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1.
J Neural Transm (Vienna) ; 122(9): 1323-8, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25757983

ABSTRACT

The pathogenesis of executive dysfunction in geriatric depression remains uncertain although causal bidirectional relationships with depression have been discussed. Previous studies have described a potential link with 'vascular depression'. In this study, we investigate the influence of vascular risk factors and magnetic resonance imaging markers of structural brain ageing, such as increasing deep white matter hyperintensities (DWMH), on executive function in an age-homogeneous population-based study cohort. A total of 606 participants of identical age (75.8 years; standard deviation 0.45 years) took part in the baseline investigation of the Vienna Transdanube Ageing (VITA) study. Each participant underwent a full psychometric examination with standardised neuroimaging and clinical chemistry investigations. Participants were re-examined with the same protocol after exactly 30 and 60 months. Data refer to the individuals who completed the examination at baseline. In the ordinal logistic regression, fewer years of education (P < 0.0001), Trail Making Test-A (P < 0.0001), high homocysteine (P = 0.001), and depression (P < 0.0001) were significantly associated with Trail Making Test-B (TMT-B) values. A significant influence of other vascular risk factors, such as lipids, diabetes, and smoking, on executive dysfunction was not observed. A comparison of both lacunes and DWMH with respect to the TMT-B results showed no significant correlation. Our data do not support the notion that vascular pathogenesis might underlie executive dysfunction.


Subject(s)
Executive Function , Vascular Diseases/epidemiology , Vascular Diseases/psychology , Aged , Area Under Curve , Austria/epidemiology , Brain/pathology , Cohort Studies , Female , Humans , Logistic Models , Male , Neuropsychological Tests , Psychometrics , Risk Factors , Vascular Diseases/pathology , White Matter/pathology
2.
J Nutr Health Aging ; 16(8): 687-94, 2012 Aug.
Article in English | MEDLINE | ID: mdl-23076510

ABSTRACT

OBJECTIVE: Increased serum homocysteine and low folate levels are associated with a higher rate of conversion to dementia. This study examined the influence of vitamin B12/folic acid intake on the conversion from mild cognitive impairment (MCI) to dementia. PARTICIPANTS: A community dwelling cohort of older adults (N=81) from the Vienna Transdanube aging study with MCI. DESIGN: Prospective study with a retrospective evaluation of vitamin intake. MEASUREMENTS: Laboratory measurements, brain magnetic resonance imaging, and cognitive functioning were assessed at baseline and at five-year follow-up. RESULTS: The self-reported combined use of folic acid and vitamin B12 for more than one year was associated with a lower conversion rate to dementia. Serum levels of homocysteine and vitamin B12 as measured at baseline or at five years were not associated with conversion. Higher folate levels at baseline in females predicted a lower conversion rate to dementia. The assessment of brain morphological parameters by magnetic resonance imaging revealed higher serum folate at baseline, predicting lower medial temporal lobe atrophy and higher levels of homocysteine at baseline, predicting moderate/severe global brain atrophy at five years. Users of vitamin B12 or folate, independent of time and pattern of use, had lower grades of periventricular hyperintensities and lower grades of deep white matter lesions as compared to non-users. CONCLUSIONS: These results from a middle European study support observations on the protective ability of folate in MCI patients with respect to conversion to dementia; they also point to a participation of homocysteine metabolism on processes associated with brain atrophy.


Subject(s)
Aging , Cognitive Dysfunction/diet therapy , Dementia/prevention & control , Dietary Supplements , Disease Progression , Folic Acid/therapeutic use , Vitamin B 12/therapeutic use , Aged , Atrophy , Austria , Brain/growth & development , Brain/pathology , Cognitive Dysfunction/blood , Cognitive Dysfunction/complications , Cognitive Dysfunction/physiopathology , Cohort Studies , Dementia/etiology , Female , Folic Acid/administration & dosage , Folic Acid/blood , Follow-Up Studies , Humans , Hyperhomocysteinemia/blood , Hyperhomocysteinemia/complications , Hyperhomocysteinemia/diet therapy , Hyperhomocysteinemia/physiopathology , Longitudinal Studies , Male , Prospective Studies , Retrospective Studies , Vitamin B 12/administration & dosage , Vitamin B 12/blood
3.
J Neural Transm (Vienna) ; 117(11): 1247-52, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20809068

