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PubMed2004

Quantitative imaging through a spectrograph. 1. Principles and theory.

Laser-based optical diagnostics, such as planar laser-induced fluorescence and, especially, Raman imaging, often require selective spectral filtering. We advocate the use of an imaging spectrograph with a broad entrance slit as a spectral filter for two-dimensional imaging. A spectrograph in this mode of operation produces output that is a convolution of the spatial and spectral information that is present in the incident light. We describe an analytical deconvolution procedure, based on Bayesian statistics, that retrieves the spatial information while it avoids excessive noise blowup. The method permits direct imaging through a spectrograph, even under broadband illumination. We introduce the formalism and discuss the underlying assumptions. The performance of the procedure is demonstrated on an artificial but pathological example. In a companion paper [Appl. Opt. 43, 5682-5690 (2004)] the method is applied to the practical case of fuel equivalence ratio Raman imaging in a combustible methane-air mixture.

Journal Article↗

PubMed1988

Epithelial repair versus carcinoma in esophageal brush cytology.

The distinction between repair atypia and carcinoma in esophageal brushings is often difficult. To establish criteria for making this distinction, the cytologic smears from 121 consecutive esophageal brushings and the companion biopsies were reviewed. The most reliable criteria for malignancy included sharply angulated nuclear rims, a high nuclear/cytoplasmic ratio, and coarsely granular chromatin. Nuclei bearing these features were not numerous and had to be carefully sought. Nuclear pleomorphism was a more consistent feature, but it showed considerable overlap with epithelial repair. Cytologic features of multiple nucleoli, macronucleoli, and loss of polarity were common to both repair and carcinoma. Adherence to the criteria established in this study permits the distinction between repair atypia and carcinoma in almost all cases; however, there are lesions of the esophagus with such overlap between the features of repair and carcinoma that it may not be possible to reach a definitive diagnosis. Specific examples, with illustrations, are discussed as diagnostic guides.

Carcinoma, Squamous Cell↗

PubMed1997

Graduates speak: the employment experience of 1995 graduates of diagnostic radiology and radiation oncology training programs.

PURPOSE: To determine the initial employment experience of 1995 graduates of radiology programs. MATERIALS AND METHODS: A questionnaire was mailed to all graduates of radiation oncology programs and to a stratified, random sample of 600 graduates of diagnostic radiology programs. The final response rate was 66%. RESULTS: After graduation, 4%-10% of graduates worked for a period as locum tenens, worked in a job unrelated to radiology, or were unemployed. Immediate postgraduation unemployment was 2%-5%; 7-12 months later, it was less than 0.5%. Median actual salary was approximately equal to median expected salary. Radiation oncology fellowship graduates often had poorer outcomes. Almost half of the graduates with posttraining employment had a job with at least one characteristic regarded as unfavorable by some commentators (most commonly, undesirable location or no opportunity to become a partner), and at least one-fifth had and disliked such a characteristic. Geographic constraints, including the need to find employment for a spouse or companion, did not adversely affect employment outcome. CONCLUSION: Eventual unemployment was low, and starting salaries have not collapsed. Generally, the implications of job characteristics are best assessed by monitoring trends, but the prevalence of non-partnership track employment may well have increased.

Attitude of Health Personnel↗

PubMed1999

Field evaluation of the Determine rapid human immunodeficiency virus diagnostic test in Honduras and the Dominican Republic.

Rapid detection of human immunodeficiency virus (HIV) infection can result in improved patient care and/or faster implementation of public health preventive measures. A new rapid test, Determine (Abbott, Abbott Park, Ill.), detects HIV type 1 (HIV-1) and HIV-2 antibodies within 15 min by using 50 microl of serum or plasma. No specialized equipment or ancillary supplies are required, and results are read visually. A positive result is noted by the appearance of a red line. An operational control (red line) indicates proper test performance. We evaluated the Determine rapid HIV detection test with a group of well-characterized serum samples (CD4 counts and viral loads were known) and serum samples from HIV-positive individuals at field sites in Honduras and the Dominican Republic. In the field evaluations, the results obtained by the Determine assay were compared to those obtained by local in-country HIV screening procedures. We evaluated serum from 100 HIV-positive patients and 66 HIV-negative patients. All samples gave the expected results. In a companion study, 42 HIV-positive samples from a Miami, Fla., serum bank were tested by the Determine assay. The samples had been characterized in terms of CD4 counts and viral loads. Fifteen patients had CD4 counts <200 cells/mm(3), while 27 patients had CD4 counts >200 cells/mm(3). Viral loads ranged from 630 to 873,746 log(10) copies/ml. All samples from the Miami serum bank were positive by the Determine test. Combined results from the multicenter studies indicated that the correct results were obtained by the Determine assay for 100% (142 of 142) of the HIV-positive serum samples and 100% (66 of 66) of the HIV-negative serum samples. The Determine test was simple to perform and the results were easy to interpret. The Determine test provides a valuable new method for the rapid identification of HIV-positive individuals, especially in developing countries with limited laboratory infrastructures.

