bluuebunny/crossref_metadata_2025 huggingface dataset:
Polysulphated glycosaminoglycans modulate transcription of interleukin-1β treated chondrocytes in monolayer culture
Authors: MacLeod J. N. , Fubini S. L. , Vernier-Singer M. , Nixon A. J. , Todhunter R. J. , Mertens W. D.
Published: March 2018

The ability of polysulphated glycosaminoglycans (PSGAGs, Adequan®) to modulate the transcription of major articular cartilage matrix proteins and enzymes was examined. Northern blot analyses were used to compare steady-state mRNA levels of type-II procollagen, aggrecan core protein, matrix metalloproteinase (MMP)-1, MMP-3, tissue inhibitor of metalloproteinase (TIMP)-1, and TIMP-3 in equine chondrocytes grown in monolayer culture. The groups included: control, low-dose (0.1mg/ml) Adequan®, high-dose (1.0mg/ml) Adequan®, IL-1 β (10ng/ml), IL-1 β with low-dose Adequan®, and IL-1 β with high-dose Adequan®. The responses (p<0.05) to treatment were compared with one-way analysis of variance and post hoc least significant difference test. Interleukin-1 β significantly decreased steady-state levels of type-II procollagen (0.5x) and aggrecan core protein (to undetectable levels) and significantly increased MMP-1 (11.7x), MMP-3 (1.8x), TIMP-1 (1.9x), and TIMP-3 (5.1 x). Adequan® alone significantly increased steady-state mRNA levels of type-II procollagen (1.6x) and decreased MMP-1 (0.3x at high-dose only), MMP-3 (0.5x), and TIMP-1 (0.3x at high-dose only). In IL-1 β-treated chondrocytes, Adequan® significantly increased steady-state mRNA levels of type-II procollagen (1.4x of IL-1 β-treated levels), aggrecan core protein (IL-1 β -treated had no detectable expression), and MMP-3 (3.6 x at high dose) and significantly decreased steady-state mRNA levels of MMP-1 (0.3 x), and TIMP-1 (0.2x). This study is the first to demonstrate that Adequan® alters steady-state mRNA levels of key matrix proteins and enzymes; that it counteracts some of the deleterious effects of IL-1 β; and that these effects are in part dose-dependent.
Arthrotomy versus arthroscopy in the treatment of the fragmented medial coronoid process of the ulna (FCP) in 421 dogs
Authors: Langhann A. , Fehr M. , Nolte I. , Meyer-Lindenberg A.
Published: March 2018

In a retrospective trial over eight years 518 joints from 421 dogs with fragmented medial coronoid process of the ulna (FCP) were included. Seventy-five joints had an additional osteochondrosis dissecans of the medial aspect of the humeral condyle. Forty-six point eight percent of the dogs (197/421) were younger than one year. Two hundred and forty-seven joints were treated by conventional arthrotomy and 271 joints were treated by arthroscopy. Two hundred and thirty-eight cases (103 treated by arthrotomy and 135 by arthroscopy) were re-evaluated clinically and radiographically and 191 cases (88 treated by arthrotomy and 103 by arthroscopy) by means of a questionnaire at an average of 23 and 21 months after the operations, respectively. Forty-two point four percent (81/191) of the cases treated by arthrotomy did not show any lameness, 29.3% (56/191) showed temporary lameness after rest or heavy exercise, and 28.3% (54/191) showed constant lameness. The signs of which had, however, been reduced by surgery in 14 of these cases. Sixty point one percent (143/238) of the cases treated by arthroscopy did not show any lameness, 29.4% (70/238) showed temporary lameness after rest or heavy exercise and 10.5% (25/238) showed constant lameness, out of which four cases had improved after surgery. In the cases treated by arthroscopy, the period of convalescence was shorter. Differences between these methods were not observed with respect to the development of subsequent arthrosis. The results of the study show that arthroscopy, with its minimal invasive character, gives better functional results than conventional arthrotomy. However, the development of secondary arthrosis cannot be avoided by either method.
The use of Ellis pins (negative profile tip-threaded pins) in external skeletal fixation in dogs and cats
Authors: Pead M. J. , Beck A. L.
Published: March 2018

The Ellis pin is commonly used in external skeletal fixators (ESFs) but some authors suggest that this pin suffers from a high rate of failure. The purpose of this study was to look for complications associated with four different pin types, in particular pin breakage, as well as pin loosening, radiolucency around pins and pin tract discharge. Fifty consecutive cases which had an ESF applied using Ellis pins were identified. Radiographs and case records were used to record case details, ESF design, duration of fixation, pin types used, and complications. Records from 31 dogs and 17 cats were examined (2 animals were removed from the study because of incomplete follow-up). There were 21 Type I, 7 Type I with a tied-in IM pin, 2 modified Type I, 2 modified Type I with a tied-in IM pin and 16 modified Type II ESFs. 160 Ellis pins, 30 centrally threaded positive profile pins, 4 end threaded positive profile pins and 46 smooth pins were used. Complications relating to one or more of the pins were seen in 65% of the fixators. None of the pins broke. There was a significant association between individual pin type and the number of pins showing loosening (p = 0.002) or radiolucency (p = 0.006), but not a significance in the association between pin type and discharge (Chi-Square test). When each pin was compared against each other pin, smooth pins were significantly more likely to be loose than Ellis pins (p <0.001), and centrally threaded positive profile pins were significantly more likely to result in radiolucency than Ellis pins (p = 0.01), using a Chi-square test. There was not any significant association between any other pin types for any complication using a Fisher’s Exact test. The study demonstrates that Ellis pins, when inserted correctly, are not at any greater risk of failure than other pin types, and that fewer complications may be associated with them than other pin designs.
Effect of weight bearing on the joint angles of the fore- and hind limb of the dog
Authors: Rochat M. , Payton M. , Watson C.
Published: March 2018

