Molecular simulation of linear octacosane via a CG10 coarse grain scheme.

Following our previous work on the united-atom simulation on octacosane (C28H58) (Dai et al., Phys. Chem. Chem. Phys., 2021, 23, 21262-21271), we developed a coarse grain scheme (CG10), which is able to reproduce the pivotal phase characteristics of octacosane with highly improved computational efficiency. The CG10 octacosane chain was composed of 10 consecutive beads, maintaining the fundamental zigzag chain morphology. When the potential functions were set up and the coefficients were parameterized, our CG10 models yielded solid phase diagrams and transitions during an annealing process. We also detected the melting point by various means: direct observation, bond order, density tracking, and an enthalpy plot. Furthermore, our CG10 successfully reproduced the liquid density with only 2% underestimation, indicating its applicability across the solid and liquid phases. Therefore, with the ability to reproduce critical structure and property characteristics, our CG10 scheme provides an effective means of numerically modelling octacosane with highly improved computational efficiency.

Molecular dynamics simulation of octacosane for phase diagrams and properties via the united-atom scheme.

We used the united-atom scheme to build three types of crystalline structures for octacosane (C28H58) and carried out molecular dynamics simulations to investigate their phase properties. By gradually heating the three polymorphs, we managed to reproduce the sequence of experimentally reported crystalline phases and rotator phases. By studying the system density, molecule morphology, chain tilt angle and cell anisotropy, we hypothesized three mechanisms behind the observed system deformations and phase transformations during the annealing process. Furthermore, our model successfully predicted the melting temperature and heat of fusion. We also reproduced the characteristics of the rotator phases and the liquid phase, validating the transferability of the united-atom scheme among the different condensed phases of octacosane. Our methodology represents an effective and efficient means of numerical study for octacosane and may be used for other members of the n-alkane family.

Cardiopulmonary resuscitation-from the patient's perspective.

With increasing emphasis on patient autonomy, patients are encouraged to be more involved in end-of-life issues, including the use of extraordinary efforts to prolong their lives. Being able to make anticipatory decisions is seen to promote autonomy, empower patients and optimise patient care. To facilitate shared decision-making, patients need to have a clear and accurate understanding of cardiopulmonary resuscitation (CPR). This study aims to understand the knowledge and perspectives of the local community regarding resuscitation options and end-of-life decision-making and to explore ways to improve the quality of end-of-life discussions. An interviewer-administered survey was conducted with a prospectively recruited group of surgical patients admitted postoperatively to the day surgery ward of a single tertiary institution in Singapore from April to May 2015. The survey, modelled after two validated questionnaires, measured patients' knowledge, attitudes and preferences regarding CPR in a series of 18 questions. Fifty-one out of 67 (76.1%) patients completed the survey. Results indicated that 80.4% (n=41) of participants correctly understood the purpose of CPR, but 64.7% (n=33) did not know of any possible complications of CPR. Less than half (n=21, 41.2%) of participants had thought about life support measures they wanted for themselves. Most of the participants agreed that they should personally be involved in making end-of-life decisions (n=44, 86.3%). Many patients had a poor knowledge of CPR and other resuscitation measures and the majority overestimated the success rate of CPR. However, a majority were receptive to improving their knowledge and keen to discuss end-of-life issues with physicians.

Recall of discharge advice given to patients with minor head injury presenting to a Singapore emergency department.

INTRODUCTION: Most patients presenting to the emergency department (ED) with minor head injury (HI) can be discharged, provided a caregiver is present and careful discharge instructions are given. The study ED uses an advice leaflet with verbal reinforcement to patients and caregivers detailing post-discharge instructions and warning symptoms of worsening HI. We aim to evaluate local patients' and caregivers' compliance to discharge instructions and their ability to recall HI advice. METHODS: A prospective study was conducted in an adult ED between April 10, 2006 and May 1, 2006. All patients with minor HI discharged from the ED or its 24-hour observation ward were included in the study. A telephone survey was conducted within 48 hours of discharge using a standardised questionnaire. RESULTS: During the study period, 292 patients had HI, of which 182 were eligible for the study. 71 were uncontactable and one refused to participate, leaving 110 patients in the study. Patients' age ranged between 7 and 109 years (median 41 years). 100 confirmed receiving HI advice (57 percent received by patients, 26 percent caregivers, 16 percent both patients and caregivers). 29 percent of respondents reported non-compliance to discharge advice. Mean HI-symptom recall score was 1.9 (SD 1.6) (total 9 symptoms). 30 percent cited other symptoms not part of the HI advice, which they believed necessitated a return to the ED. Recall scores were not statistically different, regardless of mode of instruction (verbal or printed) or the recipient (patient, caregiver or both). CONCLUSION: Our study raises concerns about the reliability of discharge advice for minor HI patients.