AIDS Serodiagnosis↗

PubMed2005

What are the odds? Random drug testing of students: a practice perspective.

Companion articles explore random drug testing programs in schools. The first article addresses random drug testing of students from a legal perspective. It describes legal issues and current case law regarding drug testing programs in schools and commonly asked questions regarding these programs. The second article addresses random drug testing of students from a practice perspective. It explores arguments for and against random drug testing programs and the role of the school nurse in policy and procedure development.

Adolescent↗

PubMed2005

What are the odds? Random drug testing of students: a legal perspective.

Adolescent↗

PubMed2006

Robust sequence selection method used to develop the FluChip diagnostic microarray for influenza virus.

DNA microarrays have proven to be powerful tools for gene expression analyses and are becoming increasingly attractive for diagnostic applications, e.g., for virus identification and subtyping. The selection of appropriate sequences for use on a microarray poses a challenge, particularly for highly mutable organisms such as influenza viruses, human immunodeficiency viruses, and hepatitis C viruses. The goal of this work was to develop an efficient method for mining large databases in order to identify regions of conservation in the influenza virus genome. From these regions of conservation, capture and label sequences capable of discriminating between different viral types and subtypes were selected. The salient features of the method were the use of phylogenetic trees for data reduction and the selection of a relatively small number of capture and label sequences capable of identifying a broad spectrum of influenza viruses. A detailed experimental evaluation of the selected sequences is described in a companion paper. The software is freely available under the General Public License at http://www.colorado.edu/chemistry/RGHP/software/.

Computational Biology↗

PubMed2002

[DNA-diagnosis of congenital diseases in companion animals and the role of the practicing veterinarian].

The knowledge on the impact of gene defects on the development of disease in companion animals is increasing rapidly. The gene defects may be differentiated in an initiating defect, which is the cause of illness, and a promoting defect, which enhances the chance on illness. Up till now only initiating defects are known in dogs and cats. All this is of great importance for breeding purposes, because within a breed there is narrow relationship which means the genetic diversity is small, and with all the disadvantages thereof. The identification in good time of gene defects in breeding animals, so that these animals being excluded from breeding, is of utmost importance in preventing congenital diseases. For that reason more and more the owners will appeal to veterinary surgeons to cooperate in procedures to screen potential breeding animals, or to declare the animals free from gene defects. The problems with regard to the diagnostic tests, including the DNA-tests, and their predictive values are discussed.

Animals↗

PubMed2005

A direct interview family study of obsessive-compulsive disorder. I.

BACKGROUND: This and the companion paper present two sequential family studies of obsessive-compulsive disorder (OCD) conducted by the same research group, but with different sampling and best-estimate procedures. In addition to providing further data on familial transmission of OCD, we used comparison of disparate findings (moderate, specific familial aggregation in this first study versus a stronger effect for other anxiety disorders than for OCD alone in the second) to examine possible effects of proband characteristics and informant data on outcome. METHOD: In this initial study we interviewed 179 first-degree relatives of 72 OCD probands and 112 relatives of 32 never mentally ill (NMI) controls. Informant data were obtained on an additional 126 relatives (total "combined" samples of 263 and 154 respectively). Analyses used best-estimate diagnoses made by consensus of two "blinded" senior clinicians who reviewed all diagnostic materials including proband informant data about relatives. RESULTS: Significantly higher risk for OCD but not other anxiety disorders was found in relatives of OCD probands compared to relatives of controls in both the directly interviewed and combined samples. There was no relationship between proband age at onset of OCD and strength of familial aggregation. CONCLUSIONS: These data indicate moderate familial aggregation of OCD, but do not support increased transmission by early onset probands, or a familial relationship between OCD and other anxiety disorders with the possible exception of generalized anxiety disorder.

Adult↗

PubMed2004

Genomewide linkage scan for bipolar-disorder susceptibility loci among Ashkenazi Jewish families.

