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Comparison of competing risks failure time methods and time-independent methods for assessing strain variations in vaccine protection.

In a preventive vaccine efficacy trial of a vaccine for a genotypically and phenotypically diverse pathogen, it is important to assess if and how vaccine protection against infection or disease varies with characteristics of the exposing pathogen. Gilbert, Self and Ashby developed statistical methods for this problem when the outcome data are counts of the number of vaccinated and unvaccinated trial participants infected by each pathogen strain. However, in many vaccine trials time-to-case information is available, and the extent to which this information improves investigation of differential vaccine protection is unclear. We describe how cause-specific proportional hazards models and other popular competing risks failure time techniques can be applied to this problem. This includes new results on the assumptions required for these methods to give valid inferences about strain-specific vaccine efficacy, and a comparison of theoretical and finite-sample properties between these methods and the time-independent methods. Theoretical considerations, a cholera vaccine trial example, and an extensive simulation study of a human immunodeficiency virus type 1 (HIV-1) vaccine trial show that information about failure times does not appreciably improve estimation or testing unless the pathogen has a high attack rate and the relative prevalence of pathogen strains shifts substantially during the trial follow-up period. An important implication is that practically optimal evaluation of strain-specific vaccine efficacy in HIV-1 vaccine trials will not require knowledge of infection times.

AIDS Vaccines↗

Routine or selective carotid artery shunting for carotid endarterectomy (and different methods of monitoring in selective shunting).

BACKGROUND: Temporary interruption of blood flow during carotid endarterectomy can be avoided by using a shunt across the clamped section of the carotid artery. This may improve outcome. OBJECTIVES: The objective of this review was to assess the effect of routine versus selective shunting during carotid endarterectomy, and to assess the best method for selecting patients for shunting. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register, Medline (1966 to 1994), Embase (1980 to 1995) and Index to Scientific and Technical Proceedings (1980 to 1994). We handsearched Annals of Surgery (1981 to 1995), British Journal of Surgery (1985 to 1995), European Journal of Vascular Surgery (1988 to 1995) and World Journal of Surgery (1978 to 1995). SELECTION CRITERIA: Randomised and quasi-randomised trials of routine shunting compared with no shunting, and trials that compared different shunting policies in patients undergoing carotid endarterectomy. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied the inclusion criteria. The data were extracted by one reviewer and double-checked. Trial quality was assessed. MAIN RESULTS: Three trials were included. Two trials involving 590 patients compared routine shunting with no shunting. The other trial involving 131 patients compared shunting with a combination of electroencephalographic and carotid pressure measurement, with shunting by carotid pressure measurement alone. Allocation was adequately concealed in one trial, and one trial was quasi-randomised. Analysis was by intention-to-treat where possible. For routine versus no shunting, there was no significant difference in the rate of all stroke, ipsilateral stroke or death up to 30 days after surgery, although data were limited. There was no significant difference between the risk of ipsilateral stroke in patients selected for shunting with the combination of electroencephalographic and carotid pressure assessment compared to pressure assessment alone, although again the data were limited. REVIEWER'S CONCLUSIONS: The data presently available are too limited to either support or refute the use of routine or selective shunting in carotid endarterectomy. Large scale randomized trials using no shunting as the control group are required. No one method of monitoring in selective shunting has been shown to produce better outcomes.

Arteriovenous Shunt, Surgical↗

Heparin, low molecular weight heparin and physical methods for preventing deep vein thrombosis and pulmonary embolism following surgery for hip fractures.