Non-rigid image registration using a median-filtered coarse-to-fine displacement field and a symmetric correlation ratio.

Conventional approaches to image registration are generally limited to image-wide rigid transformations. However, the body and its internal organs are non-rigid structures that change shape due to changes in the body's posture during image acquisition, and due to normal, pathological and treatment-related variations. Inter-subject matching also constitutes a non-rigid registration problem. In this paper, we present a fully automated non-rigid image registration method that maximizes a local voxel-based similarity metric. Overlapping image blocks are defined on a 3D grid. The transformation vector field representing image deformation is found by translating each block so as to maximize the local similarity measure. The resulting sparsely sampled vector field is median filtered and interpolated by a Gaussian function to ensure a locally smooth transformation. A hierarchical strategy is adopted to progressively establish local registration associated with image structures at diminishing scale. Simulation studies were carried out to evaluate the proposed algorithm and to determine the robustness of various voxel-based cost functions. Mutual information, normalized mutual information, correlation ratio (CR) and a new symmetric version of CR were evaluated and compared. A T1-weighted magnetic resonance (MR) image was used to test intra-modality registration. Proton density and T2-weighted MR images of the same subject were used to evaluate inter-modality registration. The proposed algorithm was tested on the 2D MR images distorted by known deformations and 3D images simulating inter-subject distortions. We studied the robustness of cost functions with respect to image sampling. Results indicate that the symmetric CR gives comparable registration to mutual information in intra- and inter-modality tasks at full sampling and is superior to mutual information in registering sparsely sampled images.

Choice of collimator for cardiac SPET when resolution compensation is included in iterative reconstruction.

In clinical cardiac single-photon emission tomography (SPET) studies, collimators of different spatial resolution and geometric efficiency are available for imaging. In selecting the appropriate collimator for clinical use, there is a trade-off between spatial resolution, which can limit the contrast of the reconstructed image, and detection efficiency, which determines the noise in the image. Our objective was to assess which collimator is best suited for cardiac SPET when reconstruction is performed with and without compensation for distance-dependent resolution (CDR). The dynamic MCAT thorax phantom was used to simulate 180 degree technetium-99m cardiac data, acquired using either a general-purpose (GP) or high-resolution (HR) collimator. For GP and HR, the resolution at 15 cm was 11.5 mm and 9.5 mm respectively, and the corresponding relative efficiency was 1.0 and 0.52 respectively. Distance-dependent resolution, attenuation and noise were included in the projection data; scatter was not included. Ordered subsets expectation maximisation reconstruction (subset size 4) was performed with and without CDR. Results were evaluated by comparing the myocardial recovery coefficient and contrast between myocardium and ventricle relative to the original phantom, each plotted for different noise levels corresponding to increasing iteration number. The study demonstrated that, without CDR, HR gave the best results. However, for any given noise level with CDR, GP gave superior recovery and contrast. These findings were confirmed in a physical phantom study. Results suggest that improved reconstruction can be achieved using a GP collimator in combination with resolution compensation.

Improved efficiency for MRI-SPET registration based on mutual information.

Mutual information has been proposed as a criterion for image registration. The criterion is calculated from a two-dimensional grey-scale histogram of the image pair being registered. In this paper we study how sparse sampling can be used to increase speed performance using the registration algorithm of Maes et al. (IEEE Trans Med Imaging 1997; 16: 187-198) with a focus on registration of MRI-SPET brain images. In particular we investigate how sparse sampling and parameters such as the number of bins used for the grey-scale histograms and smoothing of the data prior to registration affect accuracy and robustness of the registration. The method was validated using both simulated and human data. Our results show that sparse sampling introduced local maxima into the mutual information similarity function when the number of bins used for the histograms was large. To speed up registration while retaining robustness, smoothing of the data prior to registration was used and a coarse to fine subsampling protocol, where the number of bins in the histograms were dependent on the subsampling factor, was employed, For the simulated data, the method was able to recover known transformations with an accuracy of about 1 mm. Using the human data, there were no significant differences in the recovered transformation parameters when the suggested subsampling scheme was used compared with when no subsampling was used, but there was a more than tenfold increase in speed. Our results show that, with the appropriate choice of parameters, the method can accurately register MRI-SPET brain images even when very efficient sampling protocols are used.

Application of distance-dependent resolution compensation and post-reconstruction filtering for myocardial SPECT.