The relatively short history of linkage studies in bipolar disorders (BPs) has produced inconsistent findings. Implicated regions have been large, with reduced levels of significance and modest effect sizes. Both phenotypic and genetic heterogeneity may have contributed to the failure to define risk loci. BP is part of a spectrum of apparently familial affective disorders, which have been organized by severity. Heterogeneity may arise because of insufficient data to define the spectrum boundaries, and, in general, the less-severe disorders are more difficult to diagnose reliably. To address the inherent complexities in detecting BP susceptibility loci, we have used restricted diagnostic classifications and a genetically more homogeneous (Ashkenazi Jewish) family collection to perform a 9-cM autosomal genomewide linkage scan. Although they are genetically more homogeneous, there are no data to suggest that the rate of illness in the Ashkenazim differs from that in other populations. In a genome scan of 41 Ashkenazi pedigrees with a proband affected with bipolar I disorder (BPI) and at least one other member affected with BPI or bipolar II disorder (BPII), we identified four regions suggestive of linkage on chromosomes 1, 3, 11, and 18. Follow-up genotyping showed that the regions on chromosomes 1, 3, and 18 are also suggestive of linkage in a subset of pedigrees limited to relative pairs affected with BPI. Furthermore, our chromosome 18q22 signal (D18S541 and D18S477) overlaps with previous BP findings. This research is being conducted in parallel with our companion study of schizophrenia, in which, by use of an identical approach, we recently reported significant evidence for a schizophrenia susceptibility locus in the Ashkenazim on chromosome 10q22.

Bipolar Disorder↗

PubMed2000

Pet insurance--essential option?

As Hawn (2) says, "insurance is about risk and peace of mind." She reports that the American Humane Society supports pet insurance because companion animals are able to be treated for disease or accidents that are life-threatening where, otherwise, they would have been euthanized. For veterinarians, she suggests that pet insurance allows them to practice veterinary medicine "as if it were free." It is inevitable that pet insurance will grow as a recourse for veterinary fees. This may be a savior to some families whose budget is stretched to the limit at a critical moment in the health care of their cherished pet. We in the veterinary profession have an advantage over other professions. We have seen the good, the bad, and the ugly of insurance, as it applies to human health and dental care. If we work hand-in-hand with our own industries, collectively we may be able to develop a system that wins for everyone, with fees that allow practice to thrive and growth strategies that accommodate new treatment and diagnostic modalities, as well as consistent and exemplary customer service. The path ahead is always fraught with bumps and potholes. We can be a passive passenger and become a victim of the times or an active driver to steer the profession to a clearer route. Pet insurance is but one of the solutions for the profession; the others are a careful assessment of our fees--charging what we are worth, not what we think the client will pay; business management; customer service; leadership of our health care team; lifelong learning; and more efficient delivery systems. Let us stop being a victim, stop shooting ourselves in the professional foot, and seize the day!

Animal Diseases↗

PubMed2005

Human behaviour and the epidemiology of parasitic zoonoses.

The behaviour of Homo sapiens has a pivotal role to play in the macro and microepidemiology of emerging or re-emerging parasitic zoonoses. Changing demographics and the concomitant alterations to the environment, climate, technology, land use and changes in human behavior, converge to favour the emergence and spread of parasitic zoonoses. The recent unprecedented movements of people, their animals and their parasites around the world, introduce and mix genes, cultural preferences, customs, and behavioral patterns. The increasing proclivity for eating meat, fish, crabs, shrimp, molluscs raw, undercooked, smoked, pickled or dried facilitates a number of protozoan (Toxoplasma), trematode (Fasciola sp., Paragonimus spp., Clonorchis sp., Opisthorchis spp., Heterophyes sp., Metagonimus sp., Echinostoma spp., Nanophyetus sp.) cestode (Taenia spp, Diphyllobothrum sp.) and nematode (Trichinella spp., Capillaria spp., Gnathostoma spp., Anisakis sp., Parastrongylus spp.) caused zoonoses. The increasing world population and the inability to keep pace with the provision of adequate sanitation and clean, safe drinking water, has led to an increased importance of waterborne zoonoses, such as those caused by Giardia, Cryptosporidium and Toxoplasma. Our close relationship with and the numerous uses to which we put companion animals and their ubiquitous distribution has resulted in dogs and cats unwitting participation in sharing over 60 parasite species including: Giardia, Cryptosporidium, Toxoplasma, most foodborne trematode species, Diphyllobothrum, Echinococcus spp., Ancylostoma and Toxocara. Changing human behaviour through education, to encourage the proper cooking of food, which may have cultural and social significance, will remain as challenging as controlling stray and feral pet populations, improving hygiene levels and the provision of safe drinking water and the proper use of sanctuary facilities. Long pre-patent periods and the normally insidious sub-clinical nature of most zoonoses makes advice requiring behavioural change for their control a difficult task. Our clearer understanding of the heterogeneity of susceptibility to infection, the complex genetic variations of people and parasite species and the development of molecular epidemiological tools is shedding more light on transmission routes and the spectrum of disease that is observed. Improved and new serological, molecular and imaging diagnostic tests and the development of broad spectrum chemotherapeutic agents has led to the attenuation of morbidity and mortality due to parasitic zoonoses in economically advantaged regions. Such advancements, in partnership with supportive behavioural change, has the potential for a sustainable global reduction in the burden of ill health due to parasitic zoonoses. Whether this will materialise is a challenge for us all.