BACKGROUND: Hip fracture patients have a high risk of thromboembolic complications following surgical management. OBJECTIVES: To examine the effects of heparin (unfractionated (U), and low molecular weight (LMW) heparins), and physical methods (compression stockings, calf or foot pumps) for prevention of deep venous thrombosis (DVT) and pulmonary embolism after surgery for hip fracture in the elderly. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group trials register, Medline, Embase, and reference lists of published papers and books. We contacted trialists and other workers in the field. Date of most recent search: September 1996. SELECTION CRITERIA: Randomised and quasi-randomised trials evaluating the use of heparins and physical agents for prevention of DVT and pulmonary embolism in patients undergoing surgery for hip fracture. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed methodological quality and extracted data. Trials were grouped into four categories (heparin versus control, mechanical versus control, LMW heparin versus U heparin, and miscellaneous) and results pooled where possible. MAIN RESULTS: The 26 included trials involved 2600 predominantly female and elderly patients. Overall, trial quality was disappointing. Ten trials involving 826 patients which compared U heparin with control, and four trials of 471 patients which compared LMW heparin with control, showed a reduction in the incidence of lower limb DVT (121/511 (24%) versus 203/519 (39%); Peto odds ratio 0.41; 95% confidence interval 0.31 to 0.55). There were insufficient data to confirm the efficacy of either agent in the prevention of pulmonary embolism. There was a non significant increase in overall mortality in the heparin group (46/420 (11%) versus 35/423 (8%); Peto odds ratio 1.39; 95% confidence interval 0. 86 to 2.23). Data were inadequate for all other outcomes including wound complications. There is insufficient evidence from five trials, involving 644 patients, to establish if LMW heparin was superior to U heparin. Most trials evaluating heparins had methodological defects. Four trials, involving 442 patients, testing mechanical pumping devices were also methodologically flawed, and so pooled results need to be viewed cautiously. Mechanical pumping devices may protect against DVT (12/202 (6%) versus 42/212 (19%); Peto odds ratio 0.24; 95% confidence interval 0.13 to 0.44). Although the limited data indicated a potential benefit, they were inadequate to establish any effect on the incidence of pulmonary embolism and overall mortality. Problems with skin abrasion and compliance were reported. REVIEWER'S CONCLUSIONS: U and LMW heparins protect against lower limb DVT. There is insufficient evidence to confirm either protection against pulmonary embolism or overall benefit, or to distinguish between various applications of heparin. Foot and calf pumping devices appear to prevent DVT, may protect against pulmonary embolism, and reduce mortality, but compliance remains a problem. Good quality trials of mechanical methods as well as direct comparisons with heparin should be considered.

Anticoagulants↗

Concordance of four methods of disability assessment using performance in the home as the criterion method.

OBJECTIVE: To determine the concordance of 4 methods of disability assessment with the criterion method. Performance testing in the home was selected as the criterion. METHODS: The task performance of 57 community-dwelling older women (>/=70 years) with knee osteoarthritis was examined through self report, proxy report, clinical judgment based on impairment measures, performance testing in an occupational therapy clinic, and performance testing in participants' homes. The 26 tasks represented 4 domains of daily living activities: 5 functional mobility, 3 personal care, 14 cognitively oriented instrumental activities of daily living (IADL), and 4 physically oriented IADL. RESULTS: In general, self reports and proxy reports had the highest concordance with in-home performance test results. Nonetheless, even for these methods, depending on task domain, the rate of discordance ranged from 31% to 54%, being least in personal care and greatest in the physically oriented IADL. CONCLUSION: Disability estimates based on self reports, proxy reports, clinical judgments, and hospital performance-based assessments are not interchangeable with in-home task performance.

Activities of Daily Living↗

New Fourier transform infrared based computational method for peptide secondary structure determination. I. Description of method.