In the dog the correct angles for arthrodesis of limb joints have been published in the veterinary literature. They can also be obtained by measuring the joint angles of the contralateral limb from a standing lateral radiograph. This study was undertaken to determine if increased weight-bearing had a significant effect on joint angles. Standing lateral radiographs of the foreand hind limbs were taken of dogs standing on all four legs and then with their contralateral limb elevated. A significant difference was found between the angles of the metacarpophalangeal and metatarsophalangeal joints (p ≤ 0.05) when the dog was bearing weight on all four limbs compared to when the contralateral limb was elevated. Significant differences were not found for the other joints that were evaluated (shoulder, elbow, antebrachial carpal, stifle tibiotarsal).
The Cranial Rectus Abdominus Muscle Pedicle Flap in the Dog
Authors: Bauer M. S. , Steyn P.F. , Toombs Wanda , Orton E.C. , Degner D. A.
Published: March 2018

The cranial rectus abdominus muscle pedicle flap (CRAMP) group did not demonstrate any significant difference in perfusion compared to the control rectus abdominus muscle flap group with the caudal epigastric artery intact. Angiography of the cranial epigastric artery demonstrated anastomoses with the caudal epigastric artery.

This study evaluated the angio-gram of the cranial epigastric artery and perfusion of the cranial rectus abdominus muscle pedicle (CRAMP) flap using scintigraphy. The results indicated the CRAMP flap may remain viable in a chronic model.
Biomechanical Properties of Ethylene Oxide Sterilized and Cryopreserved Cortical Bone Allografts
Authors: van Bree H. , Mattheeuws D. , Tshamala M.
Published: March 2018

To evaluate changes during preservation, 76 femoral segments of cortical bone of dogs were tested biomechanically in order to determine their strength in compression, in bending and in torsion. These bones were wrapped in plastic-paper and they were sterilized with ethylene oxide 12%, at 30° C and 1.4 bars and preserved thereafter at 舑20° C. According to the applied loading test, three treatment groups were devised; each treatment group was subdivided into five groups: one control (fresh specimen) and four test-groups differing from each other by the preservation time; i.e. 3, 6, 9 or 12 months. Statistical analysis has demonstrated that there is not a significant difference between the test results for each test-group and its control. The conclusion of this study was that bones, treated as described above, can be stored up to one year without risks to significantly reduce their strength in compression, in bending and in torsion.

To evaluate changes during preservation, femoral segments of cortical bone of dogs were tested biomechanically in order to evaluate their resistance in compression, in bending and to twisting moments. These bones were wrapped in plastic-paper and they were sterilized with ethylene oxide 12%, at 30° C and 1.4 bars and preserved thereafter at -20 ° C. Statistical analysis has shown that there was not a significant difference between the test results for each test-group and its control. As a conclusion, bone allografts, treated as described above, can be stored up to one year without risks to reduce significantly, their resistance to compressive, bending and torsional loads.
The Mini Instrument and Implant Set and its Clinical Application
Authors: Pohler Ortrun E.M. , Olmstead M. L. , Wendelburg K. L. , Montavon P. M.
Published: March 2018

AO-ASIF methods and principles for fracture repair in small animal surgery are expanded with the use of the Mini Instrument and Implant Set. The technical characteristics of this fixation system, including Mini Plates particularly developed for the small animal patient, are presented. Three categories of clinical applications for the small size implants are reviewed and illustrated with clinical case reports. They include: (a) long bone fractures in patients under 5 kg, (b) articular fractures, (c) small bone fractures in larger dogs.
Stabilization of Canine Pelvic Osteotomies with AO/ASIF Plates and Screws
Authors: Hunt C.A. , Litsky A S.
Published: March 2018

Stabilization of pelvic osteotomy with a 2.7 mm dynamic compression plate (DCP) for the treatment of hip dysplasia, was performed in 42 operations in 27 dogs. Screw loosening was observed in 11 osteotomies (26%), plate bending in six cases (14%) and plate breakage in two cases (4%). An in vitro experiment using the pelvic bones of young mixed breed dogs showed no significant difference in the holding power of AO/ASIF 2.7 mm cortical, 3.5 mm cortical and 3.5 mm fully threaded cancellous screws in the body of the ilium. The 2.7 mm DCP has an advantage over the 3.5 DCP in stabilizing pelvic osteotomy because it allows more screws to be used per unit length of plate, which possibly results in a more stable fixation.
The Sensitivity and Specificity of Radiology and Histopathology in the Diagnosis of Posttraumatic Osteomyelitis
Authors: Tvedten H. W. , Mostosky U. V. , Thomas M. , Stickle R. L. , Kaneene J. B. , Braden T. D.
Published: March 2018

