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1004 Publications visible to you, out of a total of 1004
Prevalence of BRCA1/2 germline mutations in 21 401 families with breast and ovarian cancer.
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

PURPOSE: To characterise the prevalence of pathogenic germline mutations in BRCA1 and BRCA2 in families with breast cancer (BC) and ovarian cancer (OC) history. PATIENTS AND METHODS: Data from 21 401 … families were gathered between 1996 and 2014 in a clinical setting in the German Consortium for Hereditary Breast and Ovarian Cancer, comprising full pedigrees with cancer status of all individual members at the time of first counselling, and BRCA1/2 mutation status of the index patient. RESULTS: The overall BRCA1/2 mutation prevalence was 24.0% (95% CI 23.4% to 24.6%). Highest mutation frequencies were observed in families with at least two OCs (41.9%, 95% CI 36.1% to 48.0%) and families with at least one breast and one OC (41.6%, 95% CI 40.3% to 43.0%), followed by male BC with at least one female BC or OC (35.8%; 95% CI 32.2% to 39.6%). In families with a single case of early BC (<36 years), mutations were found in 13.7% (95% CI 11.9% to 15.7%). Postmenopausal unilateral or bilateral BC did not increase the probability of mutation detection. Occurrence of premenopausal BC and OC in the same woman led to higher mutation frequencies compared with the occurrence of these two cancers in different individuals (49.0%; 95% CI 41.0% to 57.0% vs 31.5%; 95% CI 28.0% to 35.2%). CONCLUSIONS: Our data provide guidance for healthcare professionals and decision-makers to identify individuals who should undergo genetic testing for hereditary breast and ovarian cancer. Moreover, it supports informed decision-making of counselees on the uptake of genetic testing.

Authors: K. Kast, K. Rhiem, B. Wappenschmidt, E. Hahnen, J. Hauke, B. Bluemcke, V. Zarghooni, N. Herold, N. Ditsch, M. Kiechle, M. Braun, C. Fischer, N. Dikow, S. Schott, N. Rahner, D. Niederacher, T. Fehm, A. Gehrig, C. Mueller-Reible, N. Arnold, N. Maass, G. Borck, N. de Gregorio, C. Scholz, B. Auber, R. Varon-Manteeva, D. Speiser, J. Horvath, N. Lichey, P. Wimberger, S. Stark, U. Faust, B. H. Weber, G. Emons, S. Zachariae, A. Meindl, R. K. Schmutzler, C. Engel

Date Published: 2nd Mar 2016

Publication Type: Journal article

Human Diseases: breast cancer, ovarian cancer

Compression of dementia morbidity by higher education
LIFE - Leipzig Research Center for Civilization Diseases

Abstract (Expand)

Objectives: The concept of compression of morbidity suggests that compressing cognitive morbidity into a shorter lifetime period would result in a better cumulative lifetime cognitive functioning. Some … lifestyle factors, like higher education, that are known to protect cognitive functioning in old age and lower dementia risk, could compress cognitive morbidity. Therefore the aim of our study was to investigate whether higher education leads to a better cumulative lifetime cognitive functioning and, hence, the compression of cognitive morbidity. Methods: Data were derived from the population-based Leipzig longitudinal study of the aged (LEILA75+). From 1998-2005, individuals aged 75 years and older underwent up to seven assessments at a 1.5-year interval and a long-term follow-up assessment after 15 years (2013). Analyses on the impact of higher education on compression of cognitive morbidity were carried out via multilevel logistic mixed-models and tobit analyses using the participants’ age as time scale (n=742). Results: The results revealed that more years of education were significantly associated with a better cognitive functioning but not with the age at dementia onset or the age at death. Computation of cumulative lifetime cognitive functioning was weighted for survival probability and indicated a gain of 21 MMSE points during the lifetime period 75 through 100 years of age by having more than 12 years of education compared to having less than 9 years of education. Conclusion: Overall, the findings suggest a compression of cognitive morbidity by higher education prior to dementia onset. More years of education could therefore contribute to a better cognitive functioning even under consideration of survival probability. Hence, efforts to ensure access to higher education for as many people in a population as possible might compress disease burden due to cognitive morbidity.

