Linear electric field mass analysis: a technique for three-dimensional high mass resolution space plasma composition measurements

A revolutionary type of three-dimensional space plasma composition analyzer has been developed that combines very high-resolution mass composition measurements on a fraction of the incident ions simultaneously with lower mass resolution but high sensitivity measurements of the remaining population in a single compact and robust sensor design. Whereas the lower mass resolution measurements are achieved using conventional energy/charge (E/q) and linear time-of-flight analysis, the high mass resolution measurements are made by timing reflected E/q analyzed ions in a linear electric field (LEF). In a LEF the restoring (reflecting) force that an ion experiences in the direction parallel to the field is proportional to the depth it travels into the LEF region, and its equation of motion in that direction is that of a simple harmonic oscillator. Consequently, an ion's travel time is independent of its initial angle and energy and is simply proportional to the square root of the ion's mass/charge (m/q). The measured m/q resolution, (m/q)/Delta(m/q), for a small LEF-based prototype that we have developed and tested is approximately 20. In addition, our laboratory measurements with the prototype instrument show that characteristic time-of-flight spectra allow the resolution of atomic and molecular species with nearly identical m/q values. The measured response of the prototype is in excellent agreement with computer simulations of the device. Advanced design work using this computer simulation indicates that three-dimensional plasma composition analyzers with m/q resolutions of at least 50 are readily achievable.     

A case of sarcoidosis with atypical high resolution CT findings]

A 36-year-old woman was referred to our hospital for investigation of erythema on the upper arms and thighs and abnormal radiological findings in the chest. A chest radiograph showed poorly defined fine nodules in both lung fields and high-resolution CT revealed fine nodular opacities with a random distribution throughout both lungs. No lymph node enlargement or peribronchovascular interstitial thickening were seen. Bronchoscopic evaluation revealed bronchial mucosal hypervascularity. Transbronchial lung biopsy and skin biopsy specimens showed noncaseating epithelioid cell granulomas. These findings confirmed the diagnosis of sarcoidosis. This is a rare case of sarcoidosis presenting with atypical high-resolution CT findings, which are difficult to differentiate from those of miliary tuberculosis or metastatic carcinoma.     

Organelle proteomics: implications for subcellular fractionation in proteomics

Functional proteome analysis is not restricted to the sequence information but includes the broad spectrum of structural modifications and quantitative changes of proteins to which they are subjected in different tissues and cell organelles and during the development of an organism. Cell biology has provided the means required for the analysis of the composition and properties of purified cellular elements. Subcellular fractionation is an approach universal across all cell types and tissues, including cardiac and vascular system. Subcellular fractionation and proteomics form an ideal partnership when it comes to enrichment and analysis of intracellular organelles and low abundant multiprotein complexes. Subcellular fractionation is a flexible and adjustable approach resulting in reduced sample complexity and is most efficiently combined with high-resolution 2D gel/mass spectrometry analysis as well as with gel-independent techniques. In this study we introduce state of the art subcellular fractionation techniques and discuss their suitability, advantages, and limitations for proteomics research.     

以"垂体占位"为影像学表现并自发缓解的淋巴细胞性垂体炎一例

淋巴细胞性垂体炎(LyH)是一种少见的自身免疫病,本文报道1例影像显示"垂体占位"并自发缓解的LyH患者,经临床观察及文献复习,有理由认为对于临床症状轻微、占位效应不明显者,随访观察或生理剂量替代治疗可能是更加个体化的治疗策略。     

Churg-Strauss syndrome: high resolution CT and pathologic findings

OBJECTIVES: The purpose of this study was to evaluate high-resolution CT findings in 7 patients with Churg-Strauss syndrome and to compare the CT with the histopathologic findings. MATERIALS AND METHODS: High-resolution CT scans of 7 asthmatic patients (4 women, 3 men, age range, 34-62 years, mean 49 years) with Churg-Strauss syndrome were reviewed by 2 observers. Histologic specimens of lung obtained at surgical (n = 3) or transbronchial (n = 3) biopsy or autopsy (n = 1) were reviewed by an expert lung pathologist. The diagnosis of Churg-Strauss was based on clinical, laboratory, and histologic findings. RESULTS: Parenchymal and airway abnormalities included ground-glass opacities (n = 5), areas of air-space consolidation (n = 4), centrilobular nodules (n = 5), nodules 1-3 cm in diameter (n = 3), interlobular septal thickening (n = 4), bronchial wall thickening (n = 4), and areas of atelectasis (n = 1). Surgical biopsy (n = 3) and autopsy (n = 1) specimens demonstrated airspace disease in 3 patients, interlobular septal thickening in 3 patients, and airway abnormalities in 2 patients. Histologically, the airspace disease included eosinophilic pneumonia (n = 2) and small foci of organizing pneumonia (n = 1). The septal thickening was due to edema combined with numerous (n = 2) or few (n = 1) eosinophils. The airway abnormalities (n = 2) included muscle hypertrophy and large airway wall necrosis (n = 1) and eosinophilic infiltration of the airway walls (n = 1). Transbronchial biopsy (n = 3) demonstrated increased eosinophils. CONCLUSION: The main high-resolution CT findings of Churg-Strauss syndrome consist of airspace consolidation or ground-glass opacities, septal lines, and bronchial wall thickening. These reflect the presence of eosinophilic infiltration of the airspaces, interstitium, and airways, and interstitial edema.     

