic hilar LN metastasis and characterize the indications for SHLND has become a topic of considerable interest in the research community. However, previous studies analyzing the risk factors for No. 10 LN metastasis were confined to postoperative-related factors and thus were not applicable for preoperative prediction. To our knowledge, the present study is the first preoperative retrospective study investigating the factors related to No. 10 LN metastasis in upper GC.
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| 99.9 |
Based on previous studies of splenic hilar LN metastasis, we established that No. 10 LN metastasis is depended on primary tumor size, depth of invasion, general classification, and tumor cell type. The No. 10 LN metastasis rate of upper GC is significantly higher than that of lower GC . In the present study, a multivariate analysis was used to examine preoperative tumor size, preoperative T stage, and preoperative N stage as adverse risk factors for No. 10 LN metastasis. An analysis of 219 patients who underwent SHLND showed that the depth of invasion was closely correlated with No. 10 LN metastasis . The likelihood of No. 10 LN metastasis in patients with advanced GC was increased in patients with tumors penetrating the subserosa or muscularis, with more than 7 macroscopic LN metastases. Koga et al. reported that No. 10 LN metastasis frequently appeared in Borrmann type IV cancer or when the primary tumor involved the serosa or entire stomach. We propose that with tumor development, the growth and invasion depth of the tumor continuously progresses, and eventually, the tumor penetrates through the muscle layer and infiltrates the placenta percreta layer because the serous layer contains an abundant capillary lymphatic network; thus, the incidence of No. 10 LN metastasis increases significantly. Moreover, GC patients with other LN metastases are closely related to No. 10 LN metastasis. The increased LN metastases and extensive transfer of the patients of preoperative staging of cN+, increases the probability of No. 10 LN metastasis. Due to the invasion of the metastatic LNs, the local anatomic structure is more complex, the intraoperative lymphadenectomy is more difficult and risky, thus more blood loss is caused by splenic vessel injury during surgery in patients with No. 10 LN metastasis than those in patients without No. 10 LN metastasis.Therefore, even if there is no difference in No. of retrieved No. 10 LNs between the two groups, patients with No. 10 LN metastasis revealed more blood loss and need more vascular clamps than those without No. 10 LN metastasis.
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| 99.94 |
According to the prediction for the risk of No. 10 LN metastasis, in a previous study, we demonstrated that prediction systems, including factors, such as the tumor infiltration depth and tumor transverse position, with No. 7 and No. 11 LN metastasis provide a better evaluation of No. 10 LN metastasis . However, the guidelines for the preoperative significance are not strong considering the postoperative parameters. This study constructed a TNS scoring system to predict No. 10 LN metastasis and classify patients into three categories: low, intermediate, and high risk. This scoring system identified a high-risk group, which has a 12.3-fold greater risk of No. 10 LN metastasis than the lowest-risk group, and this difference was statistically significant. Further analysis indicated that the area under the ROC curve was 0.820 for the simplified TNS score, with a discriminant ability similar to the logistic regression model, and in the validation group, there was no statistical significance between the observed and predicted incidence rates of No. 10 LN metastasis for the TNS scoring system. In the present study, we evaluated the related factors as preoperative readily available parameters for the simple and effective prediction of the risk of No. 10 LN metastasis and the preoperative discrimination of high-risk groups prone to transfer from low-risk groups, which has important significance for improving the prognosis of patients with upper GC by performing more corresponding, positive and effective targeted operation schemes. Therefore, in combination with the results of the present study, we propose that SHLND is not necessary for low-risk patients, whereas high-risk patients require regular treatments through SHLND. For patients with moderate risk, showing a 13.9% risk of No. 10 LN metastasis, we recommend SHLND to obtain a better radical cure effect (Figure 4).
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| 99.94 |
Some shortcomings of this study should be noted. These results were based on clinical data obtained from an eastern country at a single institution. Eastern countries have higher GC morbidity and more advanced-stage GC patients than western countries. Moreover, the average BMIs in eastern countries are lower than those in western countries. The results showed there is no significant difference in No. 10 LN metastasis between the patients with and without neoadjuvant chemotherapy, regardless of the modeling or validation group, which proving that the neoadjuvant chemotherapy didn't change the original status of No. 10 LNs. Therefore, a prospective multiple-center study with a large population would help validate this scoring system in a sample of patients from both eastern and western countries.
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| 100.0 |
This study presents a retrospective analysis of a prospectively collected database of upper- or middle-third GC patients treated with laparoscopic spleen-preserving SHLND in the Department of Gastric Surgery of Fujian Medical University Union Hospital, Fuzhou, China, between January 2011 and December 2014. The following inclusion criteria were used: (1) histologically confirmed primary adenocarcinoma in the upper- or middle-third stomach; (2) no evidence of tumor invasion in adjacent organs (pancreas, spleen, liver, or transverse colon), enlargement or integration of the para-aortic or splenic hilar LNs, or distant metastasis demonstrated by preoperative abdominal computed tomography (CT), abdominal ultrasound or endoscopic ultrasound; and (3) a total gastrectomy plus D2 lymphadenectomy with curative R0 resection based on the postoperative pathological diagnosis. The exclusion criteria were patients with T4b tumors; incomplete clinicopathological data; intraoperative evidence of peritoneal dissemination or distant metastasis; or gastric stump carcinoma. A total of 398 patients, including 302 males and 96 females with a mean age of 60.76 ± 10.58 years, were included in the present study. The preoperative size, location, T stage (with or without the presence of serosal invasion) and N stage (with or without LN metastasis) of the neoplasm were assessed in all patients via upper digestive endoscopy with biopsy, chest X-ray, total abdominal ultrasound, and abdominopelvic CT scan. Preoperative comorbidities were described according to the classification system of the American Society of Anesthesiologists . CT scans and multi-slice spiral CT angiography were performed to preoperatively assess the splenic vascular anatomy. BLV(mL) of splenic LNs was estimated according to the number of the gauze blocks and the trip attraction of aspirator, A piece of “two by two” is equivalent to 4 ml.The patient demographics, underlying diseases, clinicopathology, and preoperative and postoperative monitoring data were recorded in a clinical data system for GC surgery. The type of surgical resection and extent of LN dissection were selected according to the Japanese gastric cancer treatment guidelines . The resected specimens were histopathologically examined and staged according to the 7th edition of the UICC TNM classification . According to the reported references [9–11], data were randomly divided into two subsets using SPSS version 18.0 (SPSS, Chicago, IL, USA) to create a 75/25 split, with one subset used for model development and the other used for validation testing.
