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PubMed2006

Authorship versus "credit" for participation in research: a case study of potential ethical dilemmas created by technical tools used by researchers and claims for authorship by their creators.

The distinction between authorship and other forms of credit for contribution to a publication has been a persisting controversy that has resulted in numerous guidelines outlining the expected contributions of those claiming authorship. While there have been flagrant, well-publicized deviations from widely accepted standards, they are largely outnumbered by cases that are not publicity-worthy, and therefore remain known to only those directly involved with the inappropriate conduct. We discuss the definition and ethical requirements of authorship, offer a case example of the authorship debate created by a technical tool at our institution, and review parallels that support and dispute the authorship claims of our software developers. Ultimately, we conclude that development of a technical tool that enables data collection does not adequately substitute for contributions to study design and manuscript preparation for authorship purposes. Unless the designers of such a technical tool prospectively participate as a part of the project, they would not have an adequate understanding of the publication's genesis to defend it publicly and cannot be listed as authors. Therefore, it is incumbent upon project members to invite tool developers to participate at the beginning of such projects, and for tool developers to contribute to study design and manuscript preparation when they desire authorship listings.

Authorship↗
PubMed2006

Spectral mapping tools from the earth sciences applied to spectral microscopy data.

BACKGROUND: Spectral imaging, originating from the field of earth remote sensing, is a powerful tool that is being increasingly used in a wide variety of applications for material identification. Several workers have used techniques like linear spectral unmixing (LSU) to discriminate materials in images derived from spectral microscopy. However, many spectral analysis algorithms rely on assumptions that are often violated in microscopy applications. This study explores algorithms originally developed as improvements on early earth imaging techniques that can be easily translated for use with spectral microscopy. METHODS: To best demonstrate the application of earth remote sensing spectral analysis tools to spectral microscopy data, earth imaging software was used to analyze data acquired with a Leica confocal microscope with mechanical spectral scanning. For this study, spectral training signatures (often referred to as endmembers) were selected with the ENVI (ITT Visual Information Solutions, Boulder, CO) "spectral hourglass" processing flow, a series of tools that use the spectrally over-determined nature of hyperspectral data to find the most spectrally pure (or spectrally unique) pixels within the data set. This set of endmember signatures was then used in the full range of mapping algorithms available in ENVI to determine locations, and in some cases subpixel abundances of endmembers. RESULTS: Mapping and abundance images showed a broad agreement between the spectral analysis algorithms, supported through visual assessment of output classification images and through statistical analysis of the distribution of pixels within each endmember class. CONCLUSIONS: The powerful spectral analysis algorithms available in COTS software, the result of decades of research in earth imaging, are easily translated to new sources of spectral data. Although the scale between earth imagery and spectral microscopy is radically different, the problem is the same: mapping material locations and abundances based on unique spectral signatures.

Algorithms↗
PubMed1993

Curriculum Analysis Tools (CATs): a cooperative approach to the design of curriculum databases.

In 1990, a small group of dental schools agreed to pool their resources and cooperate in the design and programming of curriculum analysis software. After two and one half years, the consortium which was formed has grown to include over 50 institutions. Its efforts have been endorsed by the American Association of Dental Schools and it is now beta testing its first software product, known as CATs, which is an acronym for Curriculum Analysis Tools. The process by which the software has been developed, as well as its current design, offers a unique blend of flexibility and creativity which could perhaps be adopted by other health professions.

Curriculum↗
PubMed2000

NMR spectroscopy in drug discovery: tools for combinatorial chemistry, natural products, and metabolism research.

NMR spectroscopy has enjoyed many advances recently, and the pace of development shows no signs of slowing. This article focuses on advances that have affected solution-state NMR. These advances fall into three general categories: new experimental techniques (new pulse sequence tools), improved hardware and more powerful software. These advances are allowing NMR to help solve important problems in the field of drug discovery. Their impact is widespread. NMR spectroscopy is now being used to determine protein structures, to monitor ligand-receptor binding, to study diffusion, to analyze mixtures using LC-NMR, to analyze solid-phase synthesis resins and to determine the structures of organic small molecules. NMR spectroscopy can provide both qualitative and quantitative information, and can be used in both routine analytical applications and demanding research applications. The applications described here can benefit numerous disciplines in drug discovery, including natural products research, synthetic medicinal chemistry, metabolism studies, drug production, quality control, rational drug design and combinatorial chemistry.

