Histochemistry of carbohydrates as performed by physical development procedures

Summary The histochemistry of carbohydrates demonstrated by means of physical development procedures has been reviewed in terms of the use and reliability of the procedures, physical developers, practice of the procedures, a fundamental series of light and electron microscopic methods and certain other promising aspects of this area of histochemistry. A line of fundamental light- and electron-microscopic histochemical methods for carbohydrates using physical development procedures such as periodic acid thiocarbohydrazide-silver protein-physical development (PA-TCH-SP-PD), high- or low-iron diamine (HID or LID)-TCH-SP-PD and lectin-gold (LT-G)-PD and related methods has been found to be more efficient, compared with those without physical development procedures. Since a series of other promising histochemical methods for carbohydrates using physical development procedures have been derived or are now being introduced, these procedures could be regarded as an unusually potent vehicle for effectively advancing carbohydrate histochemistry in both light and electron microscopy.     

Stopping rules in Bayesian adaptive threshold estimation

Threshold estimation with sequential procedures is justifiable on the surmise that the index used in the so-called dynamic stopping rule has diagnostic value for identifying when an accurate estimate has been obtained. The performance of five types of Bayesian sequential procedure was compared here to that of an analogous fixed-length procedure. Indices for use in sequential procedures were: (1) the width of the Bayesian probability interval, (2) the posterior standard deviation, (3) the absolute change, (4) the average change, and (5) the number of sign fluctuations. A simulation study was carried out to evaluate which index renders estimates with less bias and smaller standard error at lower cost (i.e. lower average number of trials to completion), in both yes-no and two-alternative forced-choice (2AFC) tasks. We also considered the effect of the form and parameters of the psychometric function and its similarity with the model function assumed in the procedure. Our results show that sequential procedures do not outperform fixed-length procedures in yes-no tasks. However, in 2AFC tasks, sequential procedures not based on sign fluctuations all yield minimally better estimates than fixed-length procedures, although most of the improvement occurs with short runs that render undependable estimates and the differences vanish when the procedures run for a number of trials (around 70) that ensures dependability. Thus, none of the indices considered here (some of which are widespread) has the diagnostic value that would justify its use. In addition, difficulties of implementation make sequential procedures unfit as alternatives to fixed-length procedures.     

Maximizing the use of the abdominoplasty incision

Candidates for abdominoplasty often request multiple procedures at the time of consultation. Some of these patients have the potential opportunity to have ancillary procedures performed through the abdominoplasty incision, such as breast augmentation or suction-assisted lipectomy. Access via the abdominoplasty incision can also limit the need for distant donor sites, for instance, when autologous fillers or rib graft are necessary. The techniques described are straightforward and are based on standard principles that should be considered when ancillary procedures are performed in conjunction with abdominal contouring procedures. In a review of 70 consecutive patients undergoing abdominoplasty, 91 ancillary procedures were performed in conjunction with the abdominoplasty. Of the total number of patients undergoing abdominoplasty, 29 patients underwent 30 procedures facilitated through their abdominoplasty incision, including 23 suction-assisted lipectomies of the flanks, six breast augmentations, and one rib cartilage harvesting for rhinoplasty. A review of the author's experience and discussion for potential options afforded by this exposure are presented.     

Exact Tests for Comparing Two Paired Proportions with Incomplete Data

Various asymptotic test procedures have been developed previously for testing the equality of two binomial proportions with partially incomplete paired data. Test procedures that discard incomplete observations have been shown to be less powerful than those procedures that utilize all available observations. On the other hand, asymptotic test procedures that utilize all available observations may not be reliable in small‐sample problems or sparse data structures. In this article, unconditional exact test procedures are proposed for testing the equality of two paired binomial proportions with partially incomplete paired data under a random mechanism. The proposed unconditional exact test methods are illustrated with real data from a neurological study. Empirical studies are conducted to investigate the performance of these and other test procedures with respect to size and power. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Multiple testing in candidate gene situations: a comparison of classical, discrete, and resampling-based procedures