Fourier transform infrared (FTIR) experiments in dimethylsulfoxide, a solvent incapable of H donation, demonstrate that H --> D isotopic replacement on the amide side of peptide bonds involves modifications of both the position and intensity of the amide I band. The effect of the isotopic substitution is particularly significant in the 1710-1670 and 1670-1650 cm(-1) regions, which are generally associated with beta-turns and alpha-helices. This behavior, attributed to the existence of intramolecular H-bonds in the polypeptide chain, is directly correlated to the presence of different secondary structures. Utilizing the effects induced by isotopic substitution, a method for the quantitative determination of the percentage of intramolecular H-bonds and the correlated secondary structures is proposed. The method consists of three principal steps: resolution of the fine structure of the amide I band with the determination of the number and position of the different components; reconstruction of the experimentally measured amide I band as a combination of Gaussian and Lorentzian functions, centered on the wave numbers set by band-narrowing methods, through a curve-fitting program; and quantitative determination of the population of the H-bonded carbonyls and the correlated secondary structures by comparison of the integrated intensities pertaining to the components with homologous wave numbers before and after isotopic exchange. The method is tested on a synthetic fragment of proocytocin that was previously analyzed by NMR techniques using the same solvent systems.

Deuterium↗

Quantification of mitral regurgitation--comparison of the proximal flow convergence method and the jet area method.

A total of 92 patients with mitral regurgitation (age 63 +/- 13 years, 51 men, 41 women), quantified by angiography, were studied using color-flow Doppler imaging of isovelocity surface areas in the flow convergence region proximal to the regurgitant orifice (PISAs) and of the regurgitant jet in the left atrium. The PISA radii for the flow velocities (aliasing borders) of 28 and 41 cm/s, jet area, jet length, and relation of jet area to left atrial area were measured. A proximal flow convergence region was imaged in 98% (85%) of all patients for a flow velocity of 28 (41) cm/s. A regurgitant jet could be visualized in all patients. The PISA radii for both flow velocities correlated more closely with the angiographic grade (rSp = 0.79 for both flow velocities) than the jet area (rSp = 0.43), jet length (rSp = 0.39), and relation of jet area to left atrial area (rSp = 0.37). A correct differentiation of grade I-II from grade III-IV mitral regurgitation was provided in 95% of the patients by the proximal flow convergence method for both flow velocities and in up to 78% of the patients by the jet area method using the uncorrected jet area. The PISA radii correlated weakly with the parameters from the regurgitant jet (r = 0.5-0.58). It can be concluded that the proximal flow convergence method and the jet area method reach comparable sensitivity for the detection of mitral regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Searching for a better willingness to pay elicitation method in rural Nigeria: the binary question with follow-up method versus the bidding game technique.

OBJECTIVES: To compare the theoretical validity and predictive validity of the binary with follow-up questions technique and the bidding game, using hypothetical and actual WTP for insecticide-treated nets (ITNs) in Nigeria. METHODS: Each elicitation method was applied in one of two rural communities in Enugu state, Nigeria. A pre-tested interviewer-administered questionnaire was administered to household heads or representatives of households. WTP was elicited in each after presenting the scenario and showing a sample of the ITNs to the respondents. Then, within an interval of 1-2 months, the nets were sold to the respondents to compare hypothetical and actual WTP. FINDINGS: Consistent slightly higher mean and median WTP amounts were elicited from Mbano where the bidding game was used. The WTP technique was able to predict WTP responses correctly in 75% and 85% of cases in Orba and Mbano, respectively. Chi-square analysis did not show any statistical difference in values from both communities (p>0.05). CONCLUSION: Though the two techniques yielded similar results, the thrust should be the development of a WTP elicitation method that best mimics the bargaining process in normal market situations in rural Nigeria. Such an indigenous technique will help improve the predictive validity of the contingent valuation method.

Adult↗

A new method of dissolution in vitro, the "Bio-Dis" apparatus: comparison with the rotating bottle method and in vitro: in vivo correlations.

The aim was to study a new method of dissolution in vitro, the "Bio-Dis" apparatus, and to compare it with the classical rotating bottle method. Several theophylline controlled-release drug dosage forms were studied. Dissolution testing was performed in increasing pH in standard conditions and after treatment with peanut oil in order to simulate high fat meals and to correlate the in vitro percent dissolved with the in vivo results obtained. The in vivo study was carried out on three groups of healthy volunteers receiving each dosage form in a randomized order just before a high fat breakfast or in the fasting state. The in vitro percent dissolved obtained was compared with those published results obtained with rotating bottles. A linear relationship was established between these results. From the in vivo absorbed percentages calculated according to the Wagner-Nelson method, a linear relation was found between the in vivo percent absorbed and the in vitro percent dissolved in the different conditions. The relationships observed are similar for all the forms under both conditions. The "Bio-Dis" offers advantages over the rotating bottle method. The study reported allows this dissolution apparatus to be proposed as an alternative to the rotating bottle apparatus.