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| 99.94 |
Trained investigators performed the postoperative follow-ups through mailings, telephone calls, home visits or outpatient services. The majority of patients routinely underwent physical examinations, laboratory testing (including CA19-9, CA72-4, and CEA levels), chest radiography, abdominal US or CT, and an annual endoscopic examination. Overall survival (OS) was calculated from the day of surgery until death or until the final follow-up date of June 2016, whichever occurred first.
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study
| 99.9 |
The continuous data are reported as the means ± SD, and the differences between the groups were analyzed using t-tests. The categorical data are presented as the proportion and percentage, analyzed using the chi-square test or Fisher’s exact test. The variables in the models reaching P < 0.05 in the univariate analysis were subsequently included in a multivariate binary logistic regression model. The variables that remained significant in the multivariate analysis were used to construct a scoring system to classify patients into groups based on their risk for laparoscopic hemostasis. The results of the multivariate analyses are expressed as odds ratios (ORs) with corresponding 95% confidence intervals (95%CIs). A goodness-of-fit test was conducted to assess how well the model could discriminate between patients with and without No. 10 LN metastasis. Receiver operating characteristic (ROC) and area under the curve (AUC) analyses were used to determine the adequacy of the prediction models. Values of 0.7 and higher were considered clinically significant . The model calibration, or the degree to which the observed outcomes were similar to the outcomes predicted by the model across patients, was examined by comparing the observed averages with the predicted averages within each subgroup, arranged in increasing order of patient risk. Values of P < 0.05 were considered statistically significant. The statistical analyses were performed using SPSS version 18.0 (SPSS, Chicago, IL, USA).
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| 100.0 |
Scientific and technological advances continue to successfully exploit the fascinating properties of graphene, a class of materials with a two dimensional structure that possess an array of unique properties. It consists of single atom thick monolayers hexagonally arranged sp2 bonded carbon atoms forming a lattice, the thinnest known substance made from carbon, with a large specific surface area that is exceptionally strong and stiff with a high thermal and electrical conductivity. This two-dimensional sp2-hybridized carbon material itself is inert to many reactants and all graphene-bound anions reported to date possess major limitations in terms of their electronic tunability and coordination chemistry. However, graphene oxide (GO), a highly defective form of graphene with a disrupted sp2-bonding network, offers imperfect polar surfaces and secondary reactive sites capable of covalent and non-covalent chemical modification with organic and inorganic molecules . Research on graphene oxide specifically exploiting the high oxygen containing functional groups has seen new frontiers with promising applications as nanomaterials for analytical chemistry, heavy metal pollutant cleaning up agents[6–10], biotechnology, electronics, optics, energy storage, bio and chemical sensors and electronic nano-devices[12–14]. Tubular carbon nanomaterials such as carbon nanotubes (CNTs), discovered by Iijima, have also been in the research forefront in the last decade due to their excellent electrical properties with a superb conductivity, remarkable mechanical strength and modulus with many potential technological applications . However, newer materials such as Aerographite with micro and nano tubular network structures have been reported to exhibit very high surface area and large free volume with low density that are flexible and possess outstanding mechanical properties with enormous prospect in supercapacitors to electrocatalyst applications . Aerographite decorated by ZnO nanocrystallites have been reported that have promising applications in optoelectronic technologies, aerographite-GaN hybrid networks as possible next generation materials for electronic, photonic and sensors applications, and carbon nanowall (CNW) tetrapods coupled to nanocrystalline diamond in a 3D hybrid form as an excellent candidate for energy storage are other remarkable examples of advanced 3D carbon-based materials. Also very recently, introduction of ionic groups in the graphene lattice have been reported, exemplifying the first of an ionic graphene salt containing boron. These new materials consist of single functionalized graphene or GO sheets, which adhere together by van der Waals forces with residual π-π stacking between the faces of each sheet. 3D graphene oxide networks can also be synthesised by metal ion coordination chemistry, which has been shown to be an effective way of interconnecting or cross-linking carbon nanotubes (CNTs) , GO , or chemically modified graphene (CMG) with CNTs through the oxygen-containing functional groups via divalent cations (Ca2+, Mg2+, Cu2+ and Pb2+).
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review
| 99.9 |
GO can also be readily manipulated via chemical functionalization and has been utilized to develop highly conductive nanocomposite of polystyrene with uniformly dispersed graphene sheets. The hydrophilic functional groups present on the edges and basal planes of graphene oxide allow them to be readily exfoliated into monolayer sheets to yield stable suspensions in water. Since GO offers different wettability it enables interaction with biological molecules such as DNA, proteins via adsorption and or chemical bonding, which has prompted several biomedical applications. Various applications such as drug/gene delivery, reinforcing fillers in ternary composites to enhance properties of drug delivery carriers, photodyanamic therapy, functionalisation of GO for anti-cancer therapy and for siRNA delivery into neural stem cells to enhance neuronal differentiation have been reported. . Furthermore, the sharp irregular edges present in GO are being exploited for antibacterial activity and recent reports show that they are effective towards Gram positive bacteria . Graphene oxide inclusion in orthopaedic bone cements based on poly(methyl methacrylate) have also been reported to enhance mechanical properties, particularly the fracture toughness and fatigue properties and as additives or coatings leading to the next generation of metals for biomedical applications . Notably, graphene oxide is being explored in bone, cardiac, cartilage and neural tissue engineering applications. Composite formulations with poly(vinyl alcohol-chitosan and GO nanofibers were reported to enhance the mechanical properties with excellent biocompatibility and were deemed feasible as artificial cartilage , whilst a layer by layer assembly of cells within GO sheets were built to create a multi-layer functional tissue construct from cardiomyocytes and endothelial cells.