ABSTRACT

Globally, cardiovascular diseases (CVDs) are the number one cause of all mortalities. Of these deaths, 7.6 million are due to heart attacks, and 5.7 millions are due to stroke. The Vienna Transdanube Aging Study (VITA), a population-based cohort study, enabled us to evaluate associations between the known major risk factors for cerebrovascular and CVDs and their appearance beyond age 75 years. Using a single birth cohort, age was excluded as confounding factor. In the baseline investigations in the Danube Hospital, 606 individuals took part and were examined completely at baseline. After 60 months, 508 patients were re-examined. Each participant underwent an indepth investigation with the duration of 7 h, including neuropsychological testing, as well as analyses of biochemical, clinical chemical and genetic parameters, and magnetic resonance imaging (MRI) of the brain. In the present study, only a history of cerebral and cardiovascular events at the baseline or smoking was associated significantly with the appearance of CVDs. In a multiple model both risk factors-history of cerebral and cardiovascular events at the baseline (p = 0.0003, OR 2.36, 95% CI 1.49-3.76) and smoking (p = 0.0005, OR 1.57, 95% CI 1.22-2.03)-remained significant. However, the predictive value of this assessment model was low. The rescaled r² of the model was 0.088. A significant correlation was found only between exposure to cigarette smoke or a history of previous CVDs, such as stroke or myocardial infarction. Smoking or earlier CVDs greatly increase the risk for further cerebral and cardiovascular events in persons after 75 years.


Subject(s)
Cerebrovascular Disorders/etiology , Aged , Aged, 80 and over , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cerebrovascular Disorders/epidemiology , Cohort Studies , Female , Humans , Male , Risk Factors , Smoking/adverse effects
4.
Eur Radiol ; 19(6): 1519-28, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19184034

ABSTRACT

Accuracy of MRI reports is taken for granted. In this paper the inter-observer reliability in the interpretation of meniscal lesions, degree of chondropathy, and integrity of the ACL was analyzed while taking the radiologist's experience and field strength into account. Fifty-two MRI studies of knees were interpreted by 11 radiologists independently. Twenty-two were acquired on 1.0-T, 20 on 1.5-T, and 10 on 3.0-T systems. Four of the radiologists had more than 5 years and seven had 3 to 5 years of experience in interpreting MRI studies. The findings were compared with the intra-operative findings. Inter-observer variance, specificity, and sensitivity were evaluated for each field strength. Inter-observer correlation ranged between 0.370 for cartilage lesions and 0.597 for meniscal tears. Correlation values did not increase with experience or field strength. The number of false reports was dependent on the observer, but not on field strength. The rate of false interpretations was significantly higher for most criteria in the less experienced group. In conclusion, inter-observer correlation was low, although the diagnostic criteria were defined. The use of the classification scheme should be standardized by uniform training. Radiologist experience seems to be more important than field strength.


Subject(s)
Anterior Cruciate Ligament Injuries , Anterior Cruciate Ligament/pathology , Image Enhancement/methods , Knee Injuries/diagnosis , Magnetic Resonance Imaging/methods , Menisci, Tibial/pathology , Tibial Meniscus Injuries , Adolescent , Adult , Female , Humans , Male , Middle Aged , Observer Variation , Reproducibility of Results , Sensitivity and Specificity , Young Adult
6.
Zentralbl Neurochir ; 69(4): 182-6, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18949683

ABSTRACT

BACKGROUND: The incidence of clinically silent meningiomas in 75-year-old individuals was determined five years ago in the Vienna Transdanube Ageing Study (VITA). At the time a watch-and-wait approach was recommended in cases of incidentally discovered meningiomas. METHODS: 420 out of the initial cohort of 532 test persons underwent control investigations after 2.5 and 5 years. Six of the nine known tumors were measured again and the patients underwent clinical, neurological and psychological tests. Changes in tumor size were determined and all new tumors seen on MRI investigation were carefully reviewed. RESULTS: Tumor growth was minimal in all six cases that were followed over the entire period. Two of the original meningioma patients had died and one patient had undergone tumor resection. CONCLUSIONS: The watch-and-wait approach recommended after the VITA study was confirmed by the present investigation. Tumor growth was slow in all cases; no clinical symptoms have been registered thus far. The intervals between control investigations may even be prolonged depending on the location of the tumor. In this age group the operation appears to pose a greater risk than the presence of an asymptomatic tumor.


