bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel technique of taking tendon biopsies in the horse
Authors: Becker C. K. , Enzerink E. , Spek E. R. , Van Weeren P. R. , Cherdchutham W.
Published: March 2018

To evaluate a novel tendon biopsy technique for use in the horse and to assess the effect of different exercise levels on the healing process of minimally damaged superficial digital flexor tendons (SDFT), 24 Dutch Warmblood foals were randomly divided into 3 equally sized groups one week after birth. One group was box rested, one group got box rest with additional enforced exercise, and one group got free pasture exercise. Biopsies from the peripheral region of the SDFT were taken at age 2 months using a new micro-biopsy technique. At age 5 months the foals were euthanized and samples from the biopsy site and a control site were harvested. Collagen fibrillar index (CFI, the total amount of collagen as a percentage of the measured area), mass-average diameter (MAvD, mean of the diameter versus area distribution) and collagen fibrillar diameter frequency (the distribution of collagen fibril sizes expressed as a percentage of the number of collagen fibrils) were calculated. The CFI, MAvD values were significantly lower in the wound samples. It is concluded that the biopsy technique may be a useful tool for research applications. The absence of exercise-induced effects on the collagen fibril population in the wound samples suggests that the first phase of the process of tendon healing in immature equine SDFT’s sustaining a minor surgically-induced wound, is not exercise-dependent. However, findings may be different in mature horses sustaining accidental trauma.

A novel technique to take biopsies from immature equine flexor tendons was developed and used to evaluate the effect of various levels of exercise on the development of the collagen fibril diameter distribution in the resulting wounds. The technique appeared to be minimally invasive, but complication rate was deemed too high for clinical use. There was no effect of exercise on mass average diameter of collagen fibrils, suggesting that the repair process, at least in its initial stage, is exercise-independent.
Central tarsal bone luxation in three non-racing dogs
Authors: Grösslinger K. , Lorinson D.
Published: March 2018

Each of three adult crossbreed dogs suffered a hock injury during regular exercise. A non-weight-bearing lameness and a soft tissue swelling around the tarsus were present in all of them. Additionally dog # 1 on palpation of the calcaneus region exhibited crepitous. Radiographs showed luxation of the central tarsal bone in all three of the animals. Dog # 1 also had a fracture of the calcaneus. Surgical treatment was performed on all of the cases, via a medial surgical approach. The luxated bone was repositioned and attached to the adjacent 4th tarsal bone with a 3.5 mm countersunk lag-screw. The fracture of the calcaneus was stabilized with a 2.7 mm five hole AO-plate. Postoperatively the injured limbs were immobilized with a cast for four to six weeks and exercise was restricted. After cast removal, all of the dogs received physiotherapy. All three hocks regained full function and owners reported normal activity.

The successful treatment of central tarsal bone luxation in three non-racing dogs is reported.
Sagittal plane kinematics and kinetics of the pastern joint during the stance phase of the trot
Authors: Singleton W. H. , Lanovaz J. L. , Prades Marta , Clayton Hilary M.
Published: March 2018

The objectives were to measure sagittal plane kinematics and kinetics of the forelimb pastern joint during the stance phase at the trot. Sagittal plane video (200 Hz) and force (1,000 Hz) recordings were analyzed from four trials of six sound horses trotting in hand. Kinematic and force data were used to calculate net joint moments and joint powers. The pastern joint showed maximal flexion (155.3 ± 11.0°) at 34% stance and maximal extension (190.2 ± 3.8°) at 93% stance. Energy was absorbed on the palmar aspect throughout stance, with peak energy absorption occurring in the second half of the stance. It was concluded that the primary function of the pastern joint was to act as an energy damper.
The use of the computed tomography in the diagnostic protocol of the elbow in the dog: 24 joints
Authors: Biasibetti Martina , Schumacher Annette , Fabiani Michelle , Rovesti Gian
Published: March 2018

The evaluation of the elbow joint is difficult based on clinical and radiographic examinations. The anatomical structures of its articular components are superimposed with standard radiography, often leading to presumptive diagnoses. When the radiographic findings become more suggestive, usually the early phase of the disease has passed and chronic disease has developed. Because computer-generated slices are not hindered by this superimposition, the use of computed tomography may be beneficial in investigating the joint. The purpose of this study was to evaluate if computed tomography could change or better define the diagnosis previously made on the basis of a radiographic examination in 12 client- owned dogs presented for elbow lameness. As a positive control, 12 out of the 24 imaged joints were surgically or arthroscopically explored. The diagnosis based on computed tomography was different or more precisely defined, compared to the radiographic examination, in 46% of the examined joints. Earlier and more complete definition of elbow joint disease may change the therapeutic options and, potentially, the clinical outcome.
Clinical evaluation of denervation of the canine hip joint capsule: a retrospective study of 117 dogs
Authors: Von Scheven C. , Buecker A. , Stopinski T. , Küpper W. , Kinzel S.
Published: March 2018