Compensation for distance-dependent resolution can be directly incorporated in maximum likelihood reconstruction. Our objective was to examine the effectiveness of this compensation using either the standard expectation maximization (EM) algorithm or an accelerated algorithm based on use of ordered subsets (OSEM). We also investigated the application of post-reconstruction filtering in combination with resolution compensation. Using the MCAT phantom, projections were simulated for 360 degrees data, including attenuation and distance-dependent resolution. Projection data were reconstructed using conventional EM and OSEM with subset size 2 and 4, with/without 3D compensation for detector response (CDR). Also post-reconstruction filtering (PRF) was performed using a 3D Butterworth filter of order 5 with various cutoff frequencies (0.2-1.2 cycles cm(-1)). Image quality and reconstruction accuracy were improved when CDR was included. Image noise was lower with CDR for a given iteration number. PRF with cutoff frequency greater than 0.6 cycles cm(-1) improved noise with no reduction in recovery coefficient for myocardium but the effect was less when CDR was incorporated in the reconstruction. CDR alone provided better results than use of PRF without CDR. Results suggest that using CDR without PRF, and stopping at a small number of iterations, may provide sufficiently good results for myocardial SPECT. Similar behaviour was demonstrated for OSEM.

Impaired permeability in radiation-induced lung injury detected by technetium-99m-DTPA lung clearance.

UNLABELLED: This study evaluates the use of the 99mTc-DTPA aerosol lung clearance method to investigate radiation-induced lung changes in eight patients undergoing radiotherapy for lung or breast carcinoma. The sensitivity of the method was compared with chest radiography for detecting radiation-induced changes in the lung, regional alterations within (irradiated region) and outside (shielded region) the treatment ports, effect of irradiated lung volume, and dependence on time after radiotherapy. METHODS: Serial DTPA lung clearance studies were performed before the first radiation treatment (baseline), then weekly during a 5- to 7-wk course, and up to 12 times post-therapy over periods of 56-574 days. The total activity deposited in the lungs for each study was approximately 150 microCi (approximately 5.6 MBq). DTPA clearance, expressed in terms of the biological half-time, t 1/2, was computed from the slopes of the least-squares fit regression lines of the time-activity curves for the first 10 min for irradiated and shielded lung regions. RESULTS: Major findings include: (a) significant and early DTPA t 1/2 changes were observed in all patients during and after radiotherapy; (b) changes in DTPA t 1/2 values were observed in both irradiated and shielded lung regions in all patients suggesting a radiation-induced systemic reaction; (c) changes in DTPA t 1/2 values were correlated (p < 0.05) with the irradiated lung volumes; (d) significantly reduced DTPA t 1/2 values were observed in three patients who subsequently presented with clinical symptoms and/or radiographic changes consistent with radiation pneumonitis (t1/2 felt to 19% +/- 6% of baseline values, compared with 64% +/- 17% in the remaining patients [p < 0.01]); (e) the onset of decreased DTPA t 1/2 values in these three patients occurred 35-84 days before clinical symptoms and/or radiographic changes; and (f) DTPA t 1/2 tended to approach baseline values with time after radiotherapy, suggesting a long-term recovery in lung injury. CONCLUSION: These observations show significant and early alterations in DTPA lung clearance during and after radiotherapy that may provide a sensitive assay to monitor changes in radiation-induced lung injury and may facilitate early therapeutic intervention.

Glucose metabolic changes in nontumoral brain tissue of patients with brain tumor following radiotherapy: a preliminary study.

PURPOSE: Our goal was to measure the effect of radiotherapy on the brain glucose metabolism of tumoral and nontumoral tissue of patients with brain malignancies. METHOD: Fifteen patients with primary or metastatic brain tumors were studied with 2-deoxy-2-[18F]fluoro-D-glucose and PET prior to radiotherapy, and nine of them were rescanned 1 week after completing radiotherapy. RESULTS: Brain metabolism in patients (all brain regions except for tumoral and edematous tissue) was lower than that of matched controls (34.0 +/- 8.3 vs. 46.5 +/- 6.4 mumol/100 g/min; p < or = 0.0001). Five of the nine patients retested after radiotherapy showed decrements in tumor metabolism (47 +/- 10%; p < or = 0.05) and increases in brain metabolism (10 +/- 4%; p < or = 0.004), and the other four showed no changes in tumor or in brain metabolism. Radiotherapy-induced changes in tumor metabolism were negatively correlated with changes in brain metabolism (r = 0.85, p < or = 0.004), but not with changes in tumor volume (assessed with MR images). CONCLUSION: The study indicates that radiotherapy-induced increases in metabolism of nontumoral tissue are secondary to decreased tumor metabolic activity and not just due to volume reduction.

Effects of adenosine diphosphate on Ca2+ fluxes and Ca2+ accumulation of sarcoplasmic reticulum.