Authors: F. S. Then, T. Luck, H. Matschinger, M. C. Angermeyer, S. G. Riedel-Heller

Date Published: 1st Mar 2016

Publication Type: Not specified

Human Diseases: dementia

Improved prediction of complex diseases by common genetic markers: state of the art and further perspectives
Genetical Statistics and Systems Biology

Abstract (Expand)

Reliable risk assessment of frequent, but treatable diseases and disorders has considerable clinical and socio-economic relevance. However, as these conditions usually originate from a complex interplay … between genetic and environmental factors, precise prediction remains a considerable challenge. The current progress in genotyping technology has resulted in a substantial increase of knowledge regarding the genetic basis of such diseases and disorders. Consequently, common genetic risk variants are increasingly being included in epidemiological models to improve risk prediction. This work reviews recent high-quality publications targeting the prediction of common complex diseases. To be included in this review, articles had to report both, numerical measures of prediction performance based on traditional (non-genetic) risk factors, as well as measures of prediction performance when adding common genetic variants to the model. Systematic PubMed-based search finally identified 55 eligible studies. These studies were compared with respect to the chosen approach and methodology as well as results and clinical impact. Phenotypes analysed included tumours, diabetes mellitus, and cardiovascular diseases. All studies applied one or more statistical measures reporting on calibration, discrimination, or reclassification to quantify the benefit of including SNPs, but differed substantially regarding the methodological details that were reported. Several examples for improved risk assessments by considering disease-related SNPs were identified. Although the add-on benefit of including SNP genotyping data was mostly moderate, the strategy can be of clinical relevance and may, when being paralleled by an even deeper understanding of disease-related genetics, further explain the development of enhanced predictive and diagnostic strategies for complex diseases.

Authors: Bent Müller, Arndt Wilcke, Anne-Laure Boulesteix, Jens Brauer, Eberhard Passarge, Johannes Boltze, Holger Kirsten

Date Published: 1st Mar 2016

Publication Type: Journal article

Validating new diagnostic imaging criteria for primary progressive aphasia via anatomical likelihood estimation meta-analyses.
LIFE Adult

Abstract (Expand)

Recently, diagnostic clinical and imaging criteria for primary progressive aphasia (PPA) have been revised by an international consortium (Gorno-Tempini et al. Neurology 2011;76:1006-14). The aim of … this study was to validate the specificity of the new imaging criteria and investigate whether different imaging modalities [magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET)] require different diagnostic subtype-specific imaging criteria. Anatomical likelihood estimation meta-analyses were conducted for PPA subtypes across a large cohort of 396 patients: firstly, across MRI studies for each of the three PPA subtypes followed by conjunction and subtraction analyses to investigate the specificity, and, secondly, by comparing results across MRI vs. FDG-PET studies in semantic dementia and progressive nonfluent aphasia. Semantic dementia showed atrophy in temporal, fusiform, parahippocampal gyri, hippocampus, and amygdala, progressive nonfluent aphasia in left putamen, insula, middle/superior temporal, precentral, and frontal gyri, logopenic progressive aphasia in middle/superior temporal, supramarginal, and dorsal posterior cingulate gyri. Results of the disease-specific meta-analyses across MRI studies were disjunct. Similarly, atrophic and hypometabolic brain networks were regionally dissociated in both semantic dementia and progressive nonfluent aphasia. In conclusion, meta-analyses support the specificity of new diagnostic imaging criteria for PPA and suggest that they should be specified for each imaging modality separately.