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review
| 99.9 |
The promising properties of GO with its flat two dimensional structure and the availability of functional groups with the potential of gelation and strong covalent interactions led us to explored the formation of 3D GO networks synthesised via crosslinking, using three different cations (Ca 2+, Zn2+ and Sr2+) at three different temperatures to expand the repertoire in biomedical applications. This approach will enable the inclusion of zinc and strontium in the matrix networks, which impart antibacterial properties to biomedical composites especially where surface contamination is a potential hazard. Additionally the presence of ions such as strontium and zinc are also known to accelerate bone healing and possess antibacterial properties, thus the incorporation of these ionic species within scaffolds for bone regeneration is of significance.
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study
| 100.0 |
Alginate is considered a very promising polysaccharide polymer that can be isolated from renewable sources such as brown algae or microorganisms. with applications in water treatment, an efficient alternative source for non-biodegradable plastic packaging materials and has many potential biotechnological applications since it is nontoxic, biocompatible, bioerodible and has a relatively low-cost in comparison with other polymeric materials. Sodium alginate can form hydrogels in the presence of divalent cations such as Ca2+ due to ionic cross-linking, owing to their chelation with the carboxyl groups. Crosslinked alginate chains form a buckled structure in the shape of an “egg box” whose cavity can accommodate divalent cations in the gelation process of water soluble sodium alginate. However, alginates possess poor mechanical properties, which restrict their widespread use in many biomedical and industrial applications. Hence, reinforcement of alginates via the incorporation of graphene oxide (GO) is promising with significant improvements reported using films of sodium alginate and fibers of calcium alginate . More recently, GO-alginate composite hydrogels synthesised by the direct mixing method using high amounts of calcium chloride have exhibited great enhancement of compression performance and water diffusion with the addition of even a minuscule amount of graphene oxide. This improvement of water diffusion is also very desirable in many biomedical applications due to mass transport plays an important role in cell survival .
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review
| 99.7 |
In this study, we hypothesize that using a facile and green route to create graphene oxides crosslinked with divalent cations such as calcium, zinc or strontium will yield three-dimensional GO networks that can be safely used for biomedical applications by virtue of the synthetic route and enable composite formulation with enhanced mechanical properties, which is exemplified through forming GO/calcium alginate composites in comparison to the use of single GO nanosheets and consequently also provide a simple process to include cations that enhance antibacterial effects and in trace amounts facilitate bone healing, thus can be explored for scaffolds for bone and wound healing applications.
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study
| 99.94 |
Graphene oxide was dispersed in distilled water and mixed with 10% (w/v in g/mL) calcium chloride with continuous stirring for 2 hours at 24, 34 and 55°C to obtain the GO networks coordinated by divalent calcium cations. The complex compounds synthesised were purified by centrifugation and washing twice with distilled water. The same reaction was performed using zinc chloride and strontium chloride to produce similar divalent complex compounds and these coordination compounds of crosslinked GO are hereafter referred to as cGO. The graphene oxide complexation compounds were subsequently vacuum dried at 60°C for 48 hours. This synthetic procedure was assessed by Raman spectroscopy and showed excellent stability and repeatability.
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study
| 100.0 |
The reinforced calcium alginate composites were synthesised by complexation reaction of calcium chloride (6 wt.%) and GO (1 wt. %) both dissolved in water under continuous stirring over 2 hours at 24°C, and subsequently mixing with a 2% (w/v in g/mL) aqueous solution of sodium alginate. The amount of each component were calculated to yield a composite composed of 6 wt.% of calcium chloride and 1 wt.% of GO both percentages are with respect to the mass of sodium alginate used in the preparation. Calcium alginate composites were also prepared with the same amount of graphene oxide and calcium cations but without following the complexation reaction to enable comparison. These composites are referred as cGO/Alg and GO/Alg respectively.
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study
| 100.0 |
Raman Spectroscopy was performed on a confocal micro-Raman spectrometer (Renishaw inVia) with an argon ion laser at an excitation wavelength of 633 nm from 1000 to 3000 cm-1. All scans were taken with x20 lens at 600 l mm-1 grating. Samples for Raman analysis were prepared by deposition of dry samples onto a glass substrate. Field Emission Scanning Electron Microscopy (FESEM, Zeiss Ultra 55 Model) with Energy-Disperse X-Ray Spectroscopy was operated at an accelerating voltage of 2 kV to observe the morphology of GO and the crosslinked GO networks at a magnification of 50000, and at 20 kV for the elemental analysis. High-resolution Transmission Electron Microscopy (HR-TEM) with Scanning Transmission Electron Microscope (STEM) Dark Field Imaging at a magnification of 300000 was performed using a JEOL-TEM 2100F 200 kV electron microscope dispersing the samples with dichloromethane in an ultrasonic bath for ten minutes and subsequent drying at room temperature. The micrographs of the calcium alginate composites were taken on a TSM Tandem scanning confocal microscope (TSM) (Noran Instruments, Middleton, WI, USA) with a Motorized Lab Jack (Thorlabs, LTD.,Ely, UK) in conjunction with an EMCCD camera iXon 885 EM-CCD (electron multiplying charge-coupled device) with iQ capture software (Andor Technology, Northern Ireland, UK). A Jade series differential scanning calorimeter was used to determine the thermal properties and Perkin Elmer Jade series software to process raw data. 10–20mg samples were carefully placed and sealed in aluminium pans (Perkin Elmer). The scans were carried out with reference pan calibrated using Indium49 under a Nitrogen7 atmosphere. The vacuum dried samples were subjected to a cooling scan from room temperature down to -30°C, followed by a heating scan up to 300°C at 10°C/min. These DSC scans were performed twice for each sample to ensure their reproducibility. A Perkin-Elmer DMA-800 dynamic mechanical analyser at a frequency of l Hz was used to determine the temperature dependence of storage modulus (E'), loss modulus (E”), and loss tangent (tan δ) from -50°C to 90°C of the dry samples with a heating rate of 1 K/min. FTIR transmission spectroscopy with a range of 650 to 4000 cm-1 was carried on a Perkin Elmer Spectrum One Fourier Transforms Infrared spectrometer.