In candidate gene association studies, usually several elementary hypotheses are tested simultaneously using one particular set of data. The data normally consist of partly correlated SNP information. Every SNP can be tested for association with the disease, e.g., using the Cochran-Armitage test for trend. To account for the multiplicity of the test situation, different types of multiple testing procedures have been proposed. The question arises whether procedures taking into account the discreteness of the situation show a benefit especially in case of correlated data. We empirically evaluate several different multiple testing procedures via simulation studies using simulated correlated SNP data. We analyze FDR and FWER controlling procedures, special procedures for discrete situations, and the minP-resampling-based procedure. Within the simulation study, we examine a broad range of different gene data scenarios. We show that the main difference in the varying performance of the procedures is due to sample size. In small sample size scenarios,the minP-resampling procedure though controlling the stricter FWER even had more power than the classical FDR controlling procedures. In contrast, FDR controlling procedures led to more rejections in higher sample size scenarios.     

Development of gatekeeping strategies in confirmatory clinical trials

This paper discusses multiplicity issues arising in confirmatory clinical trials with hierarchically ordered multiple objectives. In order to protect the overall type I error rate, multiple objectives are analyzed using multiple testing procedures. When the objectives are ordered and grouped in multiple families (e.g. families of primary and secondary endpoints), gatekeeping procedures are employed to account for this hierarchical structure. We discuss considerations arising in the process of building gatekeeping procedures, including proper use of relevant trial-specific information and criteria for selecting gatekeeping procedures. The methods and principles discussed in this paper are illustrated using a clinical trial in patients with type II diabetes mellitus.     

Psychiatric Treatment: General Implications and Lessons From Recent Court Decisions in California

The California legislature enacted tight constraints on the use of psychosurgery and electroconvulsive therapy in 1974. In April 1976 a State Court of Appeals declared part of the law to be unconstitutional. In doing so, the court enunciated several principles for regulating medical procedures. It affirmed the inherent police powers which permit the state to safeguard the public, especially incompetent, involuntary or confined persons, with respect to intrusive and hazardous medical procedures and to procedures which affect thought or feeling. Although limited to legislation concerning two psychiatric procedures, the court''s decision, and subsequently enacted legislation governing these procedures, has implications for other medical procedures and for other parts of the nation.     

Fluorescent Staining Technique for Nucleoid Regions of Streptosporangium albidum and Streptosporangium brasiliense

Fluorescent staining procedures were developed for elucidating the nucleoid region in Streptosporangium albidum and Streptosporangium brasiliense. In these procedures, plugs of nutrient agar were inoculated with the microorganims and then covered with a sterile glass slide. The growing cells adhered to the surface of the slide and remained attached throughout the staining procedures. Two separate staining methods were utilized, one with bisbenzimid H33258 and the other with auramine O. Fluorescent microscopy revealed intensely stained nucleoid regions within mycelia, spores, and sporangia.     

Testing equality of survival functions based on both paired and unpaired censored data

We introduce two test procedures for comparing two survival distributions on the basis of randomly right-censored data consisting of both paired and unpaired observations. Our procedures are based on generalizations of a pooled rank test statistic previously proposed for uncensored data. One generalization adapts the Prentice-Wilcoxon score, while the other adapts the Akritas score. The use of these particular scoring systems in pooled rank tests with randomly right-censored paired data has been advocated by several researchers. Our test procedures utilize the permutation distributions of the test statistics based on a novel manner of permuting the scores. Permutation versions of tests for right-censored paired data and for two independent right-censored samples that use the proposed scoring systems are obtained as special cases of our test procedures. Simulation results show that our test procedures have high power for detecting scale and location shifts in exponential and log-logistic distributions for the survival times. We also demonstrate the advantages of our test procedures in terms of utilizing randomly occurring unpaired observations that are discarded in test procedures for paired data. The tests are applied to skin graft data previously reported elsewhere.     