It was the aim of this study to evaluate denervation of the canine hip joint capsule as a newly developed surgical method for treatment of hip joint dysplasia and arthrosis of dogs. Denervation by surgical deperiostation of the cranio-lateral acetabulum is the presumed mechanism. We performed the denervation in 117 cases between 1997 and 1999. Clinical evaluation was documented by physical examination by a veterinarian immediately before and two months after the operation and a questionnaire completed by the dog owners. 90.6% of the patients showed an improvement of the clinical signs yielding a significant treatment effect (p <0.0001). 50.4% were even completely free of signs. 56% of the patients showed a clinical improvement within the first three days after surgery. We, therefore, conclude that denervation of the canine hip joint capsule is a successful surgical method for treatment of canine hip joint dysplasia and arthrosis.
Fracture of the lesser tuberosity of the humerus in a dog
Authors: Carmichael S. , Clements D. N.
Published: March 2018

This case report describes a traumatic fracture of the lesser tuberosity of the humerus in a one-year-old dog. Conservative management failed to allow healing, and pronounced medial instability of the shoulder and partial rupture of the biceps brachii tendon developed. Tenodesis of the biceps brachii tendon and repair of the fractured lesser tuberosity by lag screw fixation resulted in a complete recovery of limb function.
Aneurysmal bone cyst in the distal radius of a dog: diagnostic imaging and surgical treatment
Authors: Dowdle S.M. , Lambrechts N.E. , Duncan N.M. , Spotswood T.C.
Published: March 2018

An 11 month old, female Golden Retriever was examined for chronic right thoracic limb lameness and progressive swelling of the distal radius. Survey radiographs revealed an expansile, osteolytic lesion in the distal metaphyseal region of the radius consistent with an aneurismal bone cyst. Diagnostic imaging, biopsy, angiography and histopathology supported this diagnosis. The condition was treated by segmental osteotomy of the affected radius, placement of a vascularized autogenous bone graft harvested from the contralateral ulna, and stabilized using a plate that incorporated the carpal joint. The pathogenesis, diagnostic dilemmas and treatment options in dogs and human patients is discussed.
The SK™ external fixation system: description of components, instrumentation, and application techniques
Authors: Bronson D. G. , Ross D. , Welch R. D. , Toombs J. P.
Published: March 2018

The SK™ external fixator was designed to overcome the problems commonly encountered with clinical use of the Kirschner-Ehmer (KE) splint. It enables the use of a range of different fixation pin diameters within a construct, improved pin centering within the bone, increased flexibility in frame construction and disassembly, and a decreased need for the use of full-pins to achieve fracture stabilization. The SK™ external fixator is available in three sizes: mini, small, and large. This report describes the components of the SK™ ESF system, the instrumentation needed to apply it, and the recommended application techniques.
Interlocking Nail Stabilisation of Humeral Fractures. Initial Experience in Seven Clinical Cases
Authors: Diaz M.C. , Morales I. , Durall I.
Published: March 2018

Seven cases of fracture of the humerus were stabilised by interlocking nailing. In six cases fixation was static, and in one dynamic. Healing of the fractures took place within a maximum of 16 weeks and return of functionality was complete within three weeks, with the exception of one case. The complications were: failure to insert the screws in the nail, partial loosening of a screw, and production of a new fracture at the distal end of the nail in the case with dynamic fixation.

Seven humeral fractures were stabilised by interlocking nailing. Healing of bone took place in six cases.

The complications involved were: failure to insert screws in the nail, loosening of the screws, and production of a fresh fracture at the distal end of the nail.
Application of the Dynamic Condylar Screw (DCS)- and Dynamic Hip Screw (DHS) Implant Systems in the Horse
Authors: Auer J. A.
Published: March 2018

The surgical technique for application of the dynamic condylar screw (DCS)- and dynamic hip screw (DHS) implant systems is described and then illustrated by 3 clinical cases. The DCS/DHS system ist stronger and more versatile than the regular DCP or angled blade plate (ABP). This system can be successfully applied for osteotomies and/or fractures of the epiphyseal/metaphyseal region of a longbone in horses. Such fractures are especially difficult to repair because of the small number of implants which can be inserted in the smaller metaphyseal portion of the bone. By using the DCS/DHS system double plating may be unnecessary in selected cases. The combination of the DCS/ DHS system with 5.5 mm diameter cortical bone screws represent ideal implants for internal fixation of longbone fractures and corrective osteotomies in the horse.
Remodeling of Cancellous and Cortical Canine Bone in Response to Decreased Mechanical Loading
Authors: Kamibayashi L. , Hearn T. , Taves C. , Thomason J. J. , Binnington A. G. , Pfeiffer S.
Published: March 2018