The sensitivity and specificity of radiology and histopathology in the diagnosis of post-traumatic osteomyelitis was determined. Post-traumatic osteomyelitis was created in one tibia of each of 31 dogs. Fifteen dogs did not receive treatment and sixteen dogs were treated with clindamycin (11 mg/kg body weight q 12 h, PO) for 28 days. At 8 wks post-inoculation week, S. aureus was isolated from nine of 31 dogs. Bacteriological reculture was the standard diagnostic test for osteomyelitis and was used as the standard for comparison in the calculations of the sensitivity and specificity of both radiology and histopathology. The sensitivity of radiology (radiological consensus of three radiologists) in the diagnosis of post-traumatic osteomyelitis at 8 weeks post-inoculation was 62.5% with a range among individual radiologists from 37.5% to 62.5%. The specificity of radiology (consensus) in the diagnosis of posttraumatic osteomyelitis at 8 weeks post-inoculation was 57.1% with a range among individual radiologists from 28.5% to 95.2%. The sensitivity of histopathology in the diagnosis of post-traumatic osteomyelitis at 8 weeks post-inoculation was 33.3%. The specificity of histopathology in the diagnosis of post-traumatic osteomyelitis at 8 weeks post-inoculation was 86.3%.
Secondary Fractures Following Internal Fixation in Two Horses
Authors: Gaughan E. M. , Duchar N. G.
Published: March 2018

Implant associated fractures have not been reported in horses. Two horses were evaluated for fractures in the fore limbs, occurring subsequent to previous fracture repair. Previously, the horses had sustained fractures of unusual configurations which were repaired using internal fixation. Following repair and healing of the fractures, secondary fractures occurred in the same bone, but in a different (more common) configuration. The first horse was evaluated ten months following lag screw fixation of a longitudinal fracture of the proximal phalanx in a frontal plane. This horse presented with a more typical comminuted fracture in the sagittal plane with the screws from the first fixation lying in the fracture line. This fracture was successfully treated with a cast. The second horse was examined eightteen months after repair of a medial sagittal slab fracture of the third carpal bone. The horse presented with a more typical dorsal slab fracture of the third carpal bone with the previously placed lag screw lying in the fracture line. The screw was removed and a lag screw was placed perpendicular to the new fracture plane through the dorsal surface of the third carpal bone to repair the fracture.
Extended Use of the Caudal Superficial Epigastric Arterial Pedicle Graft in the Dog
Authors: Walshaw R. A. , Johnston S. A.
Published: March 2018

A caudal superficial epigastric arterial pedicle graft was used to cover a large skin defect of the lateral hind quarters in two dogs. The grafts were used to provide durable skin, allow mobility of the patient, and correct a wound contracture deformity. The successful use of the caudal superficial epigastric arterial pedicle graft over lateral hind quarter defects has not previously been reported and demonstrates its mobility and applicability in animals suffering skin loss injuries in this region.
Comparison of Cerclage Wire Placement in Relation to a Neutralization Plate: A Mechanical and Histological Study
Authors: Schwarz P. D. , Powers Barbara , Histand M. E. , Willer R. L.
Published: March 2018

An oblique femoral osteotomy model was created to determine if placement of cerclage wires, in relation to a neutralization plate (under vs over), affects bone healing and mechanical strength. In phase I of the study, femora of five skeletally mature mixed breed dogs were stabilized with a neutralization plate and three cerclage wires. One femur from each dog had the cerclage wires placed under the plate and the opposite femur had the cerclage wires placed over the plate. One dog was eliminated from the study due to nonunion. At eight weeks, the osteotomy sites were subjected to a torsional load and studied histologically. In phase II, 40 pairs of femora were used to determine whether cerclage wire placement and size affected the mechanical strength of the bone-plate model when torsional loads were applied. Within the limits explored in this study, placement of cerclage wires under the plate resulted in an osteotomy which was more resistant to torsional loads and was more advanced histologically towards bone healing. Cerclage wires placed under the plate appeared to provide improved osteotomy stabilization. Cerclage wire size did not significantly influence the mechanical strength of the bone-plate model.

The comparison of cerclage wire placement in relation to a neutralization plate, using an oblique femoral osteotomy model, is discussed. Resistance to torsional loads was greater in eight week healed osteotomies when the cerclage wires had been placed under versus over a neutralization plate.
The Anatomy Heresies Continued VI
Authors: Shively M. J.
Published: March 2018

This essay presents incorrect, misleading, or easily misconstructed anatomical statements from a number of sources and follows each with editorial and clinically applicable commentary. The purpose of this exercise is not to degrade the sources, but only to correct the misconceptions in an attempt to avoid their perpetuation.
Time Course of ECG Depolarization and Repolarization Changes during Ischemia in PTCA Recordings
Authors: García J. , Wagner G. , Bailón R. , Sörnmo L. , Laguna P. , Pueyo E.
Published: March 2018

Objectives:
In this work we studied the temporal evolution of changes in the electrocardiogram (ECG) as a consequence of the induced ischemia during prolonged coronary angioplasty, comparing the time course of indexes reflecting depolarization and those reflecting repolarization.