The role of a commercial radiation dose index monitoring system in establishing local dose reference levels for fluoroscopically guided invasive cardiac procedures

PurposeThe primary goal was to evaluate local dose level for fluoroscopically guided invasive cardiac procedures in a high-volume activity catheterization laboratory, using automatic data registration with minimal impact on operator workload. The secondary goal was to highlight the relationship between dose indices and acquisition parameters, in order to establish an effective strategy for protocols optimization.MethodsFrom September 2016 to December 2018, a dosimetric survey was conducted in the 2 rooms of the catheterization laboratory of our institution. Data collection burden was minimized using a commercial Radiation Dose Index Monitoring System (RDIMs) that analyzes dicom files automatically sent by the x-ray equipment. Data were combined with clinical information extracted from the HIS records reported by the interventional cardiologist. Local dose levels were established for different invasive cardiac procedures.ResultsA total of 3029 procedures performed for 2615 patients were analyzed. Median KAP were 21 Gycm² for invasive coronary angiography (ICA) procedures, 61 Gycm² for percutaneous coronary intervention (PCI) procedures, 59 Gycm² for combined (ICA+PCI) procedures, 87 Gycm² for structural heart intervention (TAVI) procedures. A significant dose reduction (51% for ICA procedures and 58% for PCI procedures) was observed when noise reduction acquisition techniques were applied.ConclusionsRDIMs are effective tools in the establishment of local dose level in interventional cardiology, as they mitigate the burden to collect and register extensive dosimetric data and exposure parameters. Systematic review of data support the multi-disciplinary team in the definition of an effective strategy for protocol management and dose optimization.     

Optimization of the Water-Insoluble Procedures for <Emphasis Type="Italic">USP</Emphasis> General Chapter <Emphasis Type="Italic">Residual Solvents</Emphasis> <467>

The water-insoluble procedures in US Pharmacopeia (USP) General Chapter Residual Solvents <467>, which are based on European Pharmacopoeia procedures, were optimized and modified before their inclusion in the chapter to improve their scope, performance, and ruggedness. The optimized procedures use a static headspace introduction system with a gas chromatograph equipped with a flame ionization detector. This article describes some of the key changes made to the USP published procedures, including use of dimethyl sulfoxide (DMSO) or dimethylformamide (DMF) as the solvent, addition of 5 mL of water and 1 mL of sample (dissolved in DMSO or DMF) to the headspace vial, use of a 3:1 GC split ratio, and use of new matrix-matched system suitability solutions. These procedures were verified with two different active pharmaceutical ingredients—hydroxyzine pamoate and prednisone. In the investigation, the more polar material (hydroxyzine pamoate) showed greater recoveries for the optimized procedures when prepared in DMSO. The less polar material (prednisone) typically had greater recoveries in DMF for the optimized procedures. During experimentation, insights into sample preparation, additional types of headspace instrumentation, solvent purity, and other parameters were also gained.     

Effects of cluster sampling on epidemiologic analysis in population-based case-control studies

We consider population-based case-control designs in which controls are selected by one of three cluster sampling plans from the entire population at risk. The effects of cluster sampling on classical epidemiologic procedures are investigated, and appropriately modified procedures are developed. In particular, modified procedures for testing the homogeneity of odds ratios across strata, and for estimating and testing a common odds ratio are presented. Simulations that use the data from the 1970 Health Interview Survey as a population suggest that classical procedures may be fairly robust in the presence of cluster sampling. A more extreme example based on a mixed multinomial model clearly demonstrates that the classical Mantel-Haenszel (1959, Journal of the National Cancer Institute 22, 719-748) and Woolf-Haldane tests of no exposure effect may have sizes exceeding nominal levels and confidence intervals with less than nominal coverage under an alternative hypothesis. Classical estimates of odds ratios may also be biased with non-self-weighting cluster samples. The modified procedures we propose remedy these defects.     