Thirteen pairs of tibiae were excised from adult mongrel dogs following a mean recovery period of 24.2 weeks after unilateral total hip arthroplasty (THA). Prior to euthanasia, peak vertical dynamic load, as a percent of body weight, was determined for each limb at a walking pace. Four contiguous proximal sections and one transverse cortical midshaft section, 5mm thick, were harvested from each tibia. Contact Faxitron radiographs of the sections were quantified, using video digitizing software, to compare mean apparent density measures between the treated (THA) and intact limbs. There was a significant difference in mean apparent density of cancellous bone with the treated limb having a lower apparent density than the intact limb. The mean cortical area at the midshaft was significantly lower and the medullary area significantly higher among tibiae from the treated side, as compared to the contra-lateral tibiae. Resistance to bending and tension at the midshaft of each bone were determined using the second moment of area about cranio-caudal (Ix) and mediolateral (Iy) axes. The mean Iy values for the treated limbs were significantly lower than for the intact limbs. Therefore, measurable adaptive bone remodeling appears to be present in both cancellous and cortical bone in the tibia due to decreased mechanical loading.
Interfragmentary Stability Influences Healing of Intra-articular Fractures. A Radiographic Study of Canine Femoral Condyle Fractures Repaired with Lag Screws
Authors: Francis D. J. , Johnson K. A.
Published: March 2018

The influence of fracture stability on the healing of intra-articular fractures of canine medial femoral condyles repaired with lag screws was evaluated radiographically and at necropsy. In 14 dogs, one condylar fracture was repaired with stable interfragmentary compression using two 4.0 mm cancellous lag screws. In the contralateral stifle, the condylar fracture was apposed with a single 4.0 mm cancellous lag screw so that the bone fragments were unstable and had interfragmentary motion. In a control group (n = 4), an arthrotomy was performed and a lag screw inserted without creating a fracture in one stifle. In the contralateral stifle, a condylar fracture was created and not repaired.

Radiographically stable fracture gaps were slightly wider at one month than immediately post repair, but at two and three months were healed completely. Unstable fractures remained incompletely healed at one, two and three months. Osteophytes were detectable radiographically at three months. Unrepaired fractures remained completely unhealed and these joints had severe osteophyte formation at one month. At necropsy, all joints with intra-articular fractures had some osteophytes and erosion of the medial tibial plateau articular cartilage. It was concluded that interfragmentary compression was a critical factor in fracture healing and that lack of stability caused delayed union, osteophyte development and cartilage erosion.

A model was developed to permit the study of the healing of both stable and unstable condyle repair.
Analysis of Vocal Tract Characteristics for Near-term Suicidal Risk Assessment
Authors: Ozdas A. , Wilkes D. M. , Silverman M. K. , Silverman S. E. , Shiavi R. G.
Published: March 2018

Objectives:
Among the many clinical decisions that psychiatrists must make, assessment of a patient’s risk of committing suicide is definitely among the most important, complex and demanding. One of the authors reviewing his clinical experience observed that successful predictions of suicidality were often based on the patient’s voice independent of content. The voices of suicidal patients exhibited unique qualities, which distinguished them from non-suicidal patients. In this study we investigated the discriminating power of lower order mel-cepstral coefficients among suicidal, major depressed, and non-suicidal patients.

Methods:
Our sample consisted of 10 near-term suicidal patients, 10 major depressed patients, and 10 non-depressed control subjects. Gaussian mixtures were employed to model the class distributions of the extracted features.

Results and Conclusions:
As a result of two-sample ML classification analyses, first four mel-cepstral coefficients yielded exceptional classification performance with correct classification scores of 80% between near-term suicidal patients and non-depressed controls, 75% between depressed patients and non-depressed controls, and 80% between near-term suicidal patients and depressed patients.
ECG Analysis for Sleep Apnea Detection
Authors: von Einem V. , Widiger B. , Joseph G. , Zywietz C. W.
Published: March 2018

Objectives:
The objective of our study was to find out whether obstructive sleep apnea (OSA) may be detected on ECGs recorded during sleep.

Methods:
We have analyzed 70 eight-hour single-channel ECG recordings taken at polysomnographia. The 70 data sets were annotated for definition of regular sleep and phases with sleep apnea. From the 70 data sets, 35 have been used as a learning set. Our analysis is based on spectral components of heart rate variability. Frequency analysis was performed using Fourier and wavelet transformation with appropriate application of the Hilbert transform. Classification is based on four frequency bands: ULF band (0-0.013 Hz), VLF band (0.013-0.0375 Hz), LF band (0.0375-0.06 Hz) and the HF band (0.17-0.28 Hz). Linear discriminant functions were applied using mainly spectral components derived from the records. Classification of cases was based on three variables.

Results:
For the Testing Set, a sensitivity (Se) for apnea of 92.3% at a specificity (Sp) of 94.6% was achieved. For the minutes allocation on the Learning Set Se was 90.8% at Sp 92.7%.

Conclusion:
ECG analysis is useful for the detection of sleep apnea and may help to differentiate causes of cardiac arrhythmias.
Independent Component Analysis Compared to Laplacian Filtering as ”Deblurring” Techniques for Event Related Desynchronization/ Synchronization
Authors: Bianchi A. M. , Cincotti F. , Babiloni C. , Carducci F. , Babiloni F. , Rossini P. M. , Cerutti S. , Foffani G.
Published: March 2018

Objectives:
The aim of the work was to compare two different approaches – one model-dependent, the other data-dependent – for “deblurring” EEG data, in order to improve the estimation of Event-Related Desynchronization/Synchronization.