Emergency response to a smallpox attack: the case for mass vaccination

In the event of a smallpox bioterrorist attack in a large U.S. city, the interim response policy is to isolate symptomatic cases, trace and vaccinate their contacts, quarantine febrile contacts, but vaccinate more broadly if the outbreak cannot be contained by these measures. We embed this traced vaccination policy in a smallpox disease transmission model to estimate the number of cases and deaths that would result from an attack in a large urban area. Comparing the results to mass vaccination from the moment an attack is recognized, we find that mass vaccination results in both far fewer deaths and much faster epidemic eradication over a wide range of disease and intervention policy parameters, including those believed most likely, and that mass vaccination similarly outperforms the existing policy of starting with traced vaccination and switching to mass vaccination only if required.     

Unbiased quantitative proteomics of lipid rafts reveals high specificity for signaling factors

Membrane lipids were once thought to be homogenously distributed in the 2D surface of a membrane, but the lipid raft theory suggests that cholesterol and sphingolipids partition away from other membrane lipids. Lipid raft theory further implicates these cholesterol-rich domains in many processes such as signaling and vesicle traffic. However, direct characterization of rafts has been difficult, because they cannot be isolated in pure form. In the first functional proteomic analysis of rafts, we use quantitative high-resolution MS to specifically detect proteins depleted from rafts by cholesterol-disrupting drugs, resulting in a set of 241 authentic lipid raft components. We detect a large proportion of signaling molecules, highly enriched versus total membranes and detergent-resistant fractions, which thus far biochemically defined rafts. Our results provide the first large-scale and unbiased evidence, to our knowledge, for the connection of rafts with signaling and place limits on the fraction of plasma membrane composed by rafts.     

Accuracy of staging in early oesophageal cancer using high resolution endoscopy and high resolution endosonography: a comparative, prospective, and blinded trial

BACKGROUND AND AIMS: The increasing use of endoscopic resection for curative treatment of early oesophageal cancers requires accurate staging before therapy. In a prospective blinded trial, we compared staging of early oesophageal carcinoma using high resolution endoscopy (HR-E) with staging using high resolution endosonography (HR-EUS). PATIENTS AND METHODS: A total of 100 patients (89 men, 11 women; mean age 63.9 (10.8) years (range 31-91)) with a suspicion of early oesophageal adenocarcinoma (n = 81) or squamous cell carcinoma (n = 19) were enrolled in the study. After endoscopic staging with high resolution video endoscopy by two experienced endoscopists, HR-EUS was performed by an experienced endosonographer who was blinded to the endoscopic assessment. Results of the staging examinations were correlated with the histology of the resected tumours. RESULTS: Overall rates for accuracy of the endoscopic and endosonographic staging were 83.4% and 79.6%, respectively. Sensitivity for mucosal tumours (n = 68) was more than 90% (EUS 91.2%, endoscopy 94.1%) while sensitivity for submucosal tumours (n = 25) was lower, at 48% for EUS and 56% for endoscopic staging. A combination of the two techniques increased the sensitivity for submucosal tumours to 60%. Submucosal tumours in the tubular oesophagus were significantly better staged with HR-EUS than submucosal tumours close to the oesophagogastric junction (10/11 v 2/14; p<0.001). Tumours infiltrating the second and third submucosal layers were also more correctly diagnosed than tumours with slight infiltration of the first submucosal layer (sm1). CONCLUSIONS: The overall diagnostic accuracy of both HR-E and HR-EUS with a 20 MHz miniprobe in early oesophageal cancer was high (approximately 80%), with no significant differences between the two techniques. HR-E and HR-EUS provide a high level of diagnostic accuracy for mucosal tumours and submucosal tumours located in the tubular part of the oesophagus. With submucosal tumours located at the oesophagogastric junction or with infiltration of the first third of the submucosa however, the diagnostic accuracy of both techniques is not yet satisfactory.     

The accuracy and spatial resolution of the measurement of tissue oxygen removal rate.