Subject(s)
Aged, 80 and over/physiology , Meningioma/pathology , Cohort Studies , Contrast Media , Disease Progression , Follow-Up Studies , Gadolinium , Humans , Insulin-Like Growth Factor I/metabolism , Magnetic Resonance Imaging , Meningioma/surgery , Neurosurgical Procedures
8.
J Neural Transm Suppl ; (72): 181-8, 2007.
Article in English | MEDLINE | ID: mdl-17982893

ABSTRACT

The etiology of white matter hyperintensities (WMH) seen on T2-weighted cranial magnetic resonance images is a matter of debate. We investigated deep and periventricular WMH in the brains of a community-based cohort of 532 subjects aged 75-76 years. The objective of this study was to determine whether WMH at age of 75 years were associated rather with vascular factors than with degenerative factors. Arterial hypertension treated with antihypertensive drugs favored WMH, and WMH were found more frequently in subjects with focal vascular lesions. Additionally, we found significant associations between both, deep white matter and periventricular hyperintensities, and focal atrophy of medial temporal lobe structures. The odds ratio for deep WMH in subjects with more severe medial temporal atrophy was 4.4 (95%-CI: 1.9-9.8) that for periventricular hyperintensities was 3.9 (95%-CI: 1.7-8.8). These findings might indicate that not only vascular factors alone but also degenerative factors favor the occurrence of WMH after the age of 75 years.


Subject(s)
Alzheimer Disease/pathology , Brain/pathology , Dementia, Vascular/pathology , Magnetic Resonance Imaging , Nerve Fibers, Myelinated/pathology , Neurodegenerative Diseases/pathology , Age Factors , Aged , Atrophy , Austria , Cerebral Ventricles/pathology , Cohort Studies , Dementia, Multi-Infarct/pathology , Female , Hippocampus/pathology , Humans , Hypertensive Encephalopathy/pathology , Male , Risk Factors , Temporal Lobe/pathology
10.
Neurology ; 68(4): 288-91, 2007 Jan 23.
Article in English | MEDLINE | ID: mdl-17242334

ABSTRACT

OBJECTIVE: To compare the rates of conversion to Alzheimer dementia (AD) between subtypes of mild cognitive impairment (MCI) in a community-based birth cohort investigated at age 75 and followed up after 30 months. METHODS: The Vienna Trans-Danube Aging Study investigated every inhabitant of the area on the left shore of the river Danube who was born between May 1925 and June 1926. With use of the official voting registry, 1505 subjects were contacted and 697 participated. Data refer to the cohort of 581 nondemented individuals who completed extensive neuropsychological examination at baseline. Follow-up after 30 months was possible in 476 probands (35 deceased). RESULTS: The 141 patients with MCI at baseline were classified into two subtypes. At follow-up, 41 of these patients with MCI were diagnosed with AD. Conversion rates to AD were 48.7% (CI: 32.4 to 65.2) for amnestic MCI and 26.8% (CI: 17.6 to 37.8) for nonamnestic MCI. Another 49 AD cases originated from cognitive health at baseline (12.6%; CI: 9.4 to 16.3). CONCLUSIONS: Patients with mild cognitive impairment (MCI) showed a high probability to be diagnosed with Alzheimer dementia (AD) after 30 months. Subtypes of MCI were not useful in defining early stages of various types of dementia: Not only amnestic MCI but also nonamnestic MCI converted frequently to AD, and conversion to vascular dementia and dementia with Lewy bodies was not restricted to nonamnestic MCI.