Authors: S. Bisenius, J. Neumann, M. L. Schroeter

Date Published: 23rd Feb 2016

Publication Type: Not specified

Human Diseases: aphasia

Evaluation eines Mikromanipulators für die Mittelohrchirurgie: Eine präklinische Studie
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND Microsurgical preparation is limited by geometric and mechanical constraints. In preparation for clinical use, this study investigates performance, ease of handling and precision of a novel …l manipulator concept for microsurgery. MATERIAL AND METHODS A group of 15 ENT experienced doctors, as well as a group of 17 medical students with low/non surgical experience participated in the study. Each of the subjects carried out 4 trials of simulated surgeries on a phantom with built-in force sensors. The task was to apply a defined force between 1.5 and 2 N using a Fisch micro perforator, 16 cm length, 0.4 mm (Storz) targeting holes with a diameter of 0.5 mm. For comparison, the Fisch micro perforator was moved manually or with the manipulator. RESULTS Assessing the total number of errors proved a significantly lower error number (p\textless0.0001) and an improvement of the accuracy of 76% with the manipulator. The time requirement for the procedure with the micro manipulator is on average 2-3 times higher than with manual control (p\textless0.0001). But it is notable that this time requirement significantly decreases with training (p\textless0.0001). CONCLUSION The study shows a significant reduction in the number of errors by using a new manipulator concept compared to the non-augmented human hand in an experimental setup. We observed a significant learning effect when subjects applied the micro manipulator, resulting in reduction of the time requirement while maintaining a constant number of errors.

Authors: A. Peschka, Th Berger, Th Maier, M. Scholz, T. C. Lüth, G. Strauß

Date Published: 9th Feb 2016

Publication Type: Journal article

Serum BDNF correlates with connectivity in the (pre)motor hub in the aging human brain--a resting-state fMRI pilot study.
LIFE Adult

Abstract (Expand)

Brain-derived neurotrophic factor (BDNF) has been discussed to be involved in plasticity processes in the human brain, in particular during aging. Recently, aging and its (neurodegenerative) diseases … have increasingly been conceptualized as disconnection syndromes. Here, connectivity changes in neural networks (the connectome) are suggested to be the most relevant and characteristic features for such processes or diseases. To further elucidate the impact of aging on neural networks, we investigated the interaction between plasticity processes, brain connectivity, and healthy aging by measuring levels of serum BDNF and resting-state fMRI data in 25 young (mean age 24.8 +/- 2.7 (SD) years) and 23 old healthy participants (mean age, 68.6 +/- 4.1 years). To identify neural hubs most essentially related to serum BDNF, we applied graph theory approaches, namely the new data-driven and parameter-free approach eigenvector centrality (EC) mapping. The analysis revealed a positive correlation between serum BDNF and EC in the premotor and motor cortex in older participants in contrast to young volunteers, where we did not detect any association. This positive relationship between serum BDNF and EC appears to be specific for older adults. Our results might indicate that the amount of physical activity and learning capacities, leading to higher BDNF levels, increases brain connectivity in (pre)motor areas in healthy aging in agreement with rodent animal studies. Pilot results have to be replicated in a larger sample including behavioral data to disentangle the cause for the relationship between BDNF levels and connectivity.

Authors: K. Mueller, K. Arelin, H. E. Moller, J. Sacher, J. Kratzsch, T. Luck, S. Riedel-Heller, A. Villringer, M. L. Schroeter

Date Published: 2nd Feb 2016

Publication Type: Not specified

High acceptance of an early dyslexia screening test involving genetic analyses in Germany
Genetical Statistics and Systems Biology

Abstract (Expand)

Dyslexia is a developmental disorder characterized by severe problems in the acquisition of reading and writing skills. It has a strong neurobiological basis. Genetic influence is estimated at 50-70%. … One of the central problems with dyslexia is its late diagnosis, normally not before the end of the 2nd grade, resulting in the loss of several years for early therapy. Currently, research is focusing on the development of early tests for dyslexia, which may be based on EEG and genetics. Our aim was to determine the acceptance of such a future test among parents. We conducted a representative survey in Germany with 1000 parents of children aged 3-7 years, with and without experience of dyslexia. 88.7% of the parents supported the introduction of an early test for dyslexia based on EEG and genetics; 82.8% would have their own children tested, and 57.9% were willing to pay for the test if health insurance did not cover the costs. Test acceptance was significantly higher if parents had prior experience with dyslexia. The perceived benefits of such a test were early recognition and remediation and, preventing deficits. Concerns regarded the precision of the test, its potentially stigmatizing effect and its costs. The high overall support for the test leads to the conclusion that parents would accept a test for dyslexia based on EEG and genetics.

Authors: Arndt Wilcke, Bent Müller, Gesa Schaadt, Holger Kirsten, Johannes Boltze

Date Published: 1st Feb 2016

Publication Type: Journal article

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