OPERATIONS ON THE MIDDLE EAR AND MASTOID—Changing Aspects of Treatment in Chronic Active Disease

From 1953 to 1957, inclusive, 373 patients were operated on for chronic mastoid disease at the Mayo Clinic. Mainly because of the extensive use of magnifying glasses and microscopes, through these years, closer attention has been given to the preservation or improvement of hearing by meticulous procedures on the structures of the middle ear and the use of skin grafts. It is stressed, however, that it is extremely important to eradicate the underlying disease. Illustrative cases to represent different types of procedures are presented. The author recommends closer attention to the condition of the round window in the future.     

An adaptive single-step FDR procedure with applications to DNA microarray analysis

The use of multiple hypothesis testing procedures has been receiving a lot of attention recently by statisticians in DNA microarray analysis. The traditional FWER controlling procedures are not very useful in this situation since the experiments are exploratory by nature and researchers are more interested in controlling the rate of false positives rather than controlling the probability of making a single erroneous decision. This has led to increased use of FDR (False Discovery Rate) controlling procedures. Genovese and Wasserman proposed a single-step FDR procedure that is an asymptotic approximation to the original Benjamini and Hochberg stepwise procedure. In this paper, we modify the Genovese-Wasserman procedure to force the FDR control closer to the level alpha in the independence setting. Assuming that the data comes from a mixture of two normals, we also propose to make this procedure adaptive by first estimating the parameters using the EM algorithm and then using these estimated parameters into the above modification of the Genovese-Wasserman procedure. We compare this procedure with the original Benjamini-Hochberg and the SAM thresholding procedures. The FDR control and other properties of this adaptive procedure are verified numerically.     

Cervical endometriosis, a case presenting with intractable spotting

Cervix uteri is regarded as an infrequent localization for endometriosis. With widespread use of invasive cervical procedures, however, an increased incidence can be expected. Limited awareness of the clinical appearance of the disease may account for its apparent rarity. This presentation aims to refocus attention to the disease by reviewing the case of a woman who presented to us with minimal metrorrhagia, which is a rare symptom of cervical endometriosis.     

树突状细胞在抗感染免疫研究中的最新进展

树突状细胞(Dendritic cell,DC)是体内功能最强的抗原提呈细胞,也是介导机体固有免疫应答和适应性免疫应答的桥梁,其作用也越来越受到科研工作者的关注,而树突状细胞体外培养技术的发展成熟,为设计和发展DC依赖性疫苗提供了科学依据,也为感染性和肿瘤性疾病的预防和治疗展示了很好的应用前景。因此,对树突状细胞抗感染免疫方面研究的最新进展做一综述。     

A latent class model to multiply impute missing treatment indicators in observational studies when inferences of the treatment effect are made using propensity score matching

Analysts often estimate treatment effects in observational studies using propensity score matching techniques. When there are missing covariate values, analysts can multiply impute the missing data to create m completed data sets. Analysts can then estimate propensity scores on each of the completed data sets, and use these to estimate treatment effects. However, there has been relatively little attention on developing imputation models to deal with the additional problem of missing treatment indicators, perhaps due to the consequences of generating implausible imputations. However, simply ignoring the missing treatment values, akin to a complete case analysis, could also lead to problems when estimating treatment effects. We propose a latent class model to multiply impute missing treatment indicators. We illustrate its performance through simulations and with data taken from a study on determinants of children's cognitive development. This approach is seen to obtain treatment effect estimates closer to the true treatment effect than when employing conventional imputation procedures as well as compared to a complete case analysis.     

Chimpanzees in hepatitis C virus research: 1998–2007

Background  Chimpanzees have been widely used in hepatitis C virus (HCV) research, but their endangered status and high financial and ethical costs have prompted a closer review.
Methods  One hundred and nine articles published in 1998–2007 were analyzed for the number of chimpanzees involved, experimental procedures, objectives and other relevant issues.
Results  The articles described the use of 852 chimpanzees, but accounting for likely multiple uses, the number of individual chimpanzees involved here is estimated to be approximately 500. Most articles addressed immunology and inoculation studies. A significant portion of studies lasted for several months or years. Approximately one half of the individual chimpanzees were each used in 2–10 studies.
Conclusions  Significant financial and scientific resources have been expended in these chimpanzee HCV studies. Discussion addresses troublesome questions presented by some of the reviewed articles, including statistical validity, repeatability, and biological relevance of this model. These concerns merit attention as future approaches to HCV research and research priorities are considered.     

Thrombotic complication during intracoronary imaging

Intracoronary imaging with intracoronary ultrasound and coherence tomography is often used in the follow-up of coronary stent implantation. The present case shows an infrequent complication of these procedures, suggesting our continued attention to the selective use of these invasive procedures.     

