Refine
Year of publication
Document Type
- Article (18)
- Conference Proceeding (4)
- Preprint (3)
- Doctoral Thesis (1)
- Working Paper (1)
Has Fulltext
- yes (27)
Is part of the Bibliography
- no (27)
Keywords
- Aerosol (1)
- Aktienanalyse (1)
- Aktienbewertung (1)
- Atherosclerosis (1)
- Brain tumors (1)
- Börsenkurs (1)
- Cancer (1)
- Cardiovascular diseases (1)
- Children and adolescents (1)
- Decision making (1)
Institute
- Medizin (11)
- Physik (9)
- Geowissenschaften (6)
- Frankfurt Institute for Advanced Studies (FIAS) (3)
- Informatik (3)
- Wirtschaftswissenschaften (1)
Background: There is absence of specific biomarkers and an incomplete understanding of the pathophysiology of exudative age-related macular degeneration (AMD).
Methods and findings: Eighty-eight vitreous samples (73 from patients with treatment naïve AMD and 15 control samples from patients with idiopathic floaters) were analyzed with capillary electrophoresis coupled to mass spectrometry in this retrospective case series to define potential candidate protein markers of AMD. Nineteen proteins were found to be upregulated in vitreous of AMD patients. Most of the proteins were plasma derived and involved in biological (ion) transport, acute phase inflammatory reaction, and blood coagulation. A number of proteins have not been previously associated to AMD including alpha-1-antitrypsin, fibrinogen alpha chain and prostaglandin H2-D isomerase. Alpha-1-antitrypsin was validated in vitreous of an independent set of AMD patients using Western blot analysis. Further systems biology analysis of the data indicated that the observed proteomic changes may reflect upregulation of immune response and complement activity.
Conclusions: Proteome analysis of vitreous samples from patients with AMD, which underwent an intravitreal combination therapy including a core vitrectomy, steroids and bevacizumab, revealed apparent AMD-specific proteomic changes. The identified AMD-associated proteins provide some insight into the pathophysiological changes associated with AMD.
Aims: Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk.
Methods and results: From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies.
In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95–1.02) in group A, 0.98 (0.93–1.04) in group B, and 0.95 (0.89–1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07–1.23) in group A, 1.13 (1.05–1.22) in group B, and 1.12 (1.05–1.20) in group C.
Conclusions: We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals.
Aim: Pharmacoresistance is a major burden in epilepsy treatment. We aimed to identify genetic biomarkers in response to specific antiepileptic drugs (AEDs) in genetic generalized epilepsies (GGE). Materials & methods: We conducted a genome-wide association study (GWAS) of 3.3 million autosomal SNPs in 893 European subjects with GGE – responsive or nonresponsive to lamotrigine, levetiracetam and valproic acid. Results: Our GWAS of AED response revealed suggestive evidence for association at 29 genomic loci (p <10-5) but no significant association reflecting its limited power. The suggestive associations highlight candidate genes that are implicated in epileptogenesis and neurodevelopment. Conclusion: This first GWAS of AED response in GGE provides a comprehensive reference of SNP associations for hypothesis-driven candidate gene analyses in upcoming pharmacogenetic studies.
Influence of the sFlt-1/PlGF ratio on clinical decision-making in women with suspected preeclampsia
(2016)
Objective: To evaluate the influence of the soluble fms-like tyrosine kinase 1/placental growth factor ratio in physicians’ decision making in pregnant women with signs and symptoms of preeclampsia in routine clinical practice.
Methods: A multicenter, prospective, open, non-interventional study enrolled pregnant women presenting with preeclampsia signs and symptoms in several European perinatal care centers. Before the soluble fms-like tyrosine kinase 1/placental growth factor ratio result was known, physicians documented intended clinical procedures using an iPad® application (data locked/time stamped). After the result was available, clinical decisions were confirmed or revised and documented. An independent adjudication committee evaluated the appropriateness of decisions based on maternal/fetal outcomes. Clinician decision making with regard to hospitalization was the primary outcome.
Results: In 16.9% of mothers (20/118) the hospitalization decision was changed after knowledge of the ratio. In 13 women (11.0%), the initial decision to hospitalize was changed to no hospitalization. In seven women (5.9%) the revised decision was hospitalization. All revised decisions were considered appropriate by the panel of adjudicators (McNemar test; p < 0.0001).
Conclusions: The use of the soluble fms-like tyrosine kinase 1/placental growth factor test influenced clinical decision making towards appropriate hospitalization in a considerable proportion of women with suspected preeclampsia. This is the first study to demonstrate the impact of angiogenic biomarkers on decision making in a routine clinical practice.
Background: Microdeletions are known to confer risk to epilepsy, particularly at genomic rearrangement ‘hotspot’ loci. However, microdeletion burden not overlapping these regions or within different epilepsy subtypes has not been ascertained.