Methods:
Realistic Surface Laplacian filtering (SL) and Infomax Independent Component Analysis (ICA) were applied on multivariate scalp EEG signals (SL: 128 electrodes with MRI-based realistic modeling; ICA: a subset of 19 electrodes, no MRI) prior to beta Event Related Synchronization (ERS) estimation after finger movement in 8 normal subjects. ERS estimation was performed using standard band-pass filtering. ERS peak amplitudes and latencies in the most responsive channel were calculated and the effect of the two methods above was evaluated by one-way analysis of variance (ANOVA) and Sheffe’s test.

Results:
Both methods and their combination significantly improved ERS estimation (greater ERS peak amplitude, p <0.05). The results obtained after ICA on 19 electrodes were not significantly different than the ones obtained with Realistic SL using 128 electrodes and MRI for scalp modeling (p >0.89).

Conclusions:
The “low cost” of ICA (19 electrodes, no MRI) imposes such method as a valid alternative to SL filtering. The employ of ICA after SL filtering suggests that the “ideal EEG deblurring method” would unify the two approaches, depending on both the scalp model and the data.
EEG Deblurring Techniques in a Clinical Context
Authors: Cincotti F. , Babiloni C. , Miniussi C. , Carducci F. , Moretti D. , Salinari S. , Pascual-Marqui R. , Rossini P. M. , Babiloni F.
Published: March 2018

Objectives:
EEG scalp potential distributions recorded in humans are affected by low spatial resolution and by the dependence on the electrical reference used. High resolution EEG technologies are available to drastically increase the spatial resolution of the raw EEG. Such technologies include the computation of surface Laplacian (SL) of the recorded potentials, as well as the use of realistic head models to estimate the cortical sources via linear inverse procedure (low resolution brain electromagnetic tomography, LORETA). However, these deblurring procedures are generally used in conjunction with EEG recordings with 64-128 scalp electrodes and with realistic head models obtained via sequential magnetic resonance images (MRIs) of the subjects. Such recording setup it is not often available in the clinical context, due to both the unavailability of these technologies and the scarce compliance of the patients with them. In this study we addressed the use of SL and LORETA deblurring techniques to analyze data from a standard 10-20 system (19 electrodes) in a group of Alzheimer disease (AD) patients.

Methods:
EEG data related to unilateral finger movements were gathered from 10 patients affected by AD. SL and LORETA techniques were applied for source estimation of EEG data. The use of MRIs for the construction of head models was avoided by using the quasi-realistic head model of the Brain Imaging Neurology Institute of Montreal.

Results:
A similar cortical activity estimated by the SL and LORETA techniques was observed during an identical time period of the acquired EEG data in the examined population.

Conclusions:
The results of the present study suggest that both SL and LORETA approaches can be usefully applied in the clinical context, by using quasi-realistic head modeling and a standard 10-20 system as electrode montage (19 electrodes). These results represent a reciprocal cross-validation of the two mathematically independent techniques in a clinical environment.
Hydrophobicity Analysis of Protein Primary Structures to Identify Helical Regions
Authors: Cerutti S. , Pattini L.
Published: March 2018

Objectives:
A wavelet based approach for the hydrophobicity analysis of protein primary structures is proposed to predict the presence of alpha helices in the secondary structure.

Methods:
The information about hydropathy profile periodicity content together with a score of probability of occurrence of a single amino acid allows the localization of alpha helices.

Results:
The accuracy is comparable to other consolidated predictors based on different techniques (i.e.: neural networks, hidden markov models).

Conclusion:
This method is particularly suitable to capture the amphiphilic character of the helical structures.
Live-Wires Using Path-Graphs
Authors: Hesser J. , König S.
Published: March 2018

Objectives:
This article discusses our new Path-Graph approach for the interactive Live-Wire segmentation method in 2D applied to pre-segmented data. Furthermore, we examine whether or not the Live-Lane extension provides advantages in combination with pre-segmentation.

Methods:
We automatically over-segment the image data in a preprocessing step, using region growing with an automatic seed point generation. The Live-Wire algorithm is applied on this mosaic data by using the outlines of the homogeneous regions as the basis for graph building. We present a new definition of this underlying graph where the edges of the standard graphs are turning into vertices and the vertices of the new graph are defined by the edge connectivity in the standard graph. For better differentiation we name our new graph Path-Graph and the original defined graph Node-Graph.

Results:
The quality evaluation is done by comparing our segmentation results with existing model data. We show that using the Path-Graph as basis for the Live-Wire algorithm instead of the Node-Graph allows for a finer segmentation. We achieve a reduction of incorrectly classified pixels by 20.66 per cent and a decrease of the mean boundary deviation by 11.61 per cent. Since savings on cost tree calculations are compensated by additional computation time required to compute the Live-Lanes, a performance loss of 2.41 per cent is measured.