Methods:
We considered both local (measured at specific points of the ECG) and global (obtained from the Karhunen-Loève transform) indexes. In particular, the evolution of Q, R and S wave amplitudes during ischemia was analyzed with respect to classical indexes such as ST level. As a measurement of sensitivity we used an Ischemic Changes Sensor (ICS), which reflects the capacity of an index to detect changes in the ECG.

Results:
The results showed that, in leads with low-amplitude ST-T complexes, the S wave amplitude was more sensitive in detecting ischemia than was the commonly used index ST60. It was found that in such leads the S wave amplitude initially exhibited a delayed response to ischemia when compared to ST60, but its performance was better from the second minute of occlusion. The global indexes describing the ST-T complex were, in terms of the ICS, superior to the S wave amplitude for ischemia detection.

Conclusions:
Ischemic ECG changes occur both at repolarization and depolarization, with alterations in the depolarization period appearing later in time. Local indexes are less sensitive to ischemia than global ones.
A Nonlinear Circuit Architecture for Magnetoencephalographic Signal Analysis
Authors: Fortuna L. , Frasca M. , Rosa M. , Virzì M. C. , Shannahoff-Khalsa D. , Bucolo M.
Published: March 2018

Objectives:
The objective of this paper was to face the complex spatio-temporal dynamics shown by Magnetoencephalography (MEG) data by applying a nonlinear distributed approach for the Blind Sources Separation. The effort was to characterize and differentiate the phases of a yogic respiratory exercise used in the treatment of obsessive compulsive disorders.

Methods:
The patient performed a precise respiratory protocol, at one breath per minute for 31 minutes, with 10 minutes resting phase before and after. The two steps of classical Independent Component Approach have been performed by using a Cellular Neural Network with two sets of templates. The choice of the couple of suitable templates has been carried out using genetic algorithm optimization techniques.

Results:
Performing BSS with a nonlinear distributed approach, the outputs of the CNN have been compared to the ICA ones. In all the protocol phases, the main components founded with CNN have similar trends compared with that ones obtained with ICA. Moreover, using this distributed approach, a spatial location has been associated to each component.

Conclusions:
To underline the spatio-temporal and the nonlinearly of the neural process a distributed nonlinear architecture has been proposed. This strategy has been designed in order to overcome the hypothesis of linear combination among the sources signals, that is characteristic of the ICA approach, taking advantage of the spatial information.
Automatic Paroxysmal Atrial Fibrillation Based on not Fibrillating ECGs
Authors: Mota S. , Toro F. J. , Díaz A. F. , Fernández F. J. , Ros E.
Published: March 2018

Objectives:
The objective of the paper is to describe an automatic algorithm for Paroxysmal Atrial Fibrillation (PAF) Detection, based on parameters extracted from ECG traces with no atrial fibrillation episode. The modular automatic classification algorithm for PAF diagnosis is developed and evaluated with different parameter configurations.

Methods:
The database used in this study was provided by Physiobank for The Computers in Cardiology Challenge 2001. Each ECG file in this database was translated into a 48 parameter vector. The modular classification algorithm used for PAF diagnosis was based on the nearest K-neighbours. Several configuration options were evaluated to optimize the classification performance.

Results:
Different configurations of the proposed modular classification algorithm were tested. The uni-parametric approach achieved a top classification rate value of 76%. A multi-parametric approach was configured using the 5 parameters with highest discrimination power, and a top classification rate of 80% was achieved; different functions to typify the parameters were tested. Finally, two automatic parametric scanning strategies, Forward and Backward methods, were adopted. The results obtained with these approaches achieved a top classification rate of 92%.

Conclusions:
A modular classification algorithm based on the nearest K-neighbours was designed. The classification performance of the algorithm was evaluated using different parameter configurations, typification functions and number of K-neighbors. The automatic parametric scanning techniques achieved much better results than previously tested configurations.
Accurate Volumetric Measurements of Anatomical Cavities
Authors: Orman J. , Gürvit Ö. , Bartz D.
Published: March 2018

Objectives:
The volumetric assessment of anatomical cavities is of high relevance for various applications in medicine. Based on 3D scanning (i.e., CT) of these cavities, the volume can be determined by counting the volume elements of a segmentation of that cavity. Unfortunately, elements on the boundary of the segmentation require special treatment to obtain accurate volumetric measurements. In this paper, we propose a novel technique that in particular increases the accuracy of the volume estimation for the boundary elements of segmented anatomical objects.

Methods:
Based on a 3D segmentation of an anatomical cavity, we recursively subdivide boundary volume elements into a set of simple situations, where the volume can be estimated easily.

Results:
We performed volumetric measurements on seven datasets of phantom models made of plexiglass (see Fig. 1) scanned by a biplane angiography unit and assessed the quality of our method by comparing the measured volume by our novel method and by the fluid required to fill the phantom cavities.

