Three dimensional characterisation of chromatography bead internal structure using X-ray computed tomography and focused ion beam microscopy.

X-ray computed tomography (CT) and focused ion beam (FIB) microscopy were used to generate three dimensional representations of chromatography beads for quantitative analysis of important physical characteristics including tortuosity factor. Critical-point dried agarose, cellulose and ceramic beads were examined using both methods before digital reconstruction and geometry based analysis for comparison between techniques and materials examined. X-ray 'nano' CT attained a pixel size of 63 nm and 32 nm for respective large field of view and high resolution modes. FIB improved upon this to a 15 nm pixel size for the more rigid ceramic beads but required compromises for the softer agarose and cellulose materials, especially during physical sectioning that was not required for X-ray CT. Digital processing of raw slices was performed using software to produce 3D representations of bead geometry. Porosity, tortuosity factor, surface area to volume ratio and pore diameter were evaluated for each technique and material, with overall averaged simulated tortuosity factors of 1.36, 1.37 and 1.51 for agarose, cellulose and ceramic volumes respectively. Results were compared to existing literature values acquired using established imaging and non-imaging techniques to demonstrate the capability of tomographic approaches used here.

Laser-preparation of geometrically optimised samples for X-ray nano-CT.

A robust and versatile sample preparation technique for the fabrication of cylindrical pillars for imaging by X-ray nano-computed tomography (nano-CT) is presented. The procedure employs simple, cost-effective laser micro-machining coupled with focused-ion beam (FIB) milling, when required, to yield mechanically robust samples at the micrometre length-scale to match the field-of-view (FOV) for nano-CT imaging. A variety of energy and geological materials are exhibited as case studies, demonstrating the procedure can be applied to a variety of materials to provide geometrically optimised samples whose size and shape are tailored to the attenuation coefficients of the constituent phases. The procedure can be implemented for the bespoke preparation of pillars for both lab- and synchrotron-based X-ray nano-CT investigations of a wide range of samples.

Biodistribution of 99mTc-MAA on SPECT/CT performed for 90Y radioembolization therapy planning: a pictorial review.

Purpose: To evaluate the frequency of 99mTc-MAA uptake in extrahepatic organs during 90Y radioembolization therapy planning. Methods: This retrospective case series of 70 subjects who underwent 99mTc-MAA hepatic artery perfusion studies between January 2014 and July 2016 for 90Y radioembolization therapy planning at our institution involved direct image review for all subjects, with endpoints recorded: lung shunt fraction, extrahepatic radiotracer uptake, time from MAA injection to imaging. Results: Combined planar and SPECT/CT imaging findings in the 70 subjects demonstrated lung shunt fraction measurements of less than 10% in 53 (76%) subjects and greater than 10% in 17 (24%) subjects. All patients demonstrated renal cortical uptake, 23 (33%) demonstrated salivary gland uptake, 23 (33%) demonstrated thyroid uptake, and 32 (46%) demonstrated gastric mucosal uptake, with significant overlap between these groups. The range of elapsed times between MAA injection and initial imaging was 41-138 min, with a mean of 92 min. There was no correlation between time to imaging and the presence of extrahepatic radiotracer uptake at any site. Conclusions: During hepatic artery perfusion scanning for 90Y radioembolization therapy planning, extrahepatic uptake is common, particularly in the kidney, salivary gland, thyroid and gastric mucosa, and is hypothesized to result from breakdown of 99mTc-MAA over time. Given the breakdown to smaller aggregates and ultimately pertechnetate, this should not be a contraindication to actual Y-90 microsphere therapy. Although we found no correlation between time to imaging and extrahepatic uptake, most of our injection to imaging times were relatively short.

Antiproton stopping power data for radiation therapy simulations.

Stopping powers of H, He, H2, and H2O targets for antiprotons have been calculated using a convergent close-coupling method. For He and H2 targets electron-electron correlations are fully accounted for using a multiconfiguration approximation. Two-electron processes are included using an independent-event model. The water molecule is described using a neon-like structure model with a pseudo-spherical potential. Results are tabulated for the purpose of Monte Carlo simulations to model antiproton transport through matter for radiation therapy.

Endoscopic full-thickness resection of gastric tumors using a novel grasp-and-snare technique: feasibility in ex vivo and in vivo porcine models.