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study
| 100.0 |
When divalent salts such as calcium chloride are dissociated in distilled water and agitated in an aqueous solution of GO, a complexation reaction occurs between the Ca2+ cations and the oxygen-containing functional groups, producing a continuous growing GO network due to the continuous bridging of the GO nanosheets by the divalent atoms tightly bonded by means of four oxygen atoms. Raman spectroscopy is frequently used to determine defects and ordered/disordered structures of graphene. The D band is recognized to be a disordered band originating in structural defects, edge effects and dangling sp2 carbon bonds that break the symmetry. The intensity ratio of the D band to the G band (ID/IG) is generally accepted as representative of the defect/disordered carbon structure. The effect of the reaction temperature and the type of divalent ions on the complexation reaction is shown in the Raman spectra (excitation with a 633 nm laser) in Fig 1A and 1B respectively. The GO complex networks synthesised show a very significant increase in the intensity of the D band with respect to that of GO. In addition, the ID/IG ratios of GO and cGO when crosslinked with Zn2+, Sr2+ and Ca2+ synthesised at 24°C are 0.96, 1.31, 1.25 and 1.11 respectively whilst the temperature of the reaction also had an effect and using calcium as the chelating agent the values were 1.17 and 1.26 at 34 and 55°C respectively. This clearly indicate an increase, demonstrating a significant level of disorder at the carbon edges due to the increase in defects and loss of symmetry arising due to the random bridging of the divalent atoms in the GO network. The intensity of these D-bands also decreases dramatically with increasing number of graphene layers, which indicates that crosslinking at the edges also occurs producing a 2D growth of the GO nanosheets interlinked by the divalent atoms. Thus, Fig 1 shows how the D-band intensity increases dramatically after the formation of the graphene oxide complexation networks and increasing temperature from 24 to 34°C indicate that the number of graphene layers decrease. The increase of the ID/IG ratios with increasing temperature, in spite of the broading of the G band due to the increase of the small D’ shoulder band, supports this last statement. This D’ shoulder appearing at around 1621 cm-1 in GO, related to the disorder of edge carbons, broadens on increasing the reaction temperature (Fig 1A) and when using different divalent salts (Fig 1B). This fact, once again, is in good agreement with the formation of complexation bonds at the edges. However, the D-band of Fig 1B shows that crosslinking of GO is much more effective using Zn2+ and Sr2+ at room temperature with ID/IG ratios, as mentioned, close to that obtained with Ca2+ at 55°C.
|
study
| 100.0 |
The FESEM micrograph with EDS analysis confirmed the presence of the divalent cations of Ca, Zn and Sr after the synthesis procedure with trace amounts (impurities) of chlorine atoms in all the coordination compounds (Fig 2). The EDS data shows that the weight percentage of oxygen atoms in GO and the GO coordinated networks are very similar.
|
study
| 100.0 |
Fig 3A shows that the GO powder used in this study is composed of unfolded GO nanosheets of approximately 100–200 nm in length forming aggregates stacked together mainly on its planar surface by van der Waals forces and π-π interactions. However, GO crosslinked with any divalent cation shows a very different structure of folded GO nanosheets (Fig 3B–3D) linked via divalent atoms. These images show very irregular morphology where the bridging of the GO sheets can be appreciated in the cGO samples in comparison with GO.
|
study
| 100.0 |
When these complex compounds are dispersed in dichloromethane in an ultrasonic bath for ten minutes, irregular micrometer length tubes of continuous crosslinked GO nanosheets can be easily separated and their structure can be very clearly observed by HR-TEM (Fig 4A and 4C). Besides, the lattice atoms of these continuous carbon materials crosslinked with divalent cations of Zn can be directly imaged (Fig 4B).
|
study
| 100.0 |
When crosslinked GO networks are employed to reinforce calcium alginate composites, the morphology of these samples are very different from that of calcium alginate composites prepared with uncrosslinked GO nanosheets (Fig 5). Thus, Fig 5A shows that most GO nanosheets are separated or form small aggregates around the alginate polymer matrix in comparison with the continuous crosslinked GO networks present in cGO/Alg, which can be clearly appreciated (Fig 5B, dark phase) by confocal microscopy in contrast to calcium alginate (light phase).Additionally, continuous irregular tubes of crosslinked GO with divalent calcium atoms can also be visualised in this confocal image forming sometimes right angles between them (see Fig 5D). However, there are three huge irregular micrometer-size continuous GO forms in GO/Alg, which indicate that GO crosslinking also occurs in GO/Alg during the gelation process.