Conclusions:
Our redefinition of the underlying graph increases the quality of the Live-Wire segmentation. The Live-Lane extension in combination with pre-segmentation is not justified for our data.
Establishing an International Reference Image Database for Research and Development in Medical Image Processing
Authors: Prinz M. , Schneider S. , Sipilä O. , Spinnler K. , Vallée J.-P. , Leeuw I. , Vogl R. , Wittenberg T. , Zahlmann G. , Horsch A.
Published: March 2018

Introduction:
The lack of comparability of evaluation results is one of the major obstacles of research and development in Medical Image Processing (MIP). The main reason for that is the usage of different image datasets with different quality, size and Gold standard.

Objectives:
Therefore, one of the goals of the Working Group on Medical Image Processing of the European Federation for Medical Informatics (EFMI WG MIP) is to develop first parts of a Reference Image Database.

Methods:
Kernel of the concept is to identify highly relevant medical problems with significant potential for improvement by MIP, and then to provide respective reference datasets. The EFMI WG MIP has primarily the role of a specifying group and an information broker, while the provider user relationships are defined by bilateral co-operation or license agreements.

Results:
An explorative database prototype has been implemented using the MySQL database software on the Web. Templates for provider user agreements have been worked out and already applied for own ‘pre-RID-MIP’ co-operations of the authors.

Discussion and Conclusion:
First steps towards a comprehensive reference image database have been done. Issues like funding, motivation, management, provision of Gold standards and evaluation guidelines are to be solved. Due to the interest from research groups and industry the efforts will be continued.
MRI-Based Individual 3D Region-of-Interest Atlases of the Human Brain
Authors: Kaiser H.-J. , Buell U. , Sabri O. , Wagenknecht G.
Published: March 2018

Objectives:
Introduction of a new atlas-based method for analyzing functional data which takes into account the variability of individual human brains and the partial volume effects of functional emission computed tomography images in complex anatomical 3D regions, as well as describing the underlying multi-modal image processing principles.

Methods:
3D atlas extraction is done directly by automated segmentation of individual magnetic resonance images of the patient’s head. This is done in two steps: voxel-based classification of T1-weighted images for tissue differentiation (low-level processing) is followed by knowledge-based analysis of the classified images for extraction of 3D anatomical regions (high-level processing). For atlas-based quantification of co-registered functional images, 3D anatomical regions can be convoluted with an idealized point spread function of the emission computed tomography system, after which a partial volume-dependent threshold can be determined.

Results:
Quantitative evaluation studies, based on 50 realistic software head phantoms and 24 image data sets obtained from healthy subjects and patients, show low misclassification rates and stable results for the neural network-based classification approach (mean ± SD 3.587 ± 0.466%, range 2.726-4.927%) as well as for the adjustable parameters of the knowledge-based approach. Computation time is <5 min for classification, <1 min for most of the extraction algorithms. The influence of the partial volume-dependent threshold is shown for an activation study.

Conclusions:
This new method allows 3D atlas generation without the need to warp individual image data to an anatomical or statistical brain atlas. Going beyond the purely tissue-oriented approach, partial volume effects of emission computed tomography images can be analyzed in complex anatomical 3D regions.
Influenza-associated Excess Mortality from Monthly Total Mortality Data for Germany from 1947 to 2000
Authors: Stilianakis N. I. , Uphoff H.
Published: March 2018

Objectives:
Death attributable to influenza is noted under various causes in the mortality statistics. Therefore, excess of total mortality is frequently used for the estimation of the entire impact of influenza on mortality. Various models for the estimation of the expected mortality are in use but are rather complex which hampers their routine use. A simple and hence transparent model was developed and applied to the total mortality in Germany from 1947 to 2000.

Methods:
The method is based on the pattern of the distribution of the mortality over the months. Additional trends over the time could be included with simple factors. In this manner the model was applicable over the total observation period.

Results:
The fit for the months where influenza was not epidemic was good and comparable to other models (R2 = 0.91). The estimated excess mortality is plausible and congruent with estimates based on other models.

Conclusion:
This method is applicable to long time series of any duration and obvious trends could be considered by simple factors in a readily identifiable and plausible way. Possible reductions in precision due to the consideration of a given monthly distribution pattern of the annual mortality seem tolerable with respect to the goodness of fit of the model. The estimation includes the pandemics of 1957/58 and 1968 to 1970.
Marfan Syndrome
Authors: Mátyás G. , Steinmann B. , Baumgartner D. , Baumgartner C.
Published: March 2018

Objectives:
Marfan syndrome (MFS) is an autosomal dominant inherited connective tissue disorder caused by mutations in the fibrillin-1 (FBN1) gene with variable clinical manifestations in the cardiovascular, musculoskeletal and ocular systems.

Methods:
Data of molecular genetic analysis and a catalogue of clinical manifestations including aortic elastic parameters were mined in order to (i) assess aortic abnormality before and during medical treatment, and to (ii) identify novel correlations between the genotype and phenotype of the disease using hierarchical cluster analysis and logistic regression analysis. A score measure describing the similarity between a patient’s clinical symptoms and a characteristic phenotype class was introduced.