BACKGROUND AND STUDY AIMS: Endoscopic full-thickness resection (EFTR) is a less-invasive method of en bloc removal of gastrointestinal tract tumors. The aim of this study was to evaluate the feasibility of a grasp-and-snare EFTR technique using a novel tissue-lifting device that provides more secure tissue anchoring and manipulation. METHODS: EFTR of normal gastric tissue and model stomach tumors was performed using a double-channel therapeutic endoscope with a prototype tissue-lifting device through one channel and a prototype hexagonal snare through the other. The lifting device was advanced through the open snare and anchored to the gastric wall immediately adjacent the model tumor. The tissue-lifting device was then partially retracted into the endoscope, causing the target tissue, including tumor, to evert into the gastric lumen. The open snare was then placed distal to the tumor around uninvolved gastric tissue. Resection was performed with a blended electrosurgical current through the snare. In the live pigs, EFTR was followed by laparotomy to asses for complications. RESULTS: 24 EFTRs were performed -- 14 in explanted stomachs and 10 in live pigs. In total, 23/24 resections resulted in full-thickness gastric defects. Resection specimens measured up to 5.0 cm when stretched and pinned on a histology stage. Gross margins were negative in 17/20 model tumor resections. Two resections were complicated by gastric mural bleeding. There was no evidence of adjacent organ injury. CONCLUSIONS: EFTR of gastric tumors using the grasp-and-snare technique is feasible in pigs. This technique is advantageous in that eversion of the gastric wall avoids injury to external organs, continuous luminal insufflation is not required, and the involved techniques are familiar to endoscopists. Additional research is necessary to further evaluate safety and reliable closure.

Utility of current risk stratification tests for predicting major arrhythmic events after myocardial infarction.

OBJECTIVES: We surveyed the literature to estimate prediction values for five common tests for risk of major arrhythmic events (MAEs) after myocardial infarction. We then determined feasibility of a staged risk stratification using combinations of noninvasive tests, reserving an electrophysiologic study (EPS) as the final test. BACKGROUND: Improved approaches are needed for identifying those patients at highest risk for subsequent MAE and candidates for implantable cardioverter-defibrillators. METHODS: We located 44 reports for which values of MAE incidence and predictive accuracy could be inferred: signal-averaged electrocardiography; heart rate variability; severe ventricular arrhythmia on ambulatory electrocardiography; left ventricular ejection fraction; and EPS. A meta-analysis of reports used receiver-operating characteristic curves to estimate mean values for sensitivity and specificity for each test and 95% confidence limits. We then simulated a clinical situation in which risk was estimated by combining tests in three stages. RESULTS: Test sensitivities ranged from 42.8% to 62.4%; specificities from 77.4% to 85.8%. A three-stage stratification yielded a low-risk group (80.0% with a two-year MAE risk of 2.9%), a high-risk group (11.8% with a 41.4% risk) and an unstratified group (8.2% with an 8.9% risk equivalent to a two-year incidence of 7.9%). CONCLUSIONS: Sensitivities and specificities for the five tests were relatively similar. No one test was satisfactory alone for predicting risk. Combinations of tests in stages allowed us to stratify 91.8% of patients as either high-risk or low-risk. These data suggest that a large prospective study to develop a robust prediction model is feasible and desirable.

Dysrhythmia hazard after hospitalization for myocardial infarction: two ECG prognostic methods compared.

We retrieved reports of heart rate variability and signal-averaged electrocardiograms (SAECG) used to predict risk of a dysrhythmic event. From each report the number of cases with and without events was extracted to establish accurate values for true positive rate (tpr = sensitivity) and false positive rate (fpr = 1 minus specificity). For all the heart rate variability reports, these values were collected and tpr values were plotted versus fpr. The (fpr,tpr) data were summarized by a meta ROC graph using the method of Moses and Shapiro. A composite weighted mean value and 95% confidence interval were also derived. A summary meta-ROC curve for the SAECG reports was similarly obtained., Meta-ROC analysis of multiple reports better summarizes the performances of different prognostic methods and allows the effect of combining tests for a larger population to be simulated.

Neurally mediated cardiac syncope: autonomic modulation after normal saline infusion.