Subject(s)
Alzheimer Disease/epidemiology , Alzheimer Disease/etiology , Cognition Disorders/complications , Cognition Disorders/epidemiology , Aged , Aged, 80 and over , Alzheimer Disease/psychology , Cognition Disorders/classification , Cognition Disorders/psychology , Cohort Studies , Disease Progression , Female , Follow-Up Studies , Humans , Male , Residence Characteristics , Risk Factors
11.
Am J Geriatr Psychiatry ; 14(6): 531-7, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16731722

ABSTRACT

OBJECTIVE: Cerebrovascular lesions that are apparent in magnetic resonance scans and regioselective atrophy of the brain have been proposed as a causative or exacerbating factor in depression with late-life onset. The objective of this study was to investigate whether deep white matter or periventricular hyperintensities, small ischemic lesions, and brain atrophy contribute to late-onset depression in the nondemented elderly. METHOD: Based on a group of 606 individuals of identical age (75.8 years, standard deviation: 0.45 years) residing in two districts of Vienna, the authors built a case-control cohort (ratio: 1:4) consisting of 51 individuals with late-onset major or minor depression matched with 204 subjects of identical gender and education status without depression, resulting in two groups that were homogenous with respect to age, place of residence, gender, and education. Scores for focal brain lesions, mediotemporal lobe atrophy, and ventricular enlargement as well as risk factors for vascular disease were compared with cognition and depression status. RESULTS: Depressed individuals had significantly lower scores than nondepressed subjects in all measures of cognitive and executive function. No significant relation was found between a diagnosis of depression and any type of discrete brain lesions, but measures of brain atrophy (Cella Media indices, mediotemporal atrophy) showed a clear statistical relation to depression. No relationship was found between depression and lipid parameters. CONCLUSION: The authors found no indication that white matter hyperintensities or minor ischemic lesions played a role in our depressed cohort, casting doubt on the vascular hypothesis of late-onset depression.


Subject(s)
Brain Ischemia/epidemiology , Brain/pathology , Depressive Disorder, Major/epidemiology , Population Surveillance/methods , Aged , Atrophy/pathology , Brain Ischemia/diagnosis , Case-Control Studies , Cohort Studies , Female , Follow-Up Studies , Humans , Magnetic Resonance Imaging , Male , Residence Characteristics , Risk Factors
13.
Rofo ; 174(12): 1511-5, 2002 Dec.
Article in German | MEDLINE | ID: mdl-12471522

ABSTRACT

PURPOSE: Spinal meningeal Gd-DTPA enhancement after cranial surgery is a known observation of a not well understood underlying mechanism. This paper demonstrates that this MRI finding is a normal meningeal reaction to subarachnoid hemorrhage, which should not be mistaken for metastatic spread. MATERIAL AND METHODS: Three pediatric patients were examined by MRI for metastatic spread of malignant infratentorial tumors along the spinal canal two to nine days after the removal of the primary cerebral lesion. The findings were compared with a control group that underwent cranial surgery (cyst resection or fenestration of the posterior cranial fossa) without major bleeding into the subarachnoid space. Unenhanced and enhanced sequences were obtained to prove that the high signal within the CSF is caused by an abnormal Gd-DTPA uptake and not by methemoglobin. RESULTS: Meningeal enhancement was observed in all patients with intraoperative bleeding resembling subarachnoid masses on enhanced T 1 -weighted images. This was not present in any patient of the control group. This finding lasts for approximately two weeks. CONCLUSION: The meningeal enhancement renders immediate postoperative studies inconclusive for the detection of metastatic spread. Consequently, the obligatory tumor staging along the spinal canal should ideally be done prior to the resection of a cerebral tumor.


Subject(s)
Astrocytoma/diagnosis , Astrocytoma/surgery , Blood Loss, Surgical , Brain Neoplasms/diagnosis , Brain Neoplasms/surgery , Brain Stem , Cerebellar Neoplasms/diagnosis , Cerebellar Neoplasms/surgery , Magnetic Resonance Imaging/methods , Medulloblastoma/diagnosis , Medulloblastoma/surgery , Meninges , Subarachnoid Hemorrhage/diagnosis , Child , Child, Preschool , Contrast Media , Cranial Fossa, Posterior , Diagnosis, Differential , Female , Follow-Up Studies , Gadolinium DTPA , Humans , Infant , Lumbosacral Region , Male , Neoplasm Metastasis/diagnosis , Neoplasm Staging , Postoperative Period , Time Factors
14.
J Neural Transm Suppl ; (62): 105-16, 2002.
Article in English | MEDLINE | ID: mdl-12456056