Objective: To decipher the role of microdeletions outside hotspots loci and risk assessment by epilepsy subtype.
Methods: We assessed the burden, frequency and genomic content of rare, large microdeletions found in a previously published cohort of 1366 patients with genetic generalised epilepsy (GGE) in addition to two sets of additional unpublished genome-wide microdeletions found in 281 patients with rolandic epilepsy (RE) and 807 patients with adult focal epilepsy (AFE), totalling 2454 cases. Microdeletions were assessed in a combined and subtype-specific approaches against 6746 controls.
Results: When hotspots are considered, we detected an enrichment of microdeletions in the combined epilepsy analysis (adjusted p=1.06×10−6,OR 1.89, 95% CI 1.51 to 2.35). Epilepsy subtype-specific analyses showed that hotspot microdeletions in the GGE subgroup contribute most of the overall signal (adjusted p=9.79×10−12, OR 7.45, 95% CI 4.20–13.5). Outside hotspots , microdeletions were enriched in the GGE cohort for neurodevelopmental genes (adjusted p=9.13×10−3,OR 2.85, 95% CI 1.62–4.94). No additional signal was observed for RE and AFE. Still, gene-content analysis identified known (NRXN1, RBFOX1 and PCDH7) and novel (LOC102723362) candidate genes across epilepsy subtypes that were not deleted in controls.
Conclusions: Our results show a heterogeneous effect of recurrent and non-recurrent microdeletions as part of the genetic architecture of GGE and a minor contribution in the aetiology of RE and AFE.
Background Microdeletions are known to confer risk to epilepsy, particularly at genomic rearrangement “hotspot” loci. However, deciphering their role outside hotspots and risk assessment by epilepsy sub-type has not been conducted.
Methods We assessed the burden, frequency and genomic content of rare, large microdeletions found in a previously published cohort of 1,366 patients with Genetic Generalized Epilepsy (GGE) plus two sets of additional unpublished genome-wide microdeletions found in 281 Rolandic Epilepsy (RE) and 807 Adult Focal Epilepsy (AFE) patients, totaling 2,454 cases. These microdeletion sets were assessed in a combined analysis and in sub-type specific approaches against 6,746 ethnically matched controls.
Results When hotspots are considered, we detected an enrichment of microdeletions in the combined epilepsy analysis (adjusted-P= 2.00×10-7; OR = 1.89; 95%-CI: 1.51-2.35), where the implicated microdeletions overlapped with rarely deleted genes and those involved in neurodevelopmental processes. Sub-type specific analyses showed that hotspot deletions in the GGE subgroup contribute most of the signal (adjusted-P = 1.22×10-12; OR = 7.45; 95%-CI = 4.20-11.97). Outside hotspot loci, microdeletions were enriched in the GGE cohort for neurodevelopmental genes (adjusted-P = 4.78×10-3; OR = 2.30; 95%-CI = 1.42-3.70), whereas no additional signal was observed for RE and AFE. Still, gene content analysis was able to identify known (NRXN1, RBFOX1 and PCDH7) and novel (LOC102723362) candidate genes affected in more than one epilepsy sub-type but not in controls.
Conclusions Our results show a heterogeneous effect of recurrent and non-recurrent microdeletions as part of the genetic architecture of GGE and a minor to negligible contribution in the etiology of RE and AFE.
The MYRRHA Project (Multi Purpose Hybrid Reactor for High Tech Applications) at Mol/belgium will be a user facility with emphasis on research with neutron generated by a spallation source. One main aspect is the demonstration of nuclear waste technology using an accelerator driven system. A superconducting linac delivers a 4 mA, 600 MeV proton beam. The first accelerating section is covered by the 17 MeV injector. It consists of a proton source, an RFQ, two room temperature CH cavities and 4 superconducting CH-cavities. The initial design has used an RF frequency of 352 MHz. Recently the frequency of the injector has been set to 176 MHz. The main reason is the possible use of a 4-rod-RFQ with reduced power dissipation and energy, respectively. The status of the overall injector layout including cavity design is presented.
As the successor of the EUROTRANS project, the MAX project is aiming to continue the R&D effects for a European Accelerator-Driven System and to bring the conceptual design to reality. The layout of the driver linac for MAX will follow the reference design made for the XT-ADS phase of the EUROTRANS project. For the injector part, new design strategies and approaches, e.g. half resonant frequency, half transition-energy between the RFQ and the CH-DTL, and using the 4-rod RFQ structure instead of the originally proposed 4-vane RFQ, have been conceived and studied to reach a more reliable CW operation at reduced costs. In this paper, the design and simulation results of the MAX injector are presented.
In this study, we develop a technique for estimating a firm’s expected cost of equity capital derived from analyst