OBJECTIVES: This study assessed the heart variability response to orthostatic stress during tilt table testing before and after normal saline administration. BACKGROUND: The efficacy of sodium chloride and mineralocortoid in the treatment of neurally mediated cardiac syncope is attributed to intravascular volume expansion; however, their modulation of autonomic nervous system activity has not been evaluated. METHODS: Heart rate variability analysis was performed on 12 adolescents with a history of syncope or presyncope (mean age 15.2+/-0.7 years) during tilt table testing. Subjects were upright 80 degrees for 30 min or until syncope. After normal saline administration, the patient was returned upright for 30 min. Heart rate variability analysis data were analyzed by an autoregression model (Burg method). RESULTS: All subjects reproducibly developed syncope during control tilt table testing; median time to syncope was 9.4+/-2.1 min. After normal saline infusion, none of the subjects developed syncope after 30 min upright. In the control tilt, there was an initial increase followed by a progressive decrease in low frequency power until syncope. Repeat tilt after normal saline administration demonstrates that low frequency power increased but the magnitude of initial change was blunted when compared with control. In addition, low frequency power increased during normal saline tilt sequence compared with the control tilt, during which it decreased. CONCLUSIONS: Normal saline blunted low frequency power stimulation and prevented paradoxical low frequency power (sympathetic) withdrawal. Increasing intravascular volume with normal saline alters autonomic responses that may trigger neurally mediated syncope reflexes.

NHLBI workshop on the utilization of ECG databases: preservation and use of existing ECG databases and development of future resources.

Baseline examinations and periodic reexaminations in longitudinal population studies, together with ongoing surveillance for morbidity and mortality, provide unique opportunities for seeking ways to enhance the value of the electrocardiogram (ECG) recorded with digital technology as an inexpensive and noninvasive tool for prognosis and diagnosis. Clinicians, epidemiologists, and engineers from industry, government, and academic medical centers gathered at a workshop sponsored by the National Heart, Lung, and Blood Institute (NHLBI) on June 11-12, 1997, to discuss the research potential of ECG databases, their preservation and accession, and standards for recording and storage. Databases considered were those acquired in ongoing and future NHLBI-funded studies and in clinical settings in which the ECG continues to provide valuable information for evaluation and treatment. The accessibility of existing databases, the quality of their data, and the availability of ancillary demographic and clinical information were major themes. Also discussed were appropriate statistical methodologies to be used with these data for developing and testing ECG algorithms. The workshop participants affirmed the value of these databases and urged the establishment of an ECG advisory and review group to (1) resolve technical and proprietary issues for the utilization of currently existing databases; (2) develop standards for recording, storage, and utilization of ECGs in future NHLBI-supported studies; (3) oversee the creation of a national ECG database resource, consisting of an archive of ECG databases from past and ongoing NHLBI-supported studies, and a registry of ECG databases that would eventually include digital ECGs from populations currently underrepresented in the demographic spectrum of the NHLBI databases.

Panoramic display of the orderly sequenced 12-lead ECG.

The standard 12-lead electrocardiogram (ECG) has been developed over many years. The ECG has had a long and successful history of providing diagnostic information in clinical medicine. Cardiac arrhythmias have been elucidated by deductive reasoning from continuous ECG recordings with confirmation from electrophysiologic studies. Recently, there has been renewed interest in the morphology of the QRS complex, ST-segment, and T wave, which raises the important question of considering whether the usual method of display provides maximal diagnostic capabilities. The conventional display provides a logical visualization of precordial lead recordings representing the horizontal plane, but does not provide a logical visualization of the limb lead recordings representing the frontal plane. Many clinical problems require the consideration of serial ECGs necessitating the comparison of separate pages. An alternate format presenting serial recordings on a single page would be advantageous. Some automated ECG analysis systems already include the capability for multiple display formats, but these have not yet been widely used in clinical practice. This point of view paper introduces a new display format for the standard 12-lead ECG that includes: (1) a presentation of an orderly sequence of leads to facilitate scanning through different points in space and (2) a presentation of recordings of 12-lead sequences to facilitate scanning through different points in time. This display format could either replace or supplement the conventional ECG format.

Specialist outreach clinics in general practice.

OBJECTIVES: To establish the extent and nature of specialist outreach clinics in primary care and to describe specialists' and general practitioners' views on outreach clinics. DESIGN: Telephone interviews with hospital managers. Postal questionnaire surveys of specialists and general practitioners. SETTING: 50 hospitals in England and Wales. SUBJECTS: 50 hospital managers, all of whom responded. 96 specialists and 88 general practitioners involved in outreach clinics in general practice, of whom 69 (72%) and 46 (52%) respectively completed questionnaires. 122 additional general practitioner fundholders, of whom 72 (59%) completed questionnaires. MAIN OUTCOME MEASURES: Number of specialist outreach clinics; organisation and referral mechanism; waiting times; perceived benefits and problems. RESULTS: 28 of the hospitals had a total of 96 outreach clinics, and 32 fundholders identified a further 61 clinics. These clinics covered psychiatry (43), medical specialties (38), and surgical specialties (76). Patients were seen by the consultant in 96% (107) of clinics and general practitioners attended at only six clinics. 61 outreach clinics had shorter waiting times for first outpatient appointment than hospital clinics. The most commonly reported benefits for patients were ease of access and shorter waiting times. CONCLUSIONS: Specialist outreach clinics cover a wide range of specialties and are popular, especially in fundholding practices. These clinics do not seem to have increased the interaction between general practitioners and specialists.