ABSTRACT

The Vienna Transdanube Aging study "VITA" is a prospective, interdisciplinary cohort-study of all 75-years old inhabitants of the 21. and 22. district of Vienna (n = 1,745), which started in May 2000. The study design is described in this paper for the first time. The main scientific question of the study concerns the prediction of incident dementia in the elderly. The main statistical analysis will compare 8 predictors: episodic memory, verbal fluency, subjective memory complaints, depression, APOE-epsilon4, MAO-B activity in thrombocytes, MRT hippocampal atrophy, and MRT atrophy of the substantia innominata. The whole investigation comprises medical and psychosocial interviews, psychological tests, psychiatric and neurological scales, blood characteristic, genetic factors and cranial magnetic resonance imaging. Various variables will be compared with each other concerning sensitivity and specificity of prediction of cognitive decline. The dependent variable of the intended statistical analysis will be the individual's difference between Mini Mental State Examination scores at the two times of investigation. A high level of participation in geriatric epidemiological studies increases the general applicability of results but recruitment procedures must not ignore the individual's right to privacy and integrity. Using a liberal recruitment procedure as recommended by the local ethics commission the level of participation is between 36.7% and 44.3%.


Subject(s)
Aging , Alzheimer Disease/epidemiology , Cognition Disorders/epidemiology , Aged , Female , Humans , Male , Patient Dropouts/psychology , Patient Selection , Prospective Studies , Socioeconomic Factors
15.
Skeletal Radiol ; 30(2): 72-6, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11310202

ABSTRACT

OBJECTIVE: To evaluate the findings in MRI-studies of the knee in recreational long-distance runners after competition and to assess the reversibility of the findings. DESIGN AND PATIENTS: Eight recreational long-distance runners underwent MRI studies of the knee before, immediately after and 6-8 weeks after taking part in the Vienna City Marathon. The studies were evaluated regarding alterations of pre-existing lesions and new pathological findings. RESULTS: In six runners without major pre-existing alterations no negative effects were experienced. In one runner with pre-existing grade III alterations of the menisci, signs of progressive osteoarthritis were experienced 2 months after the competition. In all other cases increased meniscal signal alterations and minor signal changes in the bone marrow after the race were transitory. CONCLUSION: In healthy individuals no negative long-term-effects were experienced. Pre-existing high-grade lesions of the menisci might be a predisposing risk for osteoarthritis, triggered by the stress of long-distance running.


Subject(s)
Knee Joint/pathology , Magnetic Resonance Imaging , Running , Adult , Bone Marrow/pathology , Cartilage, Articular/pathology , Edema/pathology , Humans , Ligaments, Articular/pathology , Male , Menisci, Tibial/pathology , Middle Aged , Prospective Studies , Synovial Fluid , Tendons/pathology
16.
Ultraschall Med ; 18(1): 35-8, 1997 Feb.
Article in German | MEDLINE | ID: mdl-9173526

ABSTRACT

AIM: To evaluate sonography as a tool for initial diagnosis in emergency room patients with abdominal trauma. METHOD: 174 cases of abdominal trauma were selected from 1837 emergency care patients. The initial sonographic findings were compared to CT-evaluation, operative and autopsy results, and both clinical and sonographic follow-up. RESULTS: In 31 cases initial sonographic findings were positive, leading to 6 laparotomies. In another 6 cases, changes of follow-up sonographic testing led to laparotomy. In 143 patients, the initial sonographic evaluation was negative. In this group, follow-up evaluation revealed changes in 16 cases leading to 3 laparotomies. In 8 patients with stab injuries, the negative sonographic study was confirmed by operative findings. CONCLUSION: Sonography is a well-tested diagnostic method in evaluating patients with abdominal trauma. Follow-up examinations-even with negative initial results-are needed. While the time interval between evaluations depends on the individual risk factors, hourly reevaluation is generally appropriate.