From helix-coil transitions to protein folding

An evolution of procedures to simulate protein structure and folding pathways is described. From an initial focus on the helix-coil transition and on hydrogen-bonding and hydrophobic interactions, our original attempts to determine protein structure and folding pathways were based on an experimental approach. Experiments on the oxidative folding of reduced bovine pancreatic ribonuclease A (RNase A) led to a mechanism by which the molecule folded to the native structure by a minimum of four different pathways. The experiments with RNase A were followed by development of a molecular mechanics approach, first, making use of global optimization procedures and then with molecular dynamics (MD), evolving from an all-atom to a united-residue model. This hierarchical MD approach facilitated probing of the folding trajectory to longer time scales than with all-atom MD, and hence led to the determination of complete folding trajectories, thus far for a protein containing as many as 75 amino acid residues. With increasing refinement of the computational procedures, the computed results are coming closer to experimental observations, providing an understanding as to how physics directs the folding process.     

Cardiovascular disease in systemic lupus erythematosus: has the time for action come?

PURPOSE OF REVIEW: The recognition that inflammation is a hallmark of atherosclerotic disease has led to a series of studies reporting accelerated atherogenesis in chronic inflammatory diseases. Indeed, systemic lupus erythematosus is associated with an increased incidence of cardiovascular disease and the etiology thereof deserves closer attention. RECENT FINDINGS: The association between systemic lupus erythematosus and accelerated atherosclerosis has recently been confirmed by surrogate-marker studies for cardiovascular disease in patients with systemic lupus erythematosus. Since the propensity towards cardiovascular disease cannot solely be explained by classical risk factors, disease-specific pathways have been put forward as additional risk factors. SUMMARY: In the present review, we will discuss several of these factors as well as their potential impact for future prevention strategies in systemic lupus erythematosus.     

REDUCING GONAD IRRADIATION IN PEDIATRIC DIAGNOSIS

The greatest danger of carcinogenesis and of genetic damage through diagnostic radiologic procedures is in children, whose smaller bodies are more vulnerable and who have a longer life span in which this damage can be realized.Film badges placed on the gonad area during radiologic studies indicated widely varying degrees of gonad irradiation from similar procedures. These results emphasize the importance of technique in protecting children from unnecessary exposure. Such exposure can be reduced by greater beam filtration, use of higher tube potentials, careful beam collimation and centering, closer coning and shielding of the gonads. A new film tested reduced exposure time by 50 per cent. Further reduction was obtained by high-speed screens.A most important measure is avoidance of unnecessary, repetitious and undiagnostic studies.Fluoroscopy should be avoided if possible. If not, the operator must dark-adapt his eyes, use the smallest possible current, the narrowest beam, and the shortest exposure time. Image intensification promotes these aims.Modern equipment, properly shielded, assures against unsuspected exposure.     

Life After Death: Are Autophagy Genes Involved in Cell Death and Survival During Plant Innate Immune Responses?

It has not escaped the attention of the plant disease resistance community that the vacuole is rapidly emerging as a central player in the execution of cell death. On the one hand the targeted destruction of the vacuole—from the inside out—by vacuolar processing enzymes (VPE) is required to induce PCD in pathogen-infected cells. On the other hand, an intact vacuole is vital for a functional autophagic response to ensure survival of uninfected cells. At face value, the two responses seem to represent distinct resistance mechanisms that operate at divergent branch points and their use of the vacuole merely coincidental. However, closer examination has led us to propose an interesting hypothesis that accounts for these two opposing roles of the vacuole in both VPE-mediated PCD and autophagy-dependent cell survival. During initial infection, we propose a mechanism similar to the CPY transport pathway in yeast wherein select ATG genes are needed for VPE transport, vacuolar processing and initiation of PCD. Later during infection, autophagy-specific genes are needed for autophagosome formation, sequestration of VPE preproteins and VPE degradation.     

Advances in retroviral transduction of hematopoietic stem cells for the gene therapy of atherosclerosis

PURPOSE OF REVIEW: Atherosclerosis is a chronic inflammatory disease that is the primary cause of morbidity and mortality in the developed world. Many studies have shown that macrophages and T-cells play critical roles in multiple aspects of the pathogenesis of the disease. Given that these cells are ultimately derived from bone marrow precursors, the concept of performing gene therapy for atherosclerosis through the retroviral transduction of hematopoietic stem cells has received much attention. This review will highlight recent advances that will help bring this goal closer. RECENT FINDINGS: The clinical application of retroviral gene transfer into hematopoietic stem cells has been hampered, in part, by the absence of vectors that can direct long-lasting, cell-type specific gene expression. In this review we will detail recent developments in the design of novel retroviral and lentiviral vectors that appear to overcome these problems, offering approaches to express therapeutic genes in specific cell-types within atherosclerotic lesions. We will also highlight advances in our understanding of the pathogenesis of atherosclerosis that may offer new gene therapeutic targets. SUMMARY: The use of retroviral transduction of hematopoietic stem cells for treatment of patients with atherosclerosis still remains a long-term goal. However, the recent development of retroviral vectors capable of directing expression to specific cell types within the lesion will allow more targeted therapeutic strategies to be devised. In addition, these vectors will provide powerful experimental tools to further our understanding of the pathogenesis of the disease.     