Animals↗

PubMed1988

Guidelines for clinical protocols for chronic lymphocytic leukemia: recommendations of the National Cancer Institute-sponsored working group.

The National Cancer Institute (NCI)-sponsored Chronic Lymphocytic Leukemia (CLL) Working Group was convened to develop a set of standardized eligibility, response, and toxicity criteria for clinical trials. We recognized the previous efforts in 1967 (published again in 1973 as the report of the Chronic Leukemia-Myeloma Task Force [1] and 1978 of Cancer and Leukemia Group B (CALGB) [2]). We have used these reports for guidance during the current effort. Several noteworthy developments in the past few years have made it necessary to modify the previous guidelines. First, the diagnostic criteria for CLL and its clinical staging have been developed and well defined. Second, although staging systems facilitated entry of comparable and relatively homogeneous groups of patients in clinical trials, the definitions of response (CR) and partial response (PR) were not uniformly adopted from the previous guidelines in the clinical trials (Tables IA, IB); therefore, comparisons of results obtained in different studies became difficult. Third, there has been an improvement in our understanding of the immunology and biology of CLL. Finally, we are witnessing the emergence of several chemotherapy agents that promise impressive activity in CLL (e.g., 2'-deoxycoformycin [3], fludarabine monophosphate [4, 5]), and thereby offer the potential for improving survival time in this disease. To best identify regimens worthy of continued pursuit in large comparative trials, standardized guidelines for evaluation are essential. A number of laboratory investigations are also presented for which scientific interest is high yet relevance remains to be determined; thus, they are presented as companion studies to the clinical trials. This mechanism allows for flexibility in the testing of these questions and for additional ideas in the future without requiring modification of an entire treatment protocol. The following guidelines were developed to be used as a form of standardization for clinical trials, incorporating current technologies, yet remaining relevant to the general hematology/oncology community. Based on the membership of the Working Group, it is expected that these guidelines will serve as the criteria for most clinical trials in the near future.

Antineoplastic Agents↗

PubMed1980

Immunochemical detection of fecal occult blood--the fecal smear punch-disc test: a new non-invasive screening test for colorectal cancer.

An immunochemical test for fecal occult blood was developed for use in colon cancer screening. The test employs high titer monospecific antisera to intact human hemoglobin in a radial immunodiffusion assay. Patient smears on specially treated filter paper allow screening procedures similar to those using Hemoccult slides. Minimum detectible hemoglobin was 0.3 mg/gm stool, and no cross reactivity with dietary constituents, drugs, or chemicals occurred. The accession of 150 consecutive cases of colon-rectal carcinoma was accomplished from three community hospitals. In each instance, at least one preoperative fecal specimen was obtained for companion smear testing with immunochemical punch-disc and commercial Hemoccult slides. Twenty-nine percent of the cases were found not to be bleeding by either test. Occult bleeding was detected by Hemoccult in 40% of the cases, and occult bleeding was detected by immunochemical testing in 65% of the cases. A surprising discovery was that rectal lesions had a much lower rate of of positiuity with both tests (Hemoccult-29%, Immunochemical-50%) than other locations. These results suggest that immunochemical screening for occult blood loss will provide a higher rate of detection of colon cancer.

Adenocarcinoma↗

PubMed1991

Straddling mitral valve with hypoplastic right ventricle, crisscross atrioventricular relations, double outlet right ventricle and dextrocardia: morphologic, diagnostic and surgical considerations.