Subject(s)
Abdominal Injuries/diagnostic imaging , Emergencies , Shock/diagnostic imaging , Abdominal Injuries/pathology , Abdominal Injuries/surgery , Emergency Service, Hospital , Humans , Laparoscopy , Multiple Trauma/diagnostic imaging , Multiple Trauma/pathology , Multiple Trauma/surgery , Sensitivity and Specificity , Shock/pathology , Shock/surgery , Ultrasonography , Wounds, Nonpenetrating/diagnostic imaging , Wounds, Nonpenetrating/pathology , Wounds, Nonpenetrating/surgery , Wounds, Penetrating/diagnostic imaging , Wounds, Penetrating/pathology , Wounds, Penetrating/surgery
17.
Invest Radiol ; 30(3): 186-91, 1995 Mar.
Article in English | MEDLINE | ID: mdl-7797418

ABSTRACT

RATIONALE AND OBJECTIVES: In this experimental study, the authors examined whether laser printed hardcopies from digital storage phosphor radiographs yield diagnostic performance equal to conventional film-screen radiographs in the detection of simulated miliary disease, using a standardized object. METHODS: A commercially available anthropomorphic chest phantom was used for radiographic evaluation. Miliary disease was simulated by superimposing one to four sheets of millet seeds on the lungs, resembling a miliary disease pattern with varying degrees of detectability. An observer study (receiver-operating characteristic) with eight radiologists was conducted to compare the reader performance using hardcopies of computed storage phosphor radiography versus the conventional film-screen system, optimized for chest x-rays. The digitally generated images were presented as a double-image hardcopy, with a conventionally adopted version and an edge enhanced image version. RESULTS: When analyzed separately, one out of the eight observers performed slightly better using the conventional films. When treated as a group, analysis of the areas under the receiver-operating characteristic curves demonstrated no significant difference in reader performance for each of the systems under investigation (t = 0.286). The Wilcoxon test could not prove a statistical difference. CONCLUSION: Storage phosphor technology is a method that yields equal diagnostic performance as conventional film in evaluating miliary disease of the chest.


Subject(s)
Lung Diseases/diagnostic imaging , Lung/diagnostic imaging , Models, Structural , Radiographic Image Enhancement/methods , X-Ray Intensifying Screens , Adult , Animals , Humans , Male , ROC Curve , Radiographic Image Enhancement/instrumentation , X-Ray Intensifying Screens/statistics & numerical data
18.
Invest Radiol ; 29(8): 773-6, 1994 Aug.
Article in English | MEDLINE | ID: mdl-7960628

ABSTRACT

OBJECTIVES: The authors' experiences concerning the use of video-framegrabbers for the integration of ultrasound devices into a fully digital imaging environment are presented. METHODS: Video acquisition workstations (VAW) (Siemens, Gammasonics Inc., Hoffman Estates, IL) are used in our department to link ultrasound devices to the picture archiving and communication system (PACS). A study was carried out concerning the impact of this integration on throughput by comparing the average times for image acquisition and storage in this digital system with the times found in a conventional archive, which is still used for some ultrasound units. The annual costs for the two kinds of archives were compared. RESULTS AND CONCLUSION: Video acquisition is a feasible way of integrating ultrasound in a digital environment. No impact on throughput has been found for the radiologist carrying out the examination, but for the assisting technologist, the times for image retrieval and archiving could be reduced from 3 minutes and 8 seconds to 24 seconds per patient. The instant availability of previous studies could be increased from 93.5% to almost 100%. Archive costs could be reduced by 28%, with further reductions to be expected using different archive configurations.


Subject(s)
Optical Storage Devices , Radiology Department, Hospital/organization & administration , Radiology Information Systems , Ultrasonography , Austria , Humans , Radiographic Image Enhancement , Systems Integration , Time Factors
19.
Radiologe ; 34(6): 291-9, 1994 Jun.
Article in German | MEDLINE | ID: mdl-8090867

ABSTRACT

We present our experience during the first 21 months of using hospital-wide network technology and digital archiving in connection with digital radiology in the Radiology Department at the SMZO/Danube hospital in Vienna. This means digital generation, archiving and distribution of radiographs as well as monitor reporting embedded in HIS and RIS. The clinical use of PACS demands full integration of all subsystems and modalities in a digital way, as was first realized at the Danube Hospital. With this approach, a reduction in radiation dose, improved communication and thus a reduction in the length of hospital stay and health care cost are attained.


Subject(s)
Hospital Information Systems , Radiographic Image Enhancement/instrumentation , Radiology Information Systems/instrumentation , Austria , Computer Communication Networks/instrumentation , Computer Systems , Humans
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