An analysis is presented of factors determining the accuracy and spatial resolution of a method for the estimation of oxygen removal rate in tissues using a multi-cathode electrode placed on the tissue surface. The effect of oxygen consumption by the cathodes is shown to be small for 25-micrometer diameter cathodes, but covering the tissue surface with a thin oxygen oxygen-permeable plastic film can introduce a systematic error into the estimate of removal rate, the size of which depends upon the oxygen diffusion coefficient and solubility in the plastic compared with those in the tissue. Spatial resolution is shown to be adequate for distinguishing changes in removal rate over distances of a few hundred microns, and the averaging of removal rate in the direction normal to the tissue surface is weighted heavily towards the superficial tissue layer.     

Method for obtaining a high resolution protein map starting from a low resolution map.

A method is described for estimating the phases of high resolution single-crystal diffraction data from proteins, by using as a starting point a set of low resolution phases (about 3 A) derived by multiple isomorphous replacement (or other) methods. The method consists in refining by least-squares the positions and thermal parameters of a set of dummy atoms placed in the initial low resolution electron density map, so as to minimize the discrepancy between the calculated scattering intensities and the scattering intensities observed in the high resolution data set. Phases calculated from these refined atomic positions are used to extend the resolution and to improve the quality of the electron density map. The success of the method depends on a new least-squares algorithm that has a radius of convergence of about 0.75 A. This large radius of convergence, together with the severe restrictions placed on the initial positions of the dummy atoms by the requirement that they lie within limited regions of the isomorphous electron density map, and the constraint imposed by the polymeric nature of a polypeptide chain account for the success of the method. The method has been successfully used to phase the structure factors of 2-zinc insulin at a resolution of 2 A and 1.5 A, starting from a set of isomorphous phases at 3-A resolution.     

Bone mass measurements the case for selected screening?

Osteoporosis, a consequence of loss of bone mass, results in serious health and economic problems, particularly fractures of the hip and spine. Fractures are, in the majority of cases, the result of low bone mineral density (BMD). Technology is now available that allows accurate and sensitive measurement of BMD. The state of the art technology is dual x-ray absorptiometry (DXA), which, unfortunately, is not widely available and is relatively expensive. BMD measurement by DXA is the most individually objective predictor of fracture risk and, therefore, may be a reasonable method for universal screening of women. The pros and cons of mass screening to identify women with low bone mass and increased fracture risk are discussed. (Trends Endocrinol Metab 1997;8:157-160). (c) 1997, Elsevier Science Inc.     

Precision, accuracy, and user acceptance of the OneTouch SelectSimple blood glucose monitoring system

Background

The OneTouch® SelectSimple™ blood glucose monitoring system (BGMS) is a device for self-monitoring of blood glucose designed for ease of use. Alarms alert subjects to low [20–69 mg/dl (1.1–3.8 mmol/liter)], high [180–239 mg/dl (9.9–13.2 mmol/liter)], and very high [240–600 mg/dl (13.3–33.1 mmol/liter)] blood glucose readings.

Methods

Repeatability in blood and intermediate precision with aqueous controls were examined using blood from one donor adjusted to different glucose concentrations, and tested with 10 meters and 1 test-strip lot. System accuracy was evaluated with blood samples from 100 diabetes patients tested on 3 test-strip lots, compared with a reference system (YSI 2300 STAT). To test user accuracy, patients (n = 156) and health care professionals (HCPs) tested subject blood with the SelectSimple twice. Health care professionals evaluated subject BGMS technique after a 3–5 day home-testing period. Users evaluated the instructions for use and responded to a user acceptance questionnaire.

Results

In repeatability and intermediate precision testing, the SelectSimple BGMS had a coefficient of variation of ≤5% or standard deviation of ≤5 mg/dl. In the clinical accuracy study, 100% of measurements <75 mg/dl (4.2 mmol/liter) were within ±15 mg/dl (0.8 mmol/liter) of reference value, and 99.6% of measurements ≥75 mg/dl (4.2 mmol/liter) were within ±20%. Patients were able to use the BGMS appropriately and evaluated it as easy to use. Acceptance of the SelectSimple BGMS was within predefined limits.

Conclusions

In these studies, the SelectSimple BGMS met all criteria for precision, system, and user accuracy, was easy to use, and was well accepted by patients.     

中国高分辨率食管测压临床操作指南(成人)

高分辨率食管测压(HREM)是诊断食管动力障碍疾病的金标准。准确的诊断建立在规范的操作之上。为了提高HREM的操作质量,中国医师协会消化医师分会胃食管反流病专业委员会牵头制定本指南。通过邀请国内相关领域专家对国内外有关文献进行检索、讨论,并召开2次专家研讨会,确定了指南的内容。本指南内容涉及HREM的适应证和禁忌证、详细的操作指导,以及结果阐述。