|
study
| 100.0 |
When the reaction is conducted with cGO, a darker hydrogel is obtained. Similar to graphene, GO is highly transparent in the visible spectrum, the degree of transparency being attributed to electrostatic, chemical, van der Waals interactions and others that, remain largely unknown. However, the transparency of graphene oxide decreases as a function of its number of layers. Therefore, these new alginate composites are much darker because they have folded 3D GO networks instead of uncrosslinked GO sheets. In addition, cGO/Alg is much more consistent as observed by the differential scanning calorimetry (DSC) measurements that show a more homogeneous behaviour with less crystallisation peaks on heating starting at higher temperature (Fig 5C followed by a melting peak related to thermal degradation of the alginate at a higher temperature. Besides, its chemical structure seems to be much better linked after immersion in distilled water for 3 hours at room temperature (24±1°C) (Fig 5E). Hence, bonds between GO nanosheets and alginate chains occur via divalent calcium atoms in both GO/Alg and cGO/Alg. However, continuous crosslinked GO nanosheets linked to the alginate polymer matrix through these bonds produce a higher reinforcement as expected (Fig 6). In this Fig 6, the storage modulus (E′) and loss tangent (tan δ) are investigated by dynamic mechanical analysis (DMA) to determine the performance of these two composite materials under stress at various temperatures. For both samples, a decrease in storage modulus (E’) is observed as the temperature increases because the material undergoes a glass/rubber transition state. It is also noticed that the incorporation of crosslinked GO into the alginate matrix (sample cGO/Alg) leads to a considerable increase in the storage modulus (E’) as compared with the addition of single GO sheets (sample GO/Alg). The raise in the storage modulus is due to the higher reinforcing effect of the irregular graphene oxide tubes and higher interfacial interaction between these tubular carbon materials and alginate that restricts more the mobility of polymer chains at Alginate-cGO interface and high modulus of cGO. The damping factor (tan δ) exhibits a single dynamic mechanical relaxations in cGO/Alg in contrast to the heterogeneous behaviour of GO/Alg with two mechanical relaxations in good agreement with the DSC results.
|
study
| 100.0 |
The FTIR spectra show that the functional groups of GO/Alg and cGO/Alg are very similar as expected (Fig 7). Thus, a broad peak around 3250 cm−1 corresponds to OH stretching vibration, the bands at 1600 cm−1 and 1414 cm−1 correspond to symmetric and asymmetric COO− stretching vibration of carboxylate salt group, and the peak at 1030 cm−1 due to the stretching vibration of C−O−C groups respectively. The shoulder peak at 1087 cm−1 is attributed to the C−O stretching of sodium alginate. However, the intensity of the peak corresponding to the carbonyl esters (1735–1750 cm−1) increases considerably indicating that this group plays a more important role in cGO/Alg due to the GO crosslinking via divalent cations by coordination chemistry and a slight shift of this peak from 1750 to 1746 cm-1 is observed.
|
study
| 100.0 |
In literature, it has been reported that the addition of GO can enhance the storage modulus of alginate-based materials . However, to the best of our knowledge, there is not any publication on the enhancement of E’ for composite hydrogels synthesised with irregular graphene oxide tubes with respect to those with single GO sheets. Therefore, these results confirm our hypothesis of these irregular graphene oxide tubes as better reinforcement agents than single GO sheets in alginate. The possibility of including zinc and strontium in the polymer matrix, which impart antibacterial and healing properties, render these new advanced materials very promising in the biomedical field.
|
study
| 100.0 |
In conclusion, this study reports a new green and low-cost synthetic procedure that has been developed to join GO nanosheets to produce folded 3D crosslinked GO networks by coordination chemistry to form irregular micrometer length tubes. Crosslinking of GO is much more effective using Zn2+ and Sr2+ at room temperature (24°C) than with Ca2+, which requires the temperature to be raised to 34°C to achieve the same crosslinking density. The synthesis of the new calcium alginate composites reported in this study thus show an example of the potential use of these GO networks to reinforce other materials showing a very significant increase in the storage modulus and a more homogeneous structure. Of note, is that this synthetic process is in keeping with the principles of green chemistry and in good agreement with the sustainable non-hazardous synthetic routes with no demands on thermal or sonic energy consumption. These 3D networks of GO coordinated with divalent cations (Ca, Zn, Sr or others) will enable broadening of the field towards the synthesis of new continuous carbon materials and reinforced composites such as alginates with unique electric, thermal, oxidative, and chemical properties with very promising applications in fields of electronics, optics, energy, environmental science and biotechnology in the near future.
|
study
| 99.94 |
Optical coherence tomography (OCT) has become a valuable ancillary test in the diagnosis and management of chorioretinal disease1. It can be used to acquire high-resolution, cross-sectional, non-invasive and non-contact in vivo images and biometric indexes as well as quantify retinal thickness in different layers.
|
other
| 97.94 |
Spaide and colleagues developed the technique of enhanced depth imaging (EDI) OCT, which provides in vivo, high-resolution, optical and cross-sectional images of the choroid, including choroidal thickness and large choroidal vessels2, 3. The reliability and repeatability of the choroid images have been documented in eyes with and without ocular diseases and in patients of different races4, 5. Therefore, the EDI-OCT has been an emerging area of study in various ocular diseases involving the choroid, including central serous chorioretinopathy, acute primary angle closure, open-angle glaucoma, nanophthalmic eyes, etc.6–9.
|
review
| 99.9 |
Although the outer border of the retinal pigment epithelium (RPE) hyper-reflective band is clear for the measurement of the subfoveal choroidal thickness (SFCT), the sclerochoroidal interface is not always easy to distinguish4. In case of artifact, it is more difficult to determine the accurate choroidal thickness. We found a widespread artifact that easily blurred the sclerochoroidal interface in EDI-OCT in our clinical practice. But the artifact has never been reported before.