Conclusions:
Our method calculates a significantly more accurate volume of the segmented cavities than previous methods. Nevertheless, it is only slightly more computationally expensive.
Sample Size Calculations for Controlled Clinical Trials Using Generalized Estimating Equations (GEE)
Authors: Rochon J. , König I. R. , Ziegler A. , Dahmen G.
Published: March 2018

Objectives:
Clinical trials with correlated response data based on generalized estimating equations (GEE) have become increasingly popular as they require smaller samples than classical methods that ignore the clustered nature of the data. We have recently derived the recommendation to use the independence estimating equations (IEE) as primary analysis in most controlled clinical trials instead of GEE with estimated correlations [1]. Although several approaches for sample size and power calculation have been proposed, we have shown that most of these procedures are very specific and not as general as required for designing clinical trials.

Methods:
We extended the previously developed SAS macro GEESIZE to overcome this restriction. Specifically, we have added the option of an independence working correlation matrix required for the IEE. Additionally, we have reformulated the hypotheses to allow for coding that includes an intercept term instead of the previously used analysis of variance coding.

Results:
To demonstrate the validity of GEESIZE we investigate the calculated sample sizes for specific models where closed formulae are available. For illustration, we utilize GEESIZE for planning a new trial on the treatment of hypertension and thereby exemplify its flexibility.

Conclusions:
We show that our freely available macro is a very general and useful tool for sample size calculation purposes in clinical trials with correlated data.
A Simulation Model for Small-area Cancer Incidence Rates
Authors: Daugs A. , Meyer M. , Radespiel-Tröger M.
Published: March 2018

Objectives:
Cancer epidemiologists are often asked by members of the interested public about possible associations between suspected carcinogens and apparently increased small-area cancer incidence rates. Frequently, no systematic incidence differences can be demonstrated. Nevertheless, it is necessary to address public concerns about suspected cancer clusters. To facilitate explanations about the large random variation of small-area tumor incidence, we implemented a software simulation tool in R.

Methods:
Under the assumption of no cancer causes other than chance, the tool simulates a small village population with an average number of five inhabitants per house and allows graphical visualisation of ten streets with 100 houses. Published age-specific incidence and mortality data are used for event sampling based on the binomial distribution. Program parameters include sample size, age distribution, cancer incidence, and mortality rates.

Results:
On average, 22 percent (2.2/10) of all houses per street have been inhabited by at least one cancer patient during the last five years in our simulated small village. A situation where all (10) houses in a street have been inhabited by at least one cancer patient during the last five years appears to be very rare (less than one in a million streets).

Conclusions:
Our software tool can be used effectively for numerical and graphical visualisation of small-area tumour incidence and prevalence rates due to chance alone. The explanation of basic epidemiological concepts to members of the public can help to increase public motivation and support for population-based cancer registration. Our simulation tool can be used to support this goal.
Annoyance from Multiple Transportation Noise: Statistical Models and Outlier Detection
Authors: Schürmann C. , Griefahn B. , Kuhnt S.
Published: March 2018

Objective:
Statistical models for the annoyance from multiple transportation noise are needed to understand and predict the annoyance resulting from specific noise exposures.

Methods:
Models from the class of generalized linear models are suggested and discussed. Observations which are not well explained by the considered model are regarded as outliers. Outlier detection methods are applied to the data modelled by robust estimates using different link functions.

Results:
The discussed methods are applied to data from a laboratory experiment using generalized linear models. While considering outliers, a generalized linear model with a complementary log-log link is found to be a good choice in modelling the exposure-response relationship between noise levels and annoyance.
An Implementation of Automated Individual Matching for Observational Studies
Authors: Hüsing J. , Jöckel K.-H. , Schröder M.
Published: March 2018

Objectives:
Individual matching is frequently used in observational studies. Its main purpose lies in efficiency of study conduct and parameter estimation. Ideally, an individually matched index subject differs from the reference subject(s) only by the factor(s) of interest. Matching is used to select comparable subgroups on which further data analysis can then concentrate. Finding optimal subsets is then a closed problem, which may include a lot of guesswork. It is a task that begs an algorithmic solution that can be obtained automatically.

Methods:
The problem can be formalized as a minimization of a global loss function that summarizes the deviation from perfect agreement over different variables. Through the representation by a network formed by a bipartite graph of index and reference subjects, one can obtain a solution by finding a minimum cost flow in a certain network. We have implemented a Web-based application using the efficient CS2 algorithm.

Results:
Variations of the individual matching procedures that have been implemented comprise 1:N matching and matching with a variable number of controls. The user can upload own data, view the proposed result in a list and finally download the matching plan. Representation of quality of individual matches as background colors allows rapid checks for overall matching accuracy.