Reducing spatial flaws in oligonucleotide arrays by using neighborhood information

We address the problem of detection and correction of spatial flaws in oligonucleotide microarrays. We present two similar procedures, of which one is intended solely for use with replicates and the other has wider applicability. By constructing a set of replicates, with one realistically flawed, we are able to examine the extent to which our procedures are capable of repairing the flaw. We find that, for this purpose, our procedures are superior to the existing 'Harshlight' procedure.     

Optimal multiple testing and design in clinical trials

A central goal in designing clinical trials is to find the test that maximizes power (or equivalently minimizes required sample size) for finding a false null hypothesis subject to the constraint of type I error. When there is more than one test, such as in clinical trials with multiple endpoints, the issues of optimal design and optimal procedures become more complex. In this paper, we address the question of how such optimal tests should be defined and how they can be found. We review different notions of power and how they relate to study goals, and also consider the requirements of type I error control and the nature of the procedures. This leads us to an explicit optimization problem with objective and constraints that describe its specific desiderata. We present a complete solution for deriving optimal procedures for two hypotheses, which have desired monotonicity properties, and are computationally simple. For some of the optimization formulations this yields optimal procedures that are identical to existing procedures, such as Hommel's procedure or the procedure of Bittman et al. (2009), while for other cases it yields completely novel and more powerful procedures than existing ones. We demonstrate the nature of our novel procedures and their improved power extensively in a simulation and on the APEX study (Cohen et al., 2016).     

Quality Control of Fungal and Viral Biocontrol Agents - Assurance of Product Performance

An essential feature of the production of all microbial control agents is an effective quality control system. Well-defined product specifications with accompanying quality control procedures help to maximize product performance, ensure product safety, standardize manufacturing costs and reduce the risks of supply failure, thus building user confidence. A production system that does not have a quality control system is one whose output is uncontrolled and a lack of thorough quality feedback can result in batches of product with variable concentrations of active agent. This results in products with variable performance leading to control failures by users and serious loss of user confidence. Strict quality control procedures are not only essential for product consistency, but also for safety. Where quality control is inadequate, microbial contamination of the final product is inevitable. In most of such cases this will merely lead to a loss of efficacy due to dilution of the active ingredient by competing microorganisms, but also the potential of producing human pathogens must be ruled out. Recognition of contaminants and quantification of the degree of contamination are therefore important in determining any possible risk to human health. Many low technology production systems in use around the world have minimal or no quality control procedures. This is unacceptable and can damage the reputation of microbial control in addition to possibly posing health risks to those that produce or are exposed to the product. Two case studies from developing countries, are used to illustrate how the lack of quality control procedures can lead to the production of low viability, highly contaminated products with low or negligible concentrations of the active ingredient. However, it is also demonstrated that low technology production systems in developing countries can produce high quality products, provided appropriate quality control procedures are firmly implemented. It must be recognized that quality control procedures can be more complex and technologically demanding than the production procedures themselves, but it is largely on the effectiveness of these control procedures that the long-term acceptability of fungal and viral products depends. This paper details the quality control procedures considered necessary in the mass production of fungi and viruses for use as biocontrol agents, and attempts to suggest reasonable standards that can be achieved by all producers.     

Abdominoplasty combined with other major surgical procedures: safe or sorry?

The clinical records of 563 patients undergoing either abdominoplasty alone or in combination with other major surgical procedures were reviewed in order to determine the relative safety of combined procedures. One-hundred-seventeen patients had abdominoplasty alone; 230 had abdominoplasty with either an intraabdominal or major pelvic procedure with or without an additional major aesthetic procedure; 216 had abdominoplasty with one or more major aesthetic procedures (without intraabdominal or pelvic procedures). The rates of occurrence of major complications, including death, pulmonary embolus, and infection, among the three groups were examined. Also examined were morbidity factors such as length of hospital stay and the need for blood transfusion. In this study, the only risk factor identified in predicting major morbidity, specifically the occurrence of pulmonary embolus, was obesity, not the complexity of the surgical procedure.     