Biological Availability↗

Noninvasive, real-time method for the examination of thymidine uptake events--application of the method to V-79 cell synchrony studies.

[14C]Thymidine uptake into V-79 hamster lung fibroblasts has been successfully demonstrated using a noninvasive, real-time method utilizing Cytostar-T scintillating microplates. These plates are standard format, tissue culture-treated, 96-well microplates with an integral scintillating base. The microplates permit the culture and observation of adherent cell monolayers. Biological activities of the cells can be studied by the provision of specific radiolabeled compounds. The biological activities of the adherent monolayer bring the specific radiolabel into proximity with the scintillating base and a scintillation signal is thereby generated. [14C]Thymidine incorporation on the microplates can be used to examine cell proliferation and cell cycle events. Using a combined mitotic shake-off/aphidicolin treatment to achieve synchronization, the thymidine incorporation activities of V-79 cells have been examined on Cytostar-T plates and correlated to traditional methods of determining incorporation. The method was further used to examine the effects of colcemid and olomoucine, both chemical inhibitors of cell proliferation, on synchronous populations of cells. The homogeneous detection format and the microplate nature of the method suggest a role for scintillating microplates in cell biology research and drug discovery.

Animals↗

An improved fluorometric high-performance liquid chromatography method for sialic acid determination: an internal standard method and its application to sialic acid analysis of human apolipoprotein E.

An improved fluorometric HPLC method for sialic acid determination was developed by employing synthetic N-propionylneuraminic acid (NPNA) as an internal standard. A fixed amount of NPNA was added to a sialoglycoconjugate sample. After hydrolyzing sialioglycoconjugates with diluted sulfuric acid, the released sialic acids and NPNA were derivatized with a fluorogenic compound, 1,2-diamino-4,5-(methylenedioxy)benzene (DMB), followed by fluorometric HPLC. The fluorescent derivative of NPNA was separated from those of N-acetylneuraminic acid, N-glycolylneuraminic acid, 2-keto-3-deoxy-D-glycero-D-galacto-nonoic acid, and 2-keto-3-deoxyoctanoate on HPLC. The separation of NPNA derivative on HPLC was not interfered by components of biological samples such as human sera. Using this internal standard method, low amounts of NANA (0.15-1.0 ng) were quantified with the coefficient of variation values below 4%. Using this method, the sialic acid content of human apolipoprotein E was successfully determined. The present method is useful for sensitive and accurate quantification of sialic acids of different molecular species in biological samples.

Apolipoproteins E↗

A novel method for production of monoclonal antibodies. Evaluation and expectation of the rat lymph node method in cell and molecular biology.

A newly developed method using rat lymph nodes provided us with substantial amounts of high quality monoclonal antibodies. The method has characteristic features, a single injection of an emulsified antigen via the rat's hind footpads is sufficient for immunization. Enlarged medial iliac lymph nodes can be used for cell fusion to produce hybridomas 2 weeks and later after the antigen injection. The production frequency of target hybridomas is about 10 times higher than that of a conventional spleen method. Our current knowledge about the production of monoclonal antipeptide antibodies and monoclonal nephritogenic autoantibodies by the method is described.