Conclusions:
The computer-assisted variation reduces the human interaction to the tuning of a few parameters, rather than individual decisions on forming separate matches. This not only saves a lot of work but also simplifies communicating the matching process. The program addresses a general class of matching problems. The use of this tool for special cases of matching, as caliper matching or exact category matching, is highlighted.
Gene Methylation Data – a New Challenge for Bioinformaticians?
Authors: Müller H. M. , Fiegl H. , Widschwendter M. , Goebel G.
Published: March 2018

Objectives:
Changes in the status of DNA methylation, known as epigenetic alterations, are among the most common molecular alterations in human neoplasia. For the first time, we reported on the analysis of fecal DNA from patients with CRC to determine the feasibility, sensitivity and specificity of this approach. We want to present basic information about DNA methylation analysis in the context of bioinformatics, the study design and several statistical experiences with gene methylation data. Additionally we outline chances and new research questions in the field of DNA methylation.

Methods:
We present current approaches to DNA methylation analysis based on one reference study. Its study design and the statistical analysis is reflected in the context of biomarker development. Finally we outline perspectives and research questions for statisticians and bioinformaticians.

Results:
Identification of at least three genes as potential DNA methylation-based tumor marker genes (SFRP2, SFRP5, PGR).

Conclusions:
DNA methylation analysis is a rising topic in molecular genetics. Gene methylation will push the extension of biobanks to include new types of genetic data. Study design and statistical methods for the detection of methylation biomarkers must be improved. For the purpose of establishing methylation analysis as a new diagnostic/prognostic tool the adaptation of several approaches has become a challenging field of research activity.
On Exemplary Scientific Conduct Regarding Submission of Manuscripts to Biomedical Informatics Journals
Authors: Groth T. , Hasman A. , Safran C. , Shortliffe E. H. , Haux R. , McCray A. T. , Miller R. A.
Published: March 2018

As the Editors of leading international biomedical informatics journals, the authors report on a recent pattern of improper manuscript submissions to journals in our field. As a guide for future authors, we describe ethical and pragmatic issues related to submitting work for peer-reviewed journal publication. We propose a coordinated approach to the problem that our respective journals will follow. This Editorial is being jointly published in the following journals represented by the authors: Computer Methods and Programs in Biomedicine, International Journal of Medical Informatics, Journal of Biomedical Informatics, Journal of the American Medical Informatics Association, and Methods of Information in Medicine.
Mapping OpenSDE Domain Models to SNOMED CT
Authors: Baofen Ding , Weeber M. , van Ginneken A. M. , Min Zhu
Published: March 2018

Objectives:
To explore the strengths and pitfalls of mapping structured EPR (electronic patient record) terms (OpenSDE) to SNOMED codes.

Methods:
The OpenSDE model was developed for cardiovascular diseases in the context of the I4C project. We employed 35 patient records as references to adjust the model. We then performed automated and manual matches following the design of matching terms in the thesaurus of the resulting OpenSDE domain model to SNOMED concepts. Subsequently, we assessed what number of OpenSDE terms within the domain model can be matched to SNOMED concepts.

Results:
The OpenSDE domain tree contains 3230 nodes, involving 689 unique terms (terms can be associated with more than one node in different parts of a domain model tree). After final manual work for the 689 tree terms, 616 resulted in a good match, 31 in a partial match, and 42 in no match. Of the good matches, 23 produced multiple matches. The matches were used to represent the mapping of each node in the domain tree by concatenation of the matching terms.

Conclusions:
Mapping predefined terms in OpenSDE domain models to SNOMED Clinical Terms (CT) concepts eliminates laborious mapping for each individual patient record. The assignment of SNOMED codes to OpenSDE tree nodes facilitates exchange, aggregation, and research involving patient data. The mapping will serve the construction of queries at higher semantic levels than explicitly modeled in an OpenSDE domain model. However, the usefulness of the mapping result depends on the completeness of the mapping to SNOMED CT, for which there is no gold standard.
A Scoring System for Ascertainment of Incident Stroke; the Risk Index Score (RISc)
Authors: Moyé L. A. , Smith M. A. , Morgenstern L. B. , Kass-Hout T. A.
Published: March 2018

Objectives:
The main objective of this study was to develop and validate a computer-based statistical algorithm that could be translated into a simple scoring system in order to ascertain incident stroke cases using hospital admission medical records data.

Methods:
The Risk Index Score (RISc) algorithm was developed using data collected prospectively by the Brain Attack Surveillance in Corpus Christi (BASIC) project, 2000. The validity of RISc was evaluated by estimating the concordance of scoring system stroke ascertainment to stroke ascertainment by physician and/or abstractor review of hospital admission records.

Results:
RISc was developed on 1718 randomly selected patients (training set) and then statistically validated on an independent sample of 858 patients (validation set). A multivariable logistic model was used to develop RISc and subsequently evaluated by goodness-of-fit and receiver operating characteristic (ROC) analyses. The higher the value of RISc, the higher the patient’s risk of potential stroke. The study showed RISc was well calibrated and discriminated those who had potential stroke from those that did not on initial screening.