Automation in Staining of Cytologic Specimens

With continuous automatic staining procedures, it is now possible to stain hundreds of cytologic specimens per hour with a minimum of effort, and with reproducible optimum results. Two automatic and continuous polychrome staining procedures for cervical-vaginal specimens, and two automatic and continuous hematoxylin-eosin staining procedures for abrasion biopsies are presented. The continuous and automatic procedures reduce the number of solutions and the number of procedural steps needed for cytologic staining. They are simpler, less time-consuming, less costly and give fewer chances for error. They assure reproducible staining results even with less experienced technicians. They permit the technician to be occupied with other activities while the greater part of the staining is being done. They require only the part-time use of the Autotechnicon. They permit variation in staining intensity and color differentiation to suit individual preferences. Their use may be of critical importance in the development of effective electronic screening.     

Comparison of Two Methods for Enumeration of Anaerobe Numbers on Forages and Evaluation of Ethylene Oxide Treatment for Forage Sterilization

Experiments were conducted to (i) compare most-probable-number (MPN) procedures with roll tube procedures for enumeration of forage anaerobic bacteria and (ii) evaluate the efficacy of using ethylene oxide to sterilize wet herbage. Alfalfa, corn, and alfalfa-orchardgrass silages and alfalfa and orchardgrass herbages were analyzed for total anaerobic bacteria (medium pH, 6.8) and acid-tolerant anaerobic bacteria (medium pH, 4.5) by both roll tube and MPN procedures. No difference was found between the roll tube and MPN procedures for total bacteria; however, higher counts were obtained for acid-tolerant bacteria when the MPN procedure was used. Although MPN procedures require less time to obtain an estimate of bacterial numbers, isolation and identification of the microbial population is not possible. Alfalfa herbage was treated with ethylene oxide for 12, 24, or 36 h, incubated for 7 days at 37°C with or without addition of a bacterial inoculant, and analyzed for total bacteria by MPN procedures. Microbial growth after inoculation of ethylene oxide-treated herbage indicated that there was insufficient residual ethylene oxide to inhibit subsequent microbial growth. The results also indicated that 24 h was required to adequately sterilize fresh herbage. Thus, ethylene oxide can be used to sterilize wet herbage for use as a substrate for pure cultures of silage bacteria.     

Randomised Trial Support for Orthopaedic Surgical Procedures

We investigated the proportion of orthopaedic procedures supported by evidence from randomised controlled trials comparing operative procedures to a non-operative alternative. Orthopaedic procedures conducted in 2009, 2010 and 2011 across three metropolitan teaching hospitals were identified, grouped and ranked according to frequency. Searches of the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Database of Systematic Reviews (CDSR) and the Database of Abstracts of Reviews of Effects (DARE) were performed to identify RCTs evaluating the most commonly performed orthopaedic procedures. Included studies were categorised as “supportive” or “not supportive” of operative treatment. A risk of bias analysis was conducted for included studies using the Cochrane Collaboration''s Risk of Bias tool. A total of 9,392 orthopaedic procedures were performed across the index period. 94.6% (8886 procedures) of the total volume, representing the 32 most common operative procedure categories, were used for this analysis. Of the 83 included RCTs, 22.9% (19/83) were classified as supportive of operative intervention. 36.9% (3279/8886) of the total volume of procedures performed were supported by at least one RCT showing surgery to be superior to a non-operative alternative. 19.6% (1743/8886) of the total volume of procedures performed were supported by at least one low risk of bias RCT showing surgery to be superior to a non-operative alternative. The level of RCT support for common orthopaedic procedures compares unfavourably with other fields of medicine.