Improved detection of echocardiographic left ventricular hypertrophy using a new electrocardiographic algorithm.

OBJECTIVES: The purpose of this study was to use the Framingham data base to devise and test an improvement in an electrocardiographic (ECG) voltage criterion for detecting left ventricular hypertrophy that is gender specific and adjusts for age and obesity. BACKGROUND: Electrocardiographic detection of left ventricular hypertrophy has been receiving increasing attention. The "Cornell" ECG voltage, defined as the sum of voltages for the R wave of lead aVL and S wave of lead V3, has been shown to correlate strongly with echocardiographically estimated left ventricular mass. Because the magnitude of this voltage varies with both age and obesity, we have proposed a simple formula for its adjustment for these two variables. METHODS: Using linear regression, the adjustment formula was estimated from data on 1,468 men and 1,883 women from the Framingham Heart Study cohort who were free of myocardial infarction and who had both an ECG and an echocardiogram recorded during the same clinic examination. A modified receiver operating characteristic curve method was used to compare sensitivities at the same specificity levels. The adjustment formula was estimated from one randomly chosen half of the study cohort and applied to the other half for evaluation. RESULTS: Significant improvement in sensitivity for the detection of left ventricular hypertrophy was realized at all levels of specificity. At a specificity level of 98%, the adjustment increased the sensitivity of the Cornell voltage from 10% to 17% in men and from 12% to 22% in women. For severe hypertrophy, defined as a left ventricular mass > 3 SD above the gender-specific mean, the sensitivity increased from 23% to 38% for men and from 22% to 55% for women at a specificity level of 95%. CONCLUSIONS: This approach can substantially enhance the utility of the ECG for the detection of left ventricular hypertrophy. If these results are validated in other population groups, this approach may prove valuable in the screening of hypertensive populations and for the monitoring of patients undergoing treatment for hypertension.

A kinetic model of CD4+ lymphocytes with the human immunodeficiency virus (HIV).

This report describes a kinetic model of in vitro cytopathology involving interactions of human immunodeficiency virus (HIV) with CD4+ helper T lymphocytes. The model uses nonlinearly coupled, ordinary differential equations to simulate the dynamics of infected and uninfected cells and free virions. It is assumed that resting cells are more readily infected than activated cells, but once infected, only activated cells produce more virus. Resting cells can be activated by some appropriate stimulus (e.g. phytohemagglutinin, soluble antigen). The model predicts that the initial inoculum of virus is taken up by resting cells and without stimulation the system comes to a steady state of two populations, namely infected and uninfected cells. Stimulation of this system produces two additional populations, namely infected and uninfected activated cells which, along with the previous populations, exhibit cyclic behavior of growth, viral expression/release, and death. Additional stimuli enhance or diminish the cyclic behavior depending upon their occurrence in time. These simulations suggest a similar dynamics in human HIV infection and may explain a major factor responsible for the widely varying depletion rate of (CD4+) helper T cells in AIDS patients.

A filter to suppress ECG baseline wander and preserve ST-segment accuracy in a real-time environment.

Accurate monitoring of the ST-segment displacements in real-time environments can be distorted by the nonlinear phase response of a baseline filter such as the single-pole, high-pass (0.5 Hz) filter that is standard in the industry today. The authors have previously constructed a four-pole null phase (1.0 Hz) filter that is nearly ideal in suppressing baseline wander while preserving ST-segment accuracy; however, this foreward/backward filter requires capture of a large ECG segment before filtering, thereby producing a delay that is unacceptable in a real-time environment. As a practical compromise, a two-pole, phase-compensated (1.0 Hz) filter was constructed while introducing a small time delay (160 ms). It performs much better than the "standard filter" and almost as well as the "ideal" filter in several tests, namely (1) suppression of baseline wander in a series of ECGs, (2) suppression of artificial baseline, (3) response to a triangular impulse wave (American Heart Association test), and (4) J-point displacement in several ECGs.