Conclusion:
In this study we developed and validated a rapid, easy, efficient, and accurate method to ascertain incident stroke cases from routine hospital admission records for epidemiologic investigations. Validation of this scoring system was achieved statistically; however, clinical validation in a community hospital setting is warranted.
PACS Development in Austria: A Discussion of Success Criteria and Success Factors
Authors: Gell G.
Published: March 2018

Objectives:
The paper uses the example of PACS (Picture Archiving and Communication System) in Austria (where some of the earliest large PACS projects were realised and led to a high penetration with state-wide networked PACS installations) to discuss success criteria and success factors of medical information systems.

Methods:
The paper describes the development of digital imaging in medicine and classifies the impact of systems according to their first or second order effects on patient care. The historic goals of PACS and the technical infrastructure in the eighties are shortly described.

The paper then outlines the early PACS projects in Austria and their different approaches as well as the present state of PACS in Austria.

Results:
After giving a definition of success, success criteria (which allow to decide whether a system is in fact a success or not) are discussed in general – the final criterion being routine use – and in detail and it is concluded that PACS in Austria was and is indeed successful.

Conclusion:
The analysis of success factors shows a multitude of influences but the most decisive ones are the practical ability of the system to deliver a real service to health care and the ability to support the (key) users in their work and goals.
Implementation of Health Information Systems in Romania
Authors: Bazavan M. , Farcas D. D. , Mihalas G. I.
Published: March 2018

Objectives:
The paper aimed to present and analyze the development of Healthcare Information Systems in Romania during the last decade. The first part was dedicated to the analysis of a large national project, HMIS – Healthcare Management Information System, and the second to the current state of the hospital information systems and primary care systems.

Methods:
The approach of a “case study” was used. The description of the HMIS project comprised the objectives and its structure, implementation, results and lessons learned. This is followed by a classical short presentation of the current state at the hospital and primary care levels.

Results:
The very modest results of the HMIS project were critically analyzed, listing the ‘failure factors’ at various moments, both weak points of the project as well as the consequences of the structural-organizational changes within the Romanian healthcare system during the implementation. However, mainly positive results were registered in the last years at lower levels, hospitals and primary care, which can also partially be interpreted as ‘lesson learned’.

Conclusions:
There are several things to be learned from the Romanian experience. Healthcare information system analysis is quite complex. Obtaining better results requires several additional measures including better education and training, adopting standards and appropriate quality assessment tools.
Standardized Exchange of Clinical Documents
Authors: Müller S. , Jablonski S. , Prokosch H.-U. , Gerdsen F.
Published: March 2018

Objectives:
The exchange of medical data from research and clinical routine across institutional borders is essential to establish an integrated healthcare platform. In this project we want to realize the standardized exchange of medical data between different healthcare institutions to implement an integrated and interoperable information system supporting clinical treatment and research of glaucoma.

Methods:
The central point of our concept is a standardized communication model based on the Clinical Document Architecture (CDA). Further, a communication concept between different health care institutions applying the developed document model has been defined.

Results:
With our project we have been able to prove that standardized communication between an Electronic Medical Record (EMR), an Electronic Health Record (EHR) and the Erlanger Glaucoma Register (EGR) based on the established conceptual models, which rely on CDA rel.1 level 1 and SCIPHOX, could be implemented. The HL7-tool-based deduction of a suitable CDA rel.2 compliant schema showed significant differences when compared with the manually created schema. Finally fundamental requirements, which have to be implemented for an integrated health care platform, have been identified.

Conclusions:
An interoperable information system can enhance both clinical treatment and research projects. By automatically transferring screening findings from a glaucoma research project to the electronic medical record of our ophthalmology clinic, clinicians could benefit from the availability of a longitudinal patient record. The CDA as a standard for exchanging clinical documents has demonstrated its potential to enhance interoperability within a future shared care paradigm.
A CORBA-Based Object Framework with Patient Identification Translation and Dynamic Linking
Authors: Ohe K. , Wang C.
Published: March 2018

Exchanging and integration of patient data across heterogeneous databases and institutional boundaries offers many problems. We focused on two issues: (1) how to identify identical patients between different systems and institutions while lacking universal patient identifiers; and (2) how to link patient data across heterogeneous databases and institutional boundaries. To solve these problems, we created a patient identification (ID) translation model and a dynamic linking method in the Common Object Request Broker Architecture (CORBA) environment. The algorithm for the patient ID translation is based on patient attribute matching plus computer-based human checking; the method for dynamic linking is temporal mapping. By implementing these methods into computer systems with help of the distributed object computing technology, we built a prototype of a CORBA-based object framework in which the patient ID translation and dynamic linking methods were embedded. Our experiments with a Web-based user interface using the object framework and dynamic linking through the object framework were successful. These methods are important for exchanging and integrating patient data across heterogeneous databases and institutional boundaries.
Computer-Supported Diagnosis of Melanoma in Profilometry
Authors: Roß Th. , Kreusch J. , Wolff H. H. , Pöppl S. J. , Handels H.
Published: March 2018