Cutaneous streptothricosis in a mule

The first case of dermatophilosis in a mule is reported at São Paulo (Brazil). The animal presented a single crusty lesion on its face. Direct and cultural examinations were carried out and the parasite was identified asD. congolensis. As the number of cases reported in equidae is very small, attention is called to appropriate laboratory diagnostic procedures, which will undoubtedly demonstrate a wider prevalence of the disease.     

Ceramic Classification in Middle Missouri Prehistory

Abstract

Consideration is given the procedures, utility, and problems of ceramic classification used in Middle Missouri prehistory. A review of the development of the ware-type concepts and theoretical approaches to ceramic typologies are provided. Special attention is given the problems inherent in most of the ware and type definitions in the literature. An evaluation is made of the extant reports which use ceramics in unique or different ways, and suggestions are provided concerning potential productive analytical procedures.     

Towards high throughput metabolic flux analysis in plants

Research on plant metabolism is currently experiencing the common use of various omics methods creating valuable information on the concentrations of the cell's constituents. However, little is known about in vivo reaction rates, which can be determined by Metabolic Flux Analysis (MFA), a combination of isotope labeling experiments and computer modeling of the metabolic network. Large-scale applications of this method so far have been hampered by tedious procedures of tissue culture, analytics, modeling and simulation. By streamlining the workflow of MFA, the throughput of the method could be significantly increased. We propose strategies for these improvements on various sub-steps which will move flux analysis to the medium-throughput range and closer to established methods such as metabolite profiling. Furthermore, this may enable novel applications of MFA, for example screening plant populations for traits related to the flux phenotype.     

Life after death: are autophagy genes involved in cell death and survival during plant innate immune responses?

It has not escaped the attention of the plant disease resistance community that the vacuole is rapidly emerging as a central player in the execution of cell death. On the one hand the targeted destruction of the vacuole-from the inside out-by vacuolar processing enzymes (VPE) is required to induce PCD in pathogen-infected cells. On the other hand, an intact vacuole is vital for a functional autophagic response to ensure survival of uninfected cells. At face value, the two responses seem to represent distinct resistance mechanisms that operate at divergent branch points and their use of the vacuole merely coincidental. However, closer examination has led us to propose an interesting hypothesis that accounts for these two opposing roles of the vacuole in both VPE-mediated PCD and autophagydependent cell survival. During initial infection, we propose a mechanism similar to the CPY transport pathway in yeast wherein a select set of genes, including several which encode a phosphatidylinositol 3-kinase complex that is needed for autophagy, are needed for VPE transport, vacuolar processing and initiation of PCD. Later during infection, autophagyspecific genes are needed for autophagosome formation, sequestration of VPE preproteins and VPE degradation.     

Controlled group designs in biofeedback research: Ask, “what does the control group control for?”

The extant literature on the specific role of biofeedback in promoting skeletal muscular relaxation is reviewed and found deficient with respect to the use of properly controlled group outcome research. The review emphasizes the failure of commonly used control procedures to adequately control a number of potentially confounding variables. Strengths and weaknesses of three types of controlled group design (attention placebo, pseudofeedback, and altered contingency) are discussed with respect to their relative usefulness in controlling certain nonspecific or placebo effects in biofeedback research. Many published biofeedback studies failed to measure the credibility of control procedures or the subject's ability to discriminate different feedback contingencies. The studies reviewed suggest that the various control procedures used are not inert and are not equivalent with respect to their effects on control group behavior. The suggestion is made that the controlled group outcome design be accepted as the minimum requirement for testing the specific effects of biofeedback, and possible methods for improving control procedures are discussed.     

'Beyond being': emergent narratives of suffering in Vietnam

Intertwining ethnographic and literary accounts, this article explores the mutual relationship between suffering and agency. The article describes how young Vietnamese women use narrative to find meaning in the suffering that a late-term abortion causes. Seeking to further develop anthropological use of the concept of social suffering, the article argues that existing scholarship has tended to neglect the importance of human agency and imagination, hinging as it does on suffering as entrenched within structural forces. The article contends that this neglect must be understood in the context of the particular epistemological and ethical conditions under which anthropological studies of human suffering are produced, and that closer attention to the human engagements out of which ethnographic accounts are fashioned may bring into analysis not only the harm that social forces can inflict on people, but also their capacities for action and imagination.     

Chickenpox in Canada, 1924-87.

Because of the lack of an effective vaccine and the difficulty in implementing any effective control measures, physicians and public health practitioners have paid little attention to understanding the epidemiologic features of chickenpox. No data on the incidence rate in Canada are available for 1959-85. However, Ontario data suggest an overall decrease in the annual rate during the 1960s and a stable rate since the mid-1970s. High incidence rates are expected among children 5 to 9 years of age because of their susceptibility and their greater exposure in school. Low incidence rates among older age groups are expected, because most of these people have already been exposed to the virus. The disease is more serious among infants than among other children. The risk of death from chickenpox is also highest among infants. More patient-specific information and improved collection of incidence data are required to measure any impact from future control procedures, including the use of vaccines currently being developed.