Animals↗
PubMed1988

New developments in medical microbiology: computer-assisted diagnosis and automated instruments.

Time and accuracy required for diagnosis are two of the most important factors in medical microbiology. Computer-assisted diagnosis is one tool to overcome these problems. The software of such systems, much more than the hardware, is of utmost importance and both have to fulfill several items. 1) High flexibility and integration within the already existing working schemes of the laboratory. 2) Terminals in every laboratory. 3) High speed of calculation. 4) Online data transfer from automated instruments. 5) External terminals on intensive care units. 6) Epidemiological and etiopathological investigations have to be possible at any time. In the laboratory the burden of simple, repeating tasks is diminished, inquiries can be made in a minute and precise information about the epidemiological situation can be gained within a few hours. Thus, calculated antimicrobial therapy depending on the incidence of certain pathogens in given specimens in different departments is possible. In the case of fast-growing bacteria, preliminary reports, including susceptibility testing available within the first 24 h, are possible and will be of great help to the clinician in monitoring the calculated antimicrobial regimen. External terminals will allow continuous flow of data from the laboratory to wards and vice versa.

Autoanalysis↗
PubMed2006

PIXImus bone densitometer and associated technical measurement issues of skeletal growth in the young rat.

The PIXImus dual-energy X-ray absorptiometer (DXA) is designed to measure body composition, bone mineral content (BMC), area (BA), and density (BMD) in mice and rats. The aims of this study were to longitudinally measure BMC, BA, and BMD in growing rats and to identify potential technical problems associated with the PIXImus. Total femur and lumbar DXA measurements, body weight, and length of initially 3-week-old rats (n = 10) were taken at weeks 5, 9, and 14. BMC and BMD of femoral metaphyseal and diaphyseal regions rich in trabecular and cortical bone, respectively, were obtained. Results showed significant increases in body weight, total femur BMC and BMD, lumbar area, length, BMC, and BMD at each time point. There was a significant positive correlation between body weight and total femur BMD (r = 0.97, P < 0.001) as well as lumbar BMD (r = 0.99, P < 0.001). BMD values for the femoral metaphyseal region and the lumbar spine were also positively correlated (r = 0.96, P < 0.01). Several technical issues (e.g., positioning of animals), difficulties (e.g., in analysis of images), and limitations (e.g., inability to detect underdeveloped calcified bone in growing animals and bone edge detection) of the software pertinent to the PIXImus were evident. In conclusion, despite limitations in the software, the PIXImus is a valuable tool for studying skeletal development of growing rats.

Absorptiometry, Photon↗
PubMed2006

Automated quality control in computed radiography.

PURPOSE: The purpose of this paper is to describe the automation of quality control procedures on photo-stimulable imaging plates by means of an image-processing tool providing automatic reading of the images and automatic calculation of the quality parameters monitored. MATERIALS AND METHODS: Quality-control procedures were performed according to the main available guidelines. The quality assurance programme was applied to several Kodak and Philips devices in four radiological departments. The automatic image-processing tool was developed using public domain software (Java-based ImageJ software) and contains both reading and computation procedures. RESULTS: The quality checks and algorithms described were successfully applied, proving useful for identification of defective plates and for implementation of the quality assurance programme. The use of automation allowed significant savings in the time required for quality checks. CONCLUSIONS: Completely automated image reading allows substantial economic and human resources savings, as it eliminates much of the transfer, reproduction, processing and filing procedures.

Algorithms↗
PubMed2006

Tattooing of the nipple-areola complex: review of outcome in 40 patients.

Reconstruction of a pigmented nipple-areola complex (NAC) is one of the final steps in rehabilitating patients following mastectomy. We report the results of 40 consecutive patients who had NAC tattooing done by the same surgeon. Assessments were made both subjectively using a questionnaire, and objectively by using a computer software programme (Adobe Photoshop) to analyse the colour of the NACs. Follow up ranged between six and 24 months (mean 14 months). One patient suffered an infection, and was the only one to need repeat tattooing in our series. Thirty-seven patients (92%) reported some colour fading which ranged between 5% and 80% (mean 32%). A grade of good or very good was given by 33 patients (82%) for colour match, by 36 patients (90%) for over all satisfaction, and by 34 patients (85%) for enhancement in body image. An analysis of the colours of the tattooed and unoperated NACs by the software programme showed that they were similar to a value that ranged from 78% to 97% (mean 91%). Tattooing is a simple and safe procedure, and despite some colour asymmetry it still has a high satisfaction rate. It significantly improves patient's perception of body image. An objective assessment of tattooing using a computer software programme can be a useful tool in reviewing the outcome. Video clips (1-5) are included with the paper for demonstration of the tattooing technique (re-arranged from the video presented with the paper at BAPS).