Results:
A probabilistic model for monitoring the loss of aortic elasticity was built on merely aortic parameters of 34 patients with classic MFS and 43 control subjects showing a sensitivity of 82% and a specificity of 96%. The clinical phenotypes of 100 individuals with classical or suspected MFS were clustered yielding four different phenotypic expressions. The highest correlation was found between FBN1 missense mutations, which manifested as ectopia lentis, skeletal major and skin minor criteria, and two out of four clustered phenotypes. The probability of the presence of a missense mutation in both phenotype classes is approximately 70%.

Conclusions:
Monitoring of aortic elastic properties during medical treatment may serve as additional criterion to indicate elective surgical interventions. Genotype-phenotype correlation may contribute to anticipate the clinical consequences of specific FBN1 mutations more comprehensively and may be helpful to identify MFS patients at risk at an early stage of disease.
Integration of Genomic Data in Electronic Health Records
Authors: Schmidt S. , Sax U.
Published: March 2018

Objectives:
In this paper we give an overview about the challenge the postgenomic era poses on biomedical informaticists. The occurrence of new (genomic) data types necessitates new data models, new viewing metaphors and methods to deal with the disclosure of genomic data. We discuss integration issues when inferring phenotype and genotype data. Another challenge is to find the right phenotype to genotype data in order to get appropriate case numbers for sound clinical genotype-phenotype inference studies.

Methods:
Genomic data could be integrated in an Electronic Health Record (EHR) in several ways. We describe patient-centered and pointer-based integration strategies and the corresponding data types and data models. The inference mechanisms for the interpretation of raw data contain different agents. We describe vertical, horizontal and temporal agents.

Results:
We have to deal with several new data types, not being standardized for EHR integration. Genomic data tends to be more structured than phenotype data. Beyond the development of new data models, vertical, horizontal and temporal agents have to be developed in order to link genotype and phenotype. As the genomic EHR will contain very sensitive data, confidentiality and privacy concerns have to be addressed.

Conclusions:
Given the necessity to capture both environment and genomic state of a patient and their interaction, clinical information systems have to be redesigned. While genotyping seems to be automatable easily, this is not the case for clinical information. More integration work on terminologies and ontologies has to be done.
Why a System Awarded as “MIE ’99 Best Paper” Failed to Be Used and Hence to Affect Patient’s Health?
Authors: Mazzoleni M. C.
Published: March 2018

Objective:
The failure of a promising system is described with the aim of identifying the errors and the unfavourable conditions that led to such a result.

Methods:
The system, based on the AHCPR guideline for pressure ulcers prevention and integrated into the already existing clinical information system, is aimed at supporting nurse’s activities for: the risk assessment of the inpatient at the beginning of the hospitalization; the prevention plan, customized to each specific patient; the work plan for each day for all the patients; the report of the non-compliances to the GL and of the workload of the nurses.

Results:
The system was abandoned after a short period. The reported reasons for the abandonment were: too strict constraints in the work-plan and the mandatory updating of the tasks at the end of each shift (both executed and not); the double writing activity, on paper first and afterward on the workstation.

The first complaint was almost unrecoverable and not related to the system from the implementation point of view. Portable notebooks and wireless connections to the LAN could have been a solution for the second problem. Simultaneously a portable device at the bed side could have benefited many other features of the clinical information system. We proposed to quantify the added value, if any, due to making the information system available as close as possible to the points on the wards where information are both generated and used. The proposal was rejected.

Conclusions:
In our experience in a hospital setting, closing the gap among the medical informatics minority, the health professionals and the hospital management, through their collaborative responsibilities and participation in the decision-making process, can make the difference between the success and the failure of a good computer-based solution.
Advanced EHR Architectures–Promises or Reality
Authors: Blobel B. G. M. E.
Published: March 2018

Objectives:
Forming the informational reflection of the patients and their care, the Electronic Health Record (EHR) is the core application of any complex health information system or health network. Such an ideally lifelong history file must be reliable, flexible, adaptable to new concepts and technologies, and robust, to allow for sharing knowledge over its lifetime. A sophisticated architecture must be chosen for meeting this challenge.

Methods:
An advanced EHR architecture for designing and implementing future-proof EHR systems must be a model of generic properties required for any Electronic Patient Record to provide communicable, comprehensive, useful, effective, and legally binding records that preserve their integrity over the time, independent of platforms and systems as well as of national special-ties. The resulting approach is based on the ISO Reference Model – Open Distributed Processing.

Results:
Based on advanced architectural principles introduced in the paper, a new generation of EHR systems has been designed and implemented for demonstrating the feasibility of the approach. This result is presented and evaluated regarding the achievements and problems using the component-based paradigm of model-driven health information system architectures.

Conclusions:
The future-proof EHR approach that has been established has been shortly evaluated. Advantages regarding flexibility, reliability, and portability of policy-driven, highly secure, role-dependent applications have to be considered in the light of performance as well as of the availability of network and application services.
The Gießen Tumor Documentation System (GTDS) – Review and Perspectives
Authors: Dudeck J. , Altmann U.
Published: March 2018

Objectives:
GTDS is a documentation system used by more than 40 German hospital cancer registries. This paper discusses the factors that contributed to its success concerning design, development, and routine use.