|
study
| 99.94 |
Among the 149 participants, 21 had acute primary angle closure glaucoma (APACG), 24 had primary angle closure suspect (PACS), 32 had chronic primary angle closure glaucoma (CPACG), 25 had primary open angle glaucoma (POAG), 25 had central serous chorioretinopathy (CSC) and 20 were control subjects (Table 1).Table 1Demographic features of study participants.APACG (n = 23)PACS (n = 24)CPACG (n = 32)POAG (n = 25)CSC (n = 25)Control (n = 20)Mean age, yrs57.25 ± 12.6056.22 ± 12.1856.45 ± 9.2455.08 ± 12.5440.12 ± 6.5764.20 ± 11.60Male sex, n (%)7 (30.43%)7 (29.17%)14 (60.87%)9 (36%)23 (92%)16 (64%)Diopter (D)0.32 ± 1.580.47 ± 1.73−0.41 ± 1.02−1.08 ± 1.700.045 ± 1.25−0.09 ± 0.93
|
study
| 100.0 |
The linear artifact was found in 122 cases (81.88%). All the detected linear artifact was located stably at a depth of 485 μm beneath the RPE. The subfoveal choroidal thickness measured with EDI-OCT was 325.43 ± 140.98 μm in these subjects (Table 2).Table 2Ophthalmologic data (mean ± SD) of study participants.APACGPACSCPACGPOAGCSCControlFrequency of artifact, n (%)12 (52%)18 (75%)23 (72%)24 (96%)25 (100%)25 (100%)Subfoveal choroidal thickness (μm)319.39 ± 134.96348.38 ± 145.15336.00 ± 115.03283.88 ± 91.36495.00 ± 113.82240.35 ± 106.32Depth of the artifact (μm)485485485485485485Height from ellipsoid zone to RPE/Bruch’s complex (μm)79.83 ± 6.4283.41 ± 6.0482.17 ± 5.9182.33 ± 5.1477.00 ± 7.0778.60 ± 4.54Height of the artifact (μm)61.50 ± 6.2664.61 ± 5.5664.13 ± 6.5063.46 ± 4.8562.00 ± 7.0762.25 ± 4.71Foveal retinal thickness (μm)213.35 ± 14.90213.25 ± 13.36214.72 ± 13.26217.68 ± 14.98485.84 ± 151.15208.85 ± 14.51
|
study
| 100.0 |
The linear artifact could be observed below, at the same level as or above the sclerochoroidal interface, which was shown in Fig. 1.Figure 1Example of a linear artifact line (small linear segment) below, at the same level as or above the sclerochoroidal interface (bidirectional arrow) in EDI-OCT images. (A) A female chronic primary angle closure glaucoma patient with a linear artifact line below the sclerochoroidal interface with a SFCT of 429 μm. (B) A control male subject in which the linear artifact was at the same level as the sclerochoroidal interface with a SFCT value of 485 μm. (C) A central serous chorioretinopathy patient with a linear artifact line above the sclerochoroidal interface with a SFCT of 573 μm. SFCT: subfoveal choroidal thickness.
|
clinical case
| 81.8 |
Example of a linear artifact line (small linear segment) below, at the same level as or above the sclerochoroidal interface (bidirectional arrow) in EDI-OCT images. (A) A female chronic primary angle closure glaucoma patient with a linear artifact line below the sclerochoroidal interface with a SFCT of 429 μm. (B) A control male subject in which the linear artifact was at the same level as the sclerochoroidal interface with a SFCT value of 485 μm. (C) A central serous chorioretinopathy patient with a linear artifact line above the sclerochoroidal interface with a SFCT of 573 μm. SFCT: subfoveal choroidal thickness.
|
clinical case
| 99.44 |
The distance between the inner and outer line of the linear artifact was 63.18 ± 5.52 μm, and the height from the ellipsoid zone to RPE/Bruch’s complex was 81.30 ± 5.65 μm. The linear artifact was like a miniature copy from the ellipsoid zone to the RPE/Bruch’s complex, and the reduction ratio was approximately 1:1.3 (Fig. 2). The rate of sclerochoroidal interface above, below or at the same level as the linear artifact line was 67.1%, 7.4% and 7.4%, respectively (Table 3).Figure 2The linear artifact and corresponding retinal structures in EDI-OCT. The ellipsoid zone, the outer segments of photoreceptors, the interdigitation zone and RPE/Bruch’s complex corresponded to the four zones of linear artifact, respectively. Table 3Rate of linear artifact line above, below or at the same level as the sclerochoroidal interface.APACGPACSCPACGPOAGCSCControlTotalBelow10 (43.5%)14 (58.3%)19 (59.4%)24 (96%)14 (56%)19 (95%)100 (67.1%)At the same level1 (4.3%)2 (8.3%)3 (9.4%)0 (%)4 (16%)1 (5%)11 (7.4%)Above1 (4.3%)2 (8.3%)1 (3.1%)0 (%)7 (28%)0 (0%)11 (7.4%)Not observed11 (47.8%)6 (25%)9 (28.1%)1 (4%)0 (0%)0 (0%)27 (18.1%)
|
study
| 100.0 |
The participants were divided into two groups according to their SFCT. SFCTs less than 300 μm were assigned to the normal SFCT group, while an SFCT equal to or greater than 300 μm was assigned to the thickened SFCT group. The rate of sclerochoroidal interface below and at the same level as the linear artifact line was only 2.2% in participants in the normal SFCT group, such as POAG patients and control subjects, but the rate was upto 20.1% in patients in the thickened SFCT group, such as APACG, PACS, CPACG and CSC patients. The difference between the two groups was statistically significant (p < 0.01).
|
study
| 100.0 |
To date, EDI-OCT has become a promising new method in clinical practice3. The changes to the choroid support the hypothesis that hemodynamic changes in the choroid may cause many ocular diseases. A thicker choroid is observed in central serous chorioretinopathy, primary angle closure, nanophthalmic eyes and uveitis compared with that in normal eyes. A thinner choroid is found in APAC-afflicted eyes with elevated IOP compared with that in eyes with normal IOP6, 7, 9–11. Choroidal thickness therefore was thought to be meaningful in the assessment of disease severity and in predicting prognosis. Tagawa et al. observed a thickened choroid prior to the recurrence of Vogt-Koyanagi-Harada disease11. SFCT increase might be an anatomic feature of angle-closure disease10, but not of open angle glaucoma12. In longer and more myopic young adult eyes, the SFCT is thinner13 and may be a useful prognostic modality in high myopia14. The significantly increased SFCT was observed throughout the 6-month follow-up after cataract surgery15. Shao et al. even found an association between thin SFCT and subcapsular cataract or cortical cataract16.