Amino Acid Sequence↗

Multiple Parameter Estimation in an Adaptive Psychometric Method: MUEST, an Extension of the QUEST Method

An extension of the so-called QUEST method of Watson and Pelli (1979, 1983) is proposed. In contrast to the traditional QUEST method, the new method, the MUEST method, offers the possibility of simultaneously estimating more than one parameter of a parametric representation of the psychometric function. Knowledge about more parameters gives a higher guarantee of obtaining correct threshold values. The basic extension itself is analytically quite modest and can be explained in a few sentences. However, the involved additional techniques, like the placing of stimulus levels, require a more extensive description, which is presented here. Copyright 1997 Academic Press. Copyright 1997 Academic Press

Journal Article↗

Sulfamethizole capsule method. A new method for assessing gastric emptying of solids.

We have developed a new method that is capable of assessing gastric emptying in humans. This method is based on the rapid absorption of sulfamethizole in the upper small intestine. Sulfamethizole capsules are gelatin capsules that are filled with a solid composed of egg albumin and sulfamethizole. After subjects ingested of 15 capsules with ham and bread, blood concentrations of sulfamethizole were measured and the areas under the sulfamethizole concentration-time curve (AUC) were calculated as an index of gastric emptying. After ingestion of 99mTc-labeled sulfamethizole capsules, there was a statistically significant correlation between the percentage of radioactivity remaining in the stomach at 120 min and AUC for 120 min (r = -0.82, P < 0.01). This method yielded a reliable value for gastric emptying of a solid meal as estimated by AUC. This method can be considered safe and is easily applicable to human subjects for assessment of gastric emptying.

Adult↗

A gel filtration high-performance liquid chromatographic method for determination of hepatic and renal metallothionein of rat and in comparison with the cadmium-saturation method.

Metallothionein (MT) is a low-mol-wt protein. The essential trace elements copper and zinc and the potentially toxic elements, such as cadmium, can induce the synthesis of and bind to MT. The major functions of MT are related to metal metabolism. This paper reported and evaluated a new method for determination of hepatic and renal MT of rat by using high performance liquid chromatography (HPLC) with a Superdex 75 gel filtration column. The tissue was homogenized and centrifuged, then the supernatant was pretreated simply by cadmium saturation and heating before HPLC determination. The MT was completely and clearly separated from other proteins in the rat tissues in a short time, and was quantitated directly as a function of UV absorbance at 250 nm. The recovery both for hepatic and renal MT of rat were exceed 90%. The coefficient of variation was 1.3% for hepatic MT of rat and 1.7% for renal MT of rat. The detection limit was 0.265 microgram for hepatic MT and 0.095 microgram for renal MT of rat. The present method was compared with the traditional cadmium-saturation method for determination of hepatic and renal MT of rat. A good correlation was found in these two methods.

Animals↗

Long-term results of aortic valve translocation for mycotic periannular abscess: comparative study of Danielson's original method and our threadless method.

Between June, 1983, and October, 1992, we performed Danielson's original translocation method in four patients (group I) and our translocation method in seven patients (group II), for the treatment of active periannular abscess. There were no perioperative or hospital deaths in either group. The long-term results of these two groups are compared in this report. There were four late deaths (mortality rate 100%) in group I, and three late deaths (mortality rate 43%) in group II. The causes of death were cardiac in six patients and noncardiac in one patient. Vein graft failure occurred in one group I patient (25%) and in two group II patients (28%). Rupture or aortic pseudoaneurysm formation occurred in three group I patients (75%). These findings suggest that our threadless method may be superior to Danielson's original translocation method. Therefore, with close observation, especially of saphenons vein great (SVG) failure, arterial graft use could be acceptable for translocation.

Abscess↗

A coulometric method for determining substances that interfere with the measurement of water in oils and other chemicals by the Karl Fischer method.