Adult↗
PubMed2004

Perl-speaks-NONMEM (PsN)--a Perl module for NONMEM related programming.

The NONMEM program is the most widely used nonlinear regression software in population pharmacokinetic/pharmacodynamic (PK/PD) analyses. In this article we describe a programming library, Perl-speaks-NONMEM (PsN), intended for programmers that aim at using the computational capability of NONMEM in external applications. The library is object oriented and written in the programming language Perl. The classes of the library are built around NONMEM's data, model and output files. The specification of the NONMEM model is easily set or changed through the model and data file classes while the output from a model fit is accessed through the output file class. The classes have methods that help the programmer perform common repetitive tasks, e.g. summarising the output from a NONMEM run, setting the initial estimates of a model based on a previous run or truncating values over a certain threshold in the data file. PsN creates a basis for the development of high-level software using NONMEM as the regression tool.

Computer Simulation↗
PubMed2005

A Java application for tissue section image analysis.

The medical industry has taken advantage of Java and Java technologies over the past few years, in large part due to the language's platform-independence and object-oriented structure. As such, Java provides powerful and effective tools for developing tissue section analysis software. The background and execution of this development are discussed in this publication. Object-oriented structure allows for the creation of "Slide", "Unit", and "Cell" objects to simulate the corresponding real-world objects. Different functions may then be created to perform various tasks on these objects, thus facilitating the development of the software package as a whole. At the current time, substantial parts of the initially planned functionality have been implemented. Getafics 1.0 is fully operational and currently supports a variety of research projects; however, there are certain features of the software that currently introduce unnecessary complexity and inefficiency. In the future, we hope to include features that obviate these problems.

Cytological Techniques↗
PubMed2006

Supporting disaster healthcare professionals: a practical and virtual approach.

In this paper, we report on a questionnaire undertaken to evaluate an innovative programme of education for healthcare professionals in the field of aid and disaster healthcare that has been delivered by a partnership of three Higher Education Institutions (HEIs) across Europe since 1999. The development of this programme was a direct response to the stated needs of Non Government Organisations (NGOs) and military healthcare professionals as well as those aspiring to enter this complex area of healthcare. The aim of the project was to evaluate whether the programme was meeting the needs of students and to elicit what improvements could be made to the programme in order to enhance the learning experience. A questionnaire was developed to gather data across seven areas. It was subsequently analysed using the report and statistics features available within WebCT's Quiz/Questionnaire tool, in addition to the spreadsheet software MS Excel. The results of the questionnaire confirm that the programme, while successful in many ways, needs to be modified on a regular basis to reflect relevant worldwide changes and would benefit greatly from increased interaction between faculty and students.

Adult↗
PubMed1998

Evaluation of visual and instrument shade matching.

STATEMENT OF PROBLEM: Visual color matching to determine shades in dentistry is inconsistent and unreliable. If accurate, instrumental measurement of tooth color would provide objective, quantified data to match natural teeth to clinical shade guides. PURPOSE: This study evaluated and compared the ability of a new computerized colorimeter and a simple visual test to match ceramic shade guide teeth. MATERIAL AND METHODS: Thirty-one (n = 31) observers with normal color vision were allowed unlimited time to match one set of Vita Lumin shade guide teeth to the corresponding shade guide teeth of a second Vita Lumin shade guide. The same test was administered to 14 of the observers several months later to determine within-subject variability. A computerized colorimeter (Colortron II) equipped with a positioning guide was used to measure the middle third of each shade guide tooth. Through a "match tool" present in the computer's software, readings from one shade guide were matched with readings of the other shade guide by using CIELAB measurements and DeltaE values. The mean number of correct matches by the colorimeter and of correct matches in visual test were compared with a 1-tailed t test. Repeatability for both tests was determined with a paired t test. RESULTS: The Colortron II instrument correctly matched 8 of the 16 tabs (50% correct), whereas visual matching by examiners averaged 7. 7 of 16 correct matches (48% correct) (standard deviation 2.7). No statistically significant differences existed between the 2 methods. The colorimeter demonstrated 100% repeatability and the visual test demonstrated fair repeatability (correlation coefficient r =.60). CONCLUSIONS: Shade determination by visual means was inconsistent. Accuracy of a new colorimeter in matching porcelain shade guide teeth was only slightly better.