Ca2+ transport by sarcoplasmic reticulum vesicles was examined by incubating sarcoplasmic reticulum vesicles (0.15 mg/ml) at 37 degrees C in, either normal medium that contained 0.15 M sucrose, 0.1 M KCl, 60 microM CaCl2, 2.5 mM ATP and 30 mM Tes at pH 6.8, or a modified medium for elimination of ADP formed from ATP hydrolysis by including, in addition, 3.6 mM phosphocreatine and 33 U/ml of creatine phosphokinase. In normal medium, Ca2+ uptake of sarcoplasmic reticulum vesicles reached a plateau of about 100 nmol/mg. In modified medium, after this phase of Ca2+ uptake, a second phase of Ca2+ accumulation was initiated and reached a plateau of about 300 nmol/mg. The second phase of Ca2+ accumulation was accompanied by phosphate uptake and could be inhibited by ADP. Since, under these experimental conditions, there was no significant difference of the rates of ATP hydrolysis in normal medium and modified medium, extra Ca2+ uptake in modified medium but not in normal medium could not be explained by different phosphate accumulation in the two media. Unidirectional Ca2+ influx of sarcoplasmic reticulum near steady state of Ca2+ uptake was measured by pulse labeling with 45Ca2+. The Ca2+ efflux rate was then determined by subtracting the net uptake from the influx rate. At the first plateau of Ca2+ uptake in normal medium, Ca2+ influx was balanced by Ca2+ efflux with an exchange rate of 240 nmol/mg per min. This exchange rate was maintained relatively constant at the plateau phase. In modified medium, the Ca2+ exchange rate at the first plateau of Ca2+ uptake was about half of that in normal medium. When the second phase of Ca2+ uptake was initiated, both the influx and efflux rates started to increase and reached a similar exchange rate as observed in normal medium. Also, during the second phase of Ca2+ uptake, the difference between the influx and efflux rates continued to increase until the second plateau phase was approached. In conditions where the formation of ADP and inorganic phosphate was minimized by using a low concentration of sarcoplasmic (7.5 micrograms/ml) and/or using acetyl phosphate instead of ATP, the second phase of Ca2+ uptake was also observed. These data suggest that the Ca2+ load attained by sarcoplasmic reticulum vesicles during active transport is modulated by ADP accumulated from ATP hydrolysis. ADP probably exerts its effect by facilitating Ca2+ efflux, which subsequently stimulates Ca2+ exchange.

Ouabain binding and coupled sodium, potassium, and chloride transport in isolated transverse tubules of skeletal muscle.

The affinity and number of binding sites of [3H]ouabain to isolated transverse (T) tubules were determined in the absence and presence of deoxycholate. In both conditions the KD was approximately 53 nM while deoxycholate increased the number of binding sites from 3.5 to 37 pmol/mg protein. We concluded that the ouabain binding sites were located primarily on the inside of the isolated vesicle and that the vesicles were impermeable to ouabain. ATP induced a highly active Na+ accumulation by the T tubules which increased Na+ in the T tubular lumen by almost 200 nmol/mg protein. The accumulation had an initial fast phase lasting 2-3 min and a subsequent slow phase which continued for at least 40 min. The rate of the initial fast phase indicated a turnover number of 20 Na+/s. The Na+ accumulation was prevented by monensin but was unaffected by valinomycin. Ouabain did not influence Na+ uptake, but digitoxin inhibited it. At low K+ the accumulation of Na+ was reduced 3.7-fold below the value at 50 mM K+. 86Rb, employed as a tracer to detect K+, showed a first phase of K+ release while Na+ was accumulated. After 2-3 min, K+ was reaccumulated while Na+ continued to increase in the lumen. T tubules accumulated Cl- on addition of ATP. This suggested that ATP initiated an exchange of Na+ for K+ followed by uptake of Na+ and K+ accompanied by Cl-.

Electrophysiological effects of mexiletine (Kö1173) on ovine cardiac Purkinje fibers.

To clarify the electrophysiological mechanisms of the antiarrhythmic effects of mexiletine, we examined the actions of mexiletine (0.1--30 mg/l) on action potential characteristics (phase 0 amplitude, overshoot, maximum upstroke velocity, maximum diastolic and activation voltages, duration at 50% and 90% repolarization) of cardiac Purkinje fibers using standard microelectrode techniques. In fibers stimulated at constant rate, mexiletine decreased phase 0 amplitude and Vmax and shortened the action potential. Mexiletine shortened action potential duration at lower concentrations than those which altered phase 0 depolarization. The effect of mexiletine on normal automaticity in cardiac Purkinje fibers was studied in fibers made automatic either by hypokalemia or by isoproterenol. Mexiletine suppressed normal automaticity by shifting activation voltage, so that spontaneous phase 4 depolarization reached a stable resting voltage without triggering regenerative phase 0 depolarization. The effects of mexiletine on abnormal automaticity were studied in Purkinje fibers intoxicated by ouabain. Mexiletine decreased the amplitude of or abolished either early or delayed after depolarizations induced by ouabain.