In order to fulfill a need to measure water in crude oils containing materials that interfere with the measurement of water by the Karl Fischer method, by reacting with iodine or iodide, a coulometric method has been developed and validated using 0.1 mol L(-1) Sodium thiosulfate as a calibrant. These interfering substances were measured in water-mass-equivalents, which were expressed as the mass of water that reacts with an equal mass of iodine in the Karl Fischer method. The SO(2)-free reagent that has been modified reacts quantitatively with sodium thiosulfate, cysteine and ascorbic acid but does not react with vinyl acetate. The level of interfering substances was measured in five transformer oils (including Reference Materials RM 8506 and RM 8507), a high and a low sulfur crude oil (Standard Reference Materials SRM 2721 and SRM 2722 respectively), a white oil, a high-vacuum oil and a high-viscosity base-stock oil. One oil contained less than 10 mg kg(-1) (water-mass-equivalents of interfering substances in oil) and two oils (RM 8507 and Drakeol 35) contained no measurable amount of interfering material (<0.2 mg kg(-1)). SRM 2271, a sour crude oil contained 834 mg kg(-1) (standard deviation (SD)=25 mg kg(-1)) (water-mass-equivalents of interfering substances in oil). Approximately 20% of this material was volatile and an additional 20% appeared to undergo some degradation (possibly oxidation) once the oil was exposed to air. These results indicate that this is a general method for measuring substances in oils that react with iodine and that it is capable of measuring in a variety of oils, using commercial instrumentation, interfering substances that inflate water measurements.

Journal Article↗

Isotope-dilution ICP-MS for trace element determination and speciation: from a reference method to a routine method?

This critical review discusses the conditions under which inductively coupled plasma-isotope dilution mass spectrometry (ICP-IDMS) is suitable as a routine method for trace element and element-speciation analysis. It can, in general, be concluded that ICP-IDMS has high potential for routine analysis of trace elements if the accuracy of results is of predominant analytical importance. Hyphenated techniques with ICP-IDMS suffer both from lack of commercially available isotope-labeled spike compounds for species-specific isotope dilution and from the more complicated system set-up required for species-unspecific ICP-IDMS analysis. Coupling of gas or liquid chromatography with species-specific ICP-IDMS, however, enables validation of analytical methods involving species transformations which cannot easily be performed by other methods. The potential and limitations of ICP-IDMS are demonstrated by recently published results and by some unpublished investigations by our group. It has been shown that possible loss of silicon as volatile SiF4 during decomposition of a sample by use of hydrofluoric acid has no effect on trace silicon determination if the isotope-dilution step occurs during digestion in a closed system. For powder samples, laser ablation ICP-IDMS can be applied with an accuracy comparable with that only available from matrix-matched standardization, whereas the accuracy of electrothermal vaporization ICP-IDMS was strongly dependent on the element determined. The significance of easy synthesis of isotope-labeled spike compounds for species-specific ICP-IDMS is demonstrated for monomethylmercury and Cr(VI). Isotope-exchange reactions between different element species can prevent the successful application of ICP-IDMS, as is shown for iodinated hydrocarbons. It is also shown for monomethylmercury that species transformations during sample-pretreatment steps can be followed by species-specific ICP-IDMS without loss of accuracy. A relatively simple and time-efficient procedure for determination of monomethylmercury in environmental and biological samples is discussed. The method, which entails a rapid microwave-assisted isotope dilution step and in-situ extraction of the derivatized species, has good potential for routine application in the future.

Journal Article↗

Alkaline haematin D-575, a new tool for the determination of haemoglobin as an alternative to the cyanhaemiglobin method. I. Description of the method.

A new method for the rapid and accurate measurement of haemoglobin has been developed as an alternative to the conventional cyanhaemiglobin method. This method is based on the conversion of all haeme, haemoglobin, and haemiglobin species into a stable end product by an alkaline solution of a non-ionic detergent ('AHD reagent'). The reaction product, designated as alkaline haematin D-575, is extremely stable and shows a characteristic absorption peak at 575 nm. As compared to the cyanhaemiglobin method, the determination of haemoglobin by alkaline haematin D-575 offers several advantages such as (1) extreme stability of the AHD reagent and the conversion product, (2) decreased conversion time of all haemoglobin species into the end product, (3) decreased amounts of plasma and cell errors, and errors caused by delayed conversion of carboxy- and fetal haemoglobins, and (4) standardisation by a primary standard (purified crystalline chlorohaemin).

Heme↗