Ceramics↗
PubMed2001

The outcome of retinopathy of prematurity: screening for retinopathy of prematurity using an outcome predictive program.

PURPOSE: The purpose of this study was to compare the calculated risk of progression to threshold retinopathy of prematurity (ROP) and risk of an unfavorable structural outcome using the computer program, RM-ROP, with the observed incidence for infants born at Jackson Memorial Hospital (JMH) and to determine how many children would have been treated unnecessarily if the threshold criteria for treatment were lowered on the basis of the clinical findings and RM-ROP risk calculations. DESIGN: Noncomparative interventional case series. PARTICIPANTS: All 292 surviving premature infants weighing 1250 g or less at birth and born at JMH between January 1, 1997, and December 31, 1998, were included in the study. METHODS: Baseline demographic factors and data from sequential ophthalmic examinations were entered into the RM-ROP program for risk calculation. Infants reaching threshold disease received diode laser indirect photocoagulation of the avascular retina. Three-month follow-up was obtained for infants receiving laser treatment. MAIN OUTCOME MEASURES: The development of threshold ROP and an unfavorable structural outcome, defined as a posterior retinal fold or posterior retinal detachment occurring within 3 months of threshold disease. RESULTS: Thirty-eight eyes were diagnosed with threshold ROP, with 18 of 20 subjects having bilateral disease. Three-month posttreatment follow-up was obtained on all 20 children, with 19 having good structural outcomes. Thirty-two percent of eyes (12 of 38) reaching threshold never had a risk estimate greater than 0.10. However, only 6% of eyes (35 of 546) that did not reach threshold ever had a model predicted risk greater than 0.15. All right eyes with zone 1 prethreshold disease, 60% of those with zone 2 stage 2+ disease, and 23% with zone 2 stage 3 disease progressed to threshold ROP. CONCLUSIONS: The similarity between the risk distributions for the Miami and the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity study indicates the similarity in the populations with respect to risk factors identified as important by the model. The Miami data validated the model, with eyes reaching threshold having higher risks than eyes that did not. Actual risk estimates for eyes reaching threshold can be small. Changing the threshold criteria for treatment on the basis of various clinical and computer-generated prethreshold risk levels in our population would have resulted in the unnecessary treatment of many infants who never progressed to threshold disease. In the Miami population, if the model were used to manage an individual subject, close attention would have to be paid to small differences in risk. Although the RM-ROP software program may be a useful tool for following premature infants with ROP, the clinical examination remains the "gold standard."

Disease Progression↗
PubMed2005

Evolution of matrix and bone gamma-carboxyglutamic acid proteins in vertebrates.

The evolution of calcified tissues is a defining feature in vertebrate evolution. Investigating the evolution of proteins involved in tissue calcification should help elucidate how calcified tissues have evolved. The purpose of this study was to collect and compare sequences of matrix and bone gamma-carboxyglutamic acid proteins (MGP and BGP, respectively) to identify common features and determine the evolutionary relationship between MGP and BGP. Thirteen cDNAs and genes were cloned using standard methods or reconstructed through the use of comparative genomics and data mining. These sequences were compared with available annotated sequences (a total of 48 complete or nearly complete sequences, 28 BGPs and 20 MGPs) have been identified across 32 different species (representing most classes of vertebrates), and evolutionarily conserved features in both MGP and BGP were analyzed using bioinformatic tools and the Tree-Puzzle software. We propose that: 1) MGP and BGP genes originated from two genome duplications that occurred around 500 and 400 million years ago before jawless and jawed fish evolved, respectively; 2) MGP appeared first concomitantly with the emergence of cartilaginous structures, and BGP appeared thereafter along with bony structures; and 3) BGP derives from MGP. We also propose a highly specific pattern definition for the Gla domain of BGP and MGP.