Methods:
Success is measured in terms of the system‘s financial independence of public grants and its successful use by the registries. Success factors are presented in a descriptive way covering the topics of development (tools and development team) as well as system‘s functionality and user support. The description of the system’s use and user satisfaction was collected in a user survey conducted in 1999.

Results:
GTDS has become the main tool in hospital cancer registries in Germany and remarkably contributed to their success. A comprehensive data network between hospital cancer registries and population-based cancer registries has especially been established in the new states. After the first years of routine use the registries produce valuable data analyses on the basis of common tools. Under specific conditions physicians use the system directly for treatment management. The system succeeded to be financed by support contracts for continuous development which indicates generally good user acceptance. Close interaction between users and developers is important to meet user requirements during development and maintenance.

Conclusion:
Important success factors are the strong ministry‘s support including initial sponsoring and introduction of support contracts, the comprehensive functionality as well as flexibility and broad user support which allow the adaptation to different environments.
Semantic Interoperability
Authors: Engel K. , Pharowe P. , Blobel B. G. M. E.
Published: March 2018

Objectives:
To meet the challenge for high quality and efficient care, highly specialized and distributed healthcare establishments have to communicate and co-operate in a semantically interoperable way. Information and communication technology must be open, flexible, scalable, knowledge-based and service-oriented as well as secure and safe.

Methods:
For enabling semantic interoperability, a unified process for defining and implementing the architecture, i.e. structure and functions of the cooperating systems’ components, as well as the approach for knowledge representation, i.e. the used information and its interpretation, algorithms, etc. have to be defined in a harmonized way. Deploying the Generic Component Model, systems and their components, underlying concepts and applied constraints must be formally modeled, strictly separating platform-independent from platform-specific models.

Results:
As HL7 Version 3 claims to represent the most successful standard for semantic interoperability, HL7 has been analyzed regarding the requirements for model-driven, service-oriented design of semantic interoperable information systems, thereby moving from a communication to an architecture paradigm. The approach is compared with advanced architectural approaches for information systems such as OMG’s CORBA 3 or EHR systems such as GEHR/openEHR and CEN EN 13606 Electronic Health Record Communication.

Conclusion:
HL7 Version 3 is maturing towards an architectural approach for semantic interoperability. Despite current differences, there is a close collaboration between the teams involved guaranteeing a convergence between competing approaches.
The Semantics of Procedures and Diseases in SNOMED® CT
Authors: Hanser S. , Hahn U. , Rogers J. , Schulz S.
Published: March 2018

Objectives:
SNOMED® CT is emerging as a reference terminology for the entire health care process. It claims to be founded on logic-based modelling principles. In this article, we analyze a special encoding scheme for diseases and procedures in SNOMED® CT, the so-called relationship groups (RGs), which had been devised to avoid ambiguities in definitions.

Methods:
We reformulate SNOMED® CT’s relationship groups in the format of description logics in order to check whether RGs serve the needs they were designed for.

Results:
We show that a considerable proportion of relationship groups represent hidden mereological relations. We also report discrepancies encountered between the defined semantics of many SNOMED® CT terms and their intuitive meaning, as well as inconsistencies detected between the definition of various complex composed terms and the definition of their top-level parents.

Conclusions:
We formulate recommendations for improving SNOMED® CT by replacing most occurrences of relation groups by formally more adequate “part-of” relations.
A Simple Method to Estimate Tobacco-related Lung Cancer Deaths Based on Smoking Prevalence Data
Authors: Winkler V. , Gbangou A. , Kouyate B. , Becher H.
Published: March 2018

Objective:
Tobacco is the major cause of cancer and a relevant risk factor for several other chronic diseases. Due to the epidemiological transition in developing countries with overall increasing life expectancy there is an increasing relevance of chronic diseases to the total burden of diseases. Furthermore, there are indications for a rise in the consumption of tobacco products in developing countries. Since in Africa data on smoking prevalence are scarce and cancer diagnosis is often imprecise or missing, it is difficult to estimate the current and future number of cancer cases attributable to tobacco smoking. In this paper, we present an approach to estimate the effects of smoking on lung cancer in selected developing countries in Africa.

Methods:
We combined data on smoking prevalence from different African countries with estimates on age-specific lung cancer rates in smokers and non-smokers from industrialized countries and data on age and sex distribution in African countries. We perform a sensitivity analysis to evaluate the effect of the assumptions necessary for the procedure.

Results:
If the smoking prevalence in African countries will remain on the current level, we estimate age-specific lung cancer rates lower than those in Germany. Despite the relatively small proportion of adults aged 50 and more which is the age when most cancer cases occur, there is an appreciable number of deaths from lung cancer that could be prevented when smoking prevalence could be reduced. Depending on assumptions we estimate up about 50,000 lung cancer deaths per year in Africa, most of which could be prevented.