|
review
| 99.56 |
There is still some disagreement about the results and corresponding interpretation of SFCT in many circumstances. SFCT was found to be negatively correlated with age, and the SFCT in males was 18% higher than in females in some investigations17, 18. However, a different study demonstrated no significant correlation between SFCT and age and sex, nor was there a significant correlation with ethnicity19. Since EDI-OCT is a new technique and increasing attention has been paid to choroidal thickness, the accurate determination of the boarder of the choroid is crucial. Accurate determination of SFCT is composed of two aspects: one is the outer boarder of the RPE, which is always clear and easy to define, and the other is the outer boarder of the choroid, which is not so clear and is easy to be confused by factors such as the linear artifact.
|
study
| 93.94 |
The occurrence frequency of the linear artifact in the present study was 81.88%. In some cases of APACG, the transparency of refractive media was affected by factors such as corneal edema and glaucomatous fleck, resulting in poor image quality. In these cases, the linear artifact could not be observed. In cases with relatively clear refractive media, such as PACS, CPACG and POAG, the rates were higher. In cases with clear refractive media, such as CSC and in the control group, the rate was 100%. The linear artifact can also be detected in many published literatures on EDI OCT, although it has never been reported20–24. This demonstrated that the incidence of the linear artifact was high and that the visibility of the linear artifact was affected by the opacity of refractive media.
|
study
| 100.0 |
In the present study, the linear artifact was stably located at 485 μm from the outer border of the RPE hyper-reflective band in normal subjects and in subjects with many ocular diseases in which the SFCT is an important reference parameter. While the average SFCT in our study was 325.43 ± 140.98 μm, the actual sclerochoroidal interface could be located above, below or at the same level as the linear artifact. Because the location of the linear artifact line was stable, the different relative positions mainly depended on differing SFCTs. When SFCT was thin, the sclerochoroidal interface was located above the linear artifact, and the artifact had little influence over the measurement of SFCT. However, when SFCT was thick, the sclerochoroidal interface was located at the same level of the linear artifact, and interfered with the measurement of SFCT. When SFCT was thicker, the sclerochoroidal interface was located below the linear artifact. Therefore, the artifact is most likely to be mistaken for the sclerochoroidal interface in the absence of careful observation or a clear image, especially in eyes with a thickened choroid, such as in APACG, PACS, CPACG and CSC. The rate of sclerochoroidal interface below and at the same level as the linear artifact line was upto 20.1% in patients with increased SFCT. The results of this study show that the linear artifact is a confounding factor in assessing the thickness of the choroid, especially in patients with increased SFCT.
|
study
| 100.0 |
In clinical practice, it is not always easy to distinguish the outer choroidal margin on obtained images. The combination of variations in patients, refractive transparency, image quality and anatomy can all affect the determination of the sclerochoroidal interface, which affects the determination of choroidal thickness. A repeatability study of manual SFCT measurements conducted by Rahman et al. observed that a change of more than 32 μm was likely to exceed inter-observer variability in SFCT4. A previous investigation has shown relatively large SFCT measurement agreement in scans with a less visible choroidal outer boundary5. It illustrates the difficulty of locating the borderline of the choroid. To minimize the influence of the linear artifact, the following advice is recommended. First, capture images as clearly as possible. Second, evaluate images under the primary mode, that is, a white line on a black background. Finally, the average depth of the front interface of the linear artifact to the base of the RPE is 485 μm, and the linear artifact is similar to an amplified copy of the ellipsoid zone, the interdigitation zone and the RPE/Bruch’s complex. We hypothesized that this artifact is derived from a mirror mapping of the bands from ellipsoid zone to RPE/Bruch’s complex because the reflexes of the bands from ellipsoid zone to RPE/Bruch’s complex are strong and they are imaged again after secondary reflection by the lens. Caution should be paid to the interpretation of the choroidal thickness, especially when the choroidal thickness is approximately or exceeds 485 μm.
|
study
| 100.0 |
In conclusion, EDI-OCT imaging for SFCT measurement has recently emerged as a powerful adjunct to pathogenesis and prognosis and remains a research focus. However, a linear artifact is located stably at a depth of 485 μm beneath the retinal pigment epithelium in 81.88% of subjects which might confound the measurement of SFCT. Images must be assessed with care and awareness of the existence of linear artifacts when determining the sclerochoroidal interface, especially when it is approximately 485 μm.
|
study
| 99.94 |
This study was approved by the Human Ethics Committee of Zhongshan ophthalmic center, and informed consent was obtained from all participants in accordance with the Declaration of Helsinki. All experiments were performed in accordance with relevant guidelines and regulations.
|
other
| 99.94 |
This was a prospective, consecutive, investigator-masked, nonrandomized, cohort study and was performed at a single center (Fig. 3). Twenty healthy subjects and 129 patients were enrolled in this study. There were76 men and 73 women. The mean age of the participants was 55.44 ± 13.46 years (range, 24–78 years), and the best-corrected visual acuity was 20/20 to hand motions. Eligibility criteria were: 1) normal healthy subjects and 2) patients with APACG, PACS, CPACG, POAG and CSC. Exclusion criteria were: 1) Significant corneal or media opacity; 2) Diabetes; 3) Uncontrolled hypertension (systolic > 150 mmHg and diastolic > 90 mmHg); 4) Amblyopia; 5) Neurologic or systemic disease that could compromise vision; 6) medications that are known to affect retinal structure; 7) Physical and/or mental impairment; or 8) Inability to sign a consent form. None of them had history of high myopia, ocular trauma, or ocular surgery.Figure 3Summary and flow diagram of the study design (n: number of eyes). APACG: acute primary angle closure glaucoma; PACS: primary angle closure suspect; CPACG: chronic primary angle closure glaucoma; POAG: primary open angle glaucoma; CSC: central serous chorioretinopathy; SFCT: subfoveal choroidal thickness.