Amino Acid Sequence↗
PubMed2005

enoLOGOS: a versatile web tool for energy normalized sequence logos.

enoLOGOS is a web-based tool that generates sequence logos from various input sources. Sequence logos have become a popular way to graphically represent DNA and amino acid sequence patterns from a set of aligned sequences. Each position of the alignment is represented by a column of stacked symbols with its total height reflecting the information content in this position. Currently, the available web servers are able to create logo images from a set of aligned sequences, but none of them generates weighted sequence logos directly from energy measurements or other sources. With the advent of high-throughput technologies for estimating the contact energy of different DNA sequences, tools that can create logos directly from binding affinity data are useful to researchers. enoLOGOS generates sequence logos from a variety of input data, including energy measurements, probability matrices, alignment matrices, count matrices and aligned sequences. Furthermore, enoLOGOS can represent the mutual information of different positions of the consensus sequence, a unique feature of this tool. Another web interface for our software, C2H2-enoLOGOS, generates logos for the DNA-binding preferences of the C2H2 zinc-finger transcription factor family members. enoLOGOS and C2H2-enoLOGOS are accessible over the web at http://biodev.hgen.pitt.edu/enologos/.

Amino Acids↗
PubMed1997

An investigation of the relationship between ultrasound echo enhancement and Doppler frequency shift using a pulsatile arterial flow phantom.

RATIONALE AND OBJECTIVES: Based on the echo-enhancing effect of microbubbles, various agents have been developed to improve the diagnostic confidence in patients with inadequate Doppler signals. In the clinical trials of the echo enhancer Levovist, there were a few isolated cases in which the maximum flow velocities of the enhanced Doppler spectra appeared to higher than the velocities in the nonenhanced baseline spectra. This raised the concern that echo enhancement could give a false indication of maximum flow velocity. This study investigated whether a systematic association between echo enhancement and velocity shift exists. METHODS: A pulsatile flow phantom that simulated the elasticity of blood vessels and the acoustic attenuation of extravascular tissue was used to compare enhanced with unenhanced Doppler spectra under accurately reproducible flow conditions. The experiments were carried out with varied sound attenuation and evaluated with dedicated spectral analysis software that included a special averaging tool. RESULTS: Levovist enhanced the Doppler signal by 16 to 31 dB, and the enhanced and unenhanced power spectra presented identical distribution of spectral power density under all flow conditions. CONCLUSIONS: The measurements gave no evidence that echo enhancement with Levovist falsifies the Doppler measurement of flow velocity.

Blood Flow Velocity↗
PubMed2004

Advances in statistical methodology and their application in critical care.

PURPOSE OF REVIEW: To review some of the major advances in statistical methodology of the past two decades and their application to investigations in critical care. RECENT FINDINGS: The introduction of new technologies and the ready availability of advanced computer resources have led to significant developments in statistical methodology. These include the development of computationally intensive methods, improved methods for modeling correlated outcome data, and new methods for handling missing data. Although many of these tools are available in standard statistical software, they remain underutilized in the medical literature. SUMMARY: By becoming familiar with advances in statistical methodology, researchers and clinicians can enhance collaboration with their statistical colleagues, toward the goal of better study design and analysis.

Critical Care↗
PubMed2025

Beyond Blacklists: A Critical Assessment of Exclusion Set Generation Strategies and Alternative Approaches.

Short-read sequencing data can be affected by alignment artifacts in certain genomic regions. Removing reads overlapping these exclusion regions, previously known as Blacklists, help to potentially improve biological signal. Tools like the widely used Blacklist software facilitate this process, but their algorithmic details and parameter choices are not always clearly documented, affecting reproducibility and biological relevance. We examined the Blacklist software and found that pre-generated exclusion sets were difficult to reproduce due to variability in input data, aligner choice, and read length. We also identified and addressed a coding issue that led to over-annotation of high-signal regions. We further explored the use of "sponge" sequences-unassembled genomic regions such as satellite DNA, ribosomal DNA, and mitochondrial DNA-as an alternative approach. Aligning reads to a genome that includes sponge sequences reduced signal correlation in ChIP-seq data comparably to Blacklist-derived exclusion sets while preserving biological signal. Sponge-based alignment also had minimal impact on RNA-seq gene counts, suggesting broader applicability beyond chromatin profiling. These results highlight the limitations of fixed exclusion sets and suggest that sponge sequences offer a flexible, alignment-guided strategy for reducing artifacts and improving functional genomics analyses.

Journal Article↗