Conclusions:
Efforts for smoking prevalence reduction are much more needed in the developing world. Better and more comprehensive data on smoking are needed for more precise estimates.
Are KISS Data Representative of German Intensive Care Units?
Authors: Schoop R. , Beyersmann J. , Schumacher M. , Zuschneid I. , Rücker G.
Published: March 2018

Objectives:
Data collected within the German nosocomial infection surveillance system KISS are recommended as reference data for judging nosocomial infection rates in German intensive care units (ICUs). It is unknown whether the KISS data tend to under- or overestimate the true infection incidence rates. In this article, methodological aspects of the SIR1 study on the incidence of nosocomial infections are discussed, with the aim of estimating unbiased incidence rates of nosocomial infections in interdisciplinary German ICUs and examining whether the KISS data are representative.

Methods:
We discuss the following methodological issues: 1) Sample size estimation. 2) Stratified random sampling of German ICUs. 3) Investigation of seasonal effects. 4) Statistical modeling of incidence rates using a negative binomial regression model. 5) Comparison of weighted incidence rates with the standardized rate ratio (SRR).

Results:
Random sampling proved difficult to realize in practice since many ICUs refused to participate, particularly those in small hospitals. Analysis was adjusted for hospital size. No seasonal trends were found in the KISS data. Due to marked differences between ICUs, the number of infections is over-dispersed compared to a Poisson model, so negative binomial regression was used. Fifty ICUs were observed for two consecutive months each, corresponding to 21,832 patient days, during which 262 infections occurred. Infections were more frequent in large hospitals. The incidence rates provided by the SIR study are on average (SRR) 1.89 (1.63-2.20) times as large as those estimated by the KISS system.

Conclusion:
For estimating nosocomial infection incidence rates, random sampling and statistical modeling of over-dispersion were successfully performed. The study provides evidence that the KISS surveillance system tends to underestimate the true incidence rates of nosocomial infections in German ICUs.
Independence Estimating Equations for Controlled Clinical Trials with Small Sample Sizes
Authors: Dahmen G. , Ziegler A.
Published: March 2018

Objectives:
The application of independence estimating equations (IEE) for controlled clinical trials (CCTs) has recently been discussed, and recommendations for its use have been derived for testing hypotheses. The robust estimator of variance has been shown to be liberal for small sample sizes. Therefore a series of modifications has been proposed. In this paper we systematically compare confidence intervals (CIs) proposed in the literature for situations that are common in CCTs.

Methods:
Using Monte-Carlo simulation studies, we compared the coverage probabilities of CIs and non-convergence probabilities for the parameters of the mean structure for small samples using modifications of the variance estimator proposed by Mancl and de Rouen [7], Morel et al. [8] and Pan [3].

Results:
None of the proposed modifications behave well in each investigated situation. For parallel group designs with repeated measurements and binary response the method proposed by Pan maintains the nominal level. We observed non-convergence of the IEE algorithm in up to 10% of the replicates depending on response probabilities in the treatment groups. For comparing slopes with continuous responses, the approach of Morel et al. can be recommended.

Conclusions:
Results of non-convergence probabilities show that IEE should not be used in parallel group designs with binary endpoints and response probabilities close to 0 or 1. Modifications of the robust variance estimator should be used for sample sizes up to 100 clusters for CI estimation.
Professional Ethics for System Developers in Health Care
Authors: Timpka T.
Published: March 2018

Medical informaticians are multidisciplinary professionals responsible for developing complex technical systems. The aim of this study was to investigate how a code of ethics can help medical informaticians in avoiding design failures. An exploratory case study was performed to identify factors related to failure during system development. The literature on professional ethics was reviewed to derive a preliminary code of ethics. The case study showed that collaboration across individual and professional values is required to avoid failure during system development in health care. Having either the employer or the health care providers in focus for moral judgments may be misleading and cause confusion. The preliminary code emphasizes socialization, education and cooperation rather than enforced compliance. As a code is a distillation of experiences, its major benefit to medical informaticians should be its clarification of the profession’s position in society.
Analysis and Design of an Ontology for Intensive Care Diagnoses
Authors: Abu-Hanna A. , Cornet R. , Zwetsloot-Schonk J. H. M. , Stoutenbeek C. P. , de Keizer N. F.
Published: March 2018

Information about the patient‘s health status and about medical problems in general, play an important role in stratifying a patient population for quality assurance of intensive care. A terminological system which supports both the description of health problems for daily care practice and the aggregation of diagnostic information for evaluative research, is desirable for description of the patient population. This study describes the engineering of an ontology that facilitates a terminological system for intensive care diagnoses. We analyzed the criteria for such an ontology and evaluated existing terminological systems according to these criteria. The analysis shows that none of the existing terminological systems completely satisfies all our criteria. We describe choices regarding design, content and representation of a new ontology on which an adequate terminological system is based. The proposed ontology is characterized by the explicit and formal representation of the domain model, the metaspecification of its concepts, the vocabulary to define concepts and the nomenclature to support the composition of new concepts.