|
study
| 99.94 |
Summary and flow diagram of the study design (n: number of eyes). APACG: acute primary angle closure glaucoma; PACS: primary angle closure suspect; CPACG: chronic primary angle closure glaucoma; POAG: primary open angle glaucoma; CSC: central serous chorioretinopathy; SFCT: subfoveal choroidal thickness.
|
other
| 99.56 |
All participants were examined by two retinal specialists independently of each other. Two high-quality horizontal and vertical 9 mm EDI line scans across the fovea were obtained from each eye using the spectral-domain OCT device (wavelength: 870 nm; scan pattern: enhanced depth imaging; Spectralis; Heidelberg Engineering, Heidelberg, Germany). Eye motion artifacts were eliminated by a proprietary eye tracking device, and 100 frames of EDI OCT images were captured and automatically averaged to reduce speckle noise.
|
study
| 100.0 |
The SFCT was measured using the manual calipers of the proprietary device, was taken at the fovea, and was defined as the distance between the outer part of the hyper-reflective line corresponding to the base of the RPE and the hypo-reflective line or margin corresponding to the sclerochoroidal interface4. The SFCT values of the horizontal and the vertical scans were averaged for analysis. The depth of subfoveal linear artifact was measured from the base of the RPE to the upper end of the three hyper-reflective bands similar to the ellipsoid zone, the interdigitation zone and the RPE/Bruch’s complex. As demonstrated in Fig. 4, the thickness of the linear artifact was defined as the distance between the upper and the lower end of the three hyper-reflective bands. Each OCT figure was reviewed by at least two of the readers. The SFCT and the depth and the thickness of the linear artifact were measured by at least two experienced readers independently and the values were averaged to get the reported results if the difference in the measurements of the readers was within 15% of the mean of the values. In a few cases, there was disagreement in measurement, and the determination was referred to Dr. Liu, the senior author.Figure 4The linear artifact line measured by EDI-OCT. The height from the ellipsoid zone to RPE/Bruch’s complex and the depth and height of the linear artifact are demonstrated. RPE: retinal pigment epithelium.
|
study
| 100.0 |
Statistical analysis was performed using absolute frequency (n) and relative frequency (%) for the qualitative variables and the mean ± standard deviation for quantitative variables. T-test was used for comparing the differences of SFCT between control subjects and thickened SFCT group. A p value less than 0.05 was considered statistically significant. All statistical tests were performed using SPSS Statistical Software, Release 20 (Chicago, IL, USA).
|
study
| 99.94 |
Over the past 50 years, the World Bank has increasingly relied on resources contributed voluntarily from donors and held separately from its core budget to support projects and activities, particularly for global health.1 These resources are known as trust funds. In the case of the bank, these trust funds are synonymous with earmarked, extra-budgetary, and “multi-bi” aid (bilateral aid channelled through multilateral institutions).2 3 The absolute number and relative proportion of bank assets held in trust has skyrocketed since the early 1990s. In 2011, the bank was trustee to roughly half of the trust funds for official development assistance (ODA) worldwide,4 5 and in 2012-13 about 200 donors contributed $3.7bn to more than 1000 World Bank Group trust funds.6
|
other
| 99.94 |
The World Bank Group channels voluntary grants from donors in three major ways: through IBRD (International Bank for Reconstruction and Development) and IDA (International Development Association) trust funds, financial intermediary funds, and IFC (International Finance Corporation) trust funds. In this article we focus primarily on the World Bank’s IBRD and IDA trust funds and financial intermediary funds (table 1, see the first paper of this series for more on the World Bank Group’s structure).7 At IBRD/IDA, trust funds are classified as bank or recipient executed, depending on the bank’s management role. Bank executed trust funds are implemented directly by the bank.8 9 They typically fund technical support for IBRD/IDA country projects, provide seed funding for pilot projects, or contribute to the bank’s knowledge agenda. For recipient executed trust funds, the bank hands over implementation of the project to a third party, such as a country’s Ministry of Health or a non-governmental organisation.4 5 8 9 These trust funds generally co-finance IBRD/IDA lending operations, finance stand alone projects, or support debt servicing operations.8 9 Some recipient and bank executed trust funds share governance structures called “facilities,”4 10 which are designed to increase coordination. To reduce fragmentation and better recover costs from managing IBRD/IDA trust funds, the bank recently announced a policy to replace recipient executed trust funds with “hybrid funds,” which will have bank executed components.11
|
other
| 99.9 |
Financial intermediary funds are more flexible and complex financing mechanisms that—with rare exception—support global or regional partnerships. For this type of trust fund, the bank negotiates a customised agreement with implementing agencies, which generally makes the bank trustee of funds from multiple donors.4 9 12 In some cases, the bank’s role is restricted to holding, receiving, and transferring commitments on behalf of legally independent implementing agencies (for example, the Global Fund to Fight AIDS, Tuberculosis and Malaria), while in others the bank is both trustee of and major donor to the fund (for example, the African Programme for Onchocerciasis Control). Finally, IFC trust funds typically finance advisory services to businesses and governments, as part of its institutional mandate to promote private sector investment in developing countries. An example is the $1bn Health in Africa Initiative, which is designed to channel funds for private health facilities and healthcare delivery and has received donor support through small trust funds and a large private equity fund.13 14
|
other
| 99.9 |
Collectively, trust funds allow the bank to increase its income and role in global activities. At the end of 2016, the bank served as steward to about $11bn in trust fund resources at IBRD, IDA, and IFC, and held $23bn in financial intermediary funds.15 These resources finance a considerable proportion of the bank’s staff and operations, including over 60% of all global partnerships and nearly two thirds of the bank’s advisory and analytics work.15 16 In 2013, trust fund revenue was almost as substantial as that of the entire IDA.16
|
other
| 99.94 |
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