The clinical, surgical and morphologic findings in five cases of a rare form of straddling mitral valve are presented. Three patients were diagnosed by two-dimensional echocardiography, cardiac catheterization and angiocardiography and two had diagnostic confirmation at autopsy. All five cases shared a distinctive and consistent combination of anomalies: 1) dextrocardia; 2) visceroatrial situs solitus, concordant ventricular D-loop and double outlet right ventricle with the aorta positioned to the left of and anterior to the pulmonary artery; 3) hypoplasia of right ventricular inflow (sinus) with tricuspid valve stenosis or hypoplasia; 4) large right ventricular infundibulum (outflow); 5) malalignment conoventricular septal defect; 6) straddling mitral valve with chordal attachments to the left ventricle and right ventricular infundibulum; 7) severe subpulmonary stenosis with well developed pulmonary arteries; and 8) superoinferior ventricles with crisscross atrioventricular (AV) relations. The degree of malalignment between the atrial and ventricular septa was studied quantitatively by measuring the AV septal angle projected on the frontal plane. The AV septal angle in the two postmortem cases was 150 degrees, reflecting marked malalignment of the ventricles relative to the atria. This AV malalignment appears to play an important role in the morphogenesis of straddling mitral valve. As judged by a companion study of seven postmortem cases, the more common form of straddling mitral valve with a hypertrophied and enlarged right ventricular sinus had less severe ventricular malposition than did the five rare study cases with hypoplastic right ventricular sinus. A competent mitral valve, low pulmonary vascular resistance and low left ventricular end-diastolic pressure were found at cardiac catheterization in the three living patients who underwent a modified Fontan procedure and are doing well 2.2 to 5.8 years postoperatively.

Adult↗

PubMed2004

Food animal veterinary medicine: leading a changing profession.

The veterinary profession has gone through periods of profound change in response to economic and social changes. We are currently in another such period: profound change is required in order for the profession to remain relevant in a marketplace where a rapidly expanding knowledge base and new technologies demand an ever-increasing level of expertise in a greater variety of areas. However, the veterinary profession is perceived both internally and by the public as possessing a narrow set of skills that supports a narrow group of careers focused on salvaging ill or injured companion animals. It will be necessary to dramatically change the way veterinary students are recruited and trained, as well as how graduate veterinarians are licensed and provided continuing education, in order for the veterinary profession to capitalize on our historical strengths and provide service and leadership in a greater diversity of career paths. Even though the number of veterinarians needed to provide primary care for livestock is decreasing, both the level of expertise demanded by livestock owners and the value of veterinary involvement on livestock farms are increasing. Colleges of veterinary medicine appear challenged to meet the changing needs for veterinary services in animal agriculture because of the declining percentage of veterinary students interested in food animal careers. Fortunately for animal agriculture, the skill set needed by food animal veterinarians is also needed by several emerging segments of the veterinary profession that have tremendous potential for rapid growth, including employment in all segments of food production systems, environmental monitoring and management, bio-security and disease eradication, laboratory diagnostics, and federal regulatory and bio-defense roles. Like previous periods of profound change, this moment in history will require creative thought, open discussion, and a willingness to step into the unknown.

Animals↗

PubMed2006

Neuroethical responsibilities.

Neuroscience represents a dynamic area of biomedical research where neuroethical responsibilities for researchers are emerging. This paper is the companion piece to the French-language one also published in this issue of the Canadian Journal of Neurological Sciences. It serves as a review of recent advances in neuroethics through the lens of three cases: (1) incidental finding of anomalies in neuroimaging research; (2) creation of neurotechnologies that can lead to cognitive enhancement, and (3) responsible communication of research results. We propose and discuss a multidimensional framework of neuroethical responsibilities to help tackle these issues. The framework reiterates the fundamental role of scientific integrity, puts in the foreground social responsibilities pertaining to the eventual use of neuroscience knowledge, and highlights self-reflection in research and training of researchers.

Cognition↗

PubMed2002

Improvement of serological discrimination between herpesvirus-infected animals and animals vaccinated with marker vaccines.

Control/eradication plans of bovine herpesvirus 1 (BHV1) and suid herpesvirus 1 (SHV1) infections involve vaccination with inactivated or attenuated gE-deleted marker vaccines and associated companion serological tests to discriminate naturally infected from vaccinated animals. Blocking or competitive enzyme-linked immunosorbent assays (ELISAs) have been designed for the detection of specific antibodies against BHV1 or SHV1 gE glycoprotein. The antigen source usually consists of a crude viral preparation in which gE is associated with other envelope glycoproteins. Such assays suffer from a lack of specificity which is not due to serological cross-reactions with other pathogens. Interestingly, false-positive results occur with sera collected from multivaccinated cattle or pigs. After multivaccination with a marker vaccine, the binding of the conjugated monoclonal antibody used as a tracer, could be hampered by antibodies directed against the other viral glycoproteins. In order to validate the steric hindrance hypothesis, a simple preadsorption of such samples was carried out with a preparation of antigen devoid of gE, prior to the blocking ELISA itself. The decrease in antibody concentrations against the major glycoproteins, clearly leads to a better discrimination between positive and negative samples; that is between infected and multivaccinated animals, without significant loss of sensitivity. This experiment confirms the steric hindrance hypothesis, therefore serum preadsorption could be an easy way to improve the specificity of currently available diagnostic tests.

Animals↗