Laser profilometry offers new possibilities to improve non-invasive tumor diagnostics in dermatology. In this paper, a new approach to computer-supported analysis and interpretation of high-resolution skin-surface profiles of melanomas and nevocellular nevi is presented. Image analysis methods are used to describe the profile‘s structures by texture parameters based on co-occurrence matrices, features extracted from the Fourier power spectrum, and fractal features. Different feature selection strategies, including genetic algorithms, are applied to determine the best possible subsets of features for the classification task. Several architectures of multilayer perceptrons with error back-propagation as learning paradigm are trained for the automatic recognition of melanomas and nevi. Furthermore, network-pruning algorithms are applied to optimize the network topology. In the study, the best neural classifier showed an error rate of 4.5% and was obtained after network pruning. The smallest error rate in all, of 2.3%, was achieved with nearest neighbor classification.
A Computer-Assisted Drug Prescription System: the Model and its Implementation in the ATM Knowledge Base
Authors: Pouliquen B. , Le Beux P. , Riou C.
Published: March 2018

Informatisation of drug prescription is an important topic in medical informatics. For several years now, computerized drug databases have been implemented. Usually only a small part of the prescriptions can be stored in prescription systems because of the format of the included information; prescriptions contain essentially free text without any structure and homogeneity of the used vocabulary.

In this article a model is presented for knowledge representation in a computerized drug prescription system. The model should be applicable to clinical practice and be didactic for medical students. The problem of standardization of terminology had to be solved. A computer-assisted drug prescription program has been developed. The next step is its validation by clinicians. The program can also be used in a consultation mode.
The Number of Independent Signals in Body Surface Maps
Authors: Uijen G. , van Oosterom A. , Hoekema R.
Published: March 2018

This paper reports on the number of independent signals in body surface maps measured using a variety of lead systems incorporating 32 up to 219 leads. The number of independent signals is estimated using the minimum description length. It is found that the number of independent signals in body surface maps is of the order of 10. For lead systems incorporating many leads the number of independent signals is only marginally larger than in lead systems incorporating fewer leads. A lead system incorporating 64 leads will suffice for most applications.
Semi-Automatic Generation of Medical Tele-Expert Opinion for Primary Care Physician
Authors: Rihl J. , Schenker M. , Standl E. , Biermann E.
Published: March 2018

Objectives: A computer-based system has been developed for the generation of medical expert opinions on the insulin-resistance syndrome, based on clinical data obtained from primary care physicians.

Methods: An expert opinion for each patient was generated by using a decision tree for entering individual text modules and by adding optional free text. The expert opinions were returned by e-mail, telefax or by ordinary mail.

Results: 1389 primary care physician sent anonymous data sets and requested expert opinions for a total of 3768 patients. Through the set up of a rule-based system an automation of the generation of the expert opinions could be achieved and the generation time dropped from initially 40 minutes to less than 5 minutes at the end.

Conclusions: By using predefined text modules and a rule based system, a large number of medical expert opinions can be generated with relatively few additional resources.
Considerations for the Representation of Meta-Data for the Support of Structured Data Entry
Authors: van Ginneken A. M.
Published: March 2018

Objectives: Research and decision support require patient data to be structured. Flexible data representation, to cope with expansion and new recording demands, can be achieved through abstraction of the data model. Such a model, however, does not include explicit information for the support of structured data entry (SDE), i.e. the definition of what is relevant to say in a specific context. The objective of this paper is to provide considerations for an intuitive conceptual representation of such meta-data for domain experts.

Methods: The content of meta-data for SDE is compared with that of controlled medical terminologies in the context of its purpose.

Results: Upon analysis of medical descriptions, a network and a tree both emerge as an intuitive structure to represent meta-data for the support of SDE. The pros and cons of a tree versus a network are dominated by the challenges of representing multiple contexts for description. Meta-data for SDE only partially overlap with the content of controlled medical terminologies.

Conclusions: Integration of meta-data for SDE and controlled terminologies would benefit standardization and retrieval, but the requirements for flexible data entry are at odds with the rigidity and limited granularity of a standard. The preferred strategy seems to be a mapping between the concepts from a terminology standard and meta-data for SDE.
Mutual Information as an Index of Diagnostic Test Performance
Authors: Benish W. A.
Published: March 2018

Objectives: This paper demonstrates that diagnostic test performance can be quantified as the average amount of information the test result (R) provides about the disease state (D).

Methods: A fundamental concept of information theory, mutual information, is directly applicable to this problem. This statistic quantifies the amount of information that one random variable contains about another random variable. Prior to performing a diagnostic test, R and D are random variables. Hence, their mutual information, I(D;R), is the amount of information that R provides about D.

Results: I(D;R) is a function of both 1) the pretest probabilities of the disease state and 2) the set of conditional probabilities relating each possible test result to each possible disease state. The area under the receiver operating characteristic curve (AUC) is a popular measure of diagnostic test performance which, in contrast to I(D;R), is independent of the pretest probabilities; it is a function of only the set of conditional probabilities. The AUC is not a measure of diagnostic information.

Conclusions: Because I(D;R) is dependent upon pretest probabilities, knowledge of the setting in which a diagnostic test is employed is a necessary condition for quantifying the amount of information it provides. Advantages of I(D;R) over the AUC are that it can be calculated without invoking an arbitrary curve fitting routine, it is applicable to situations in which multiple diagnoses are under consideration, and it quantifies test performance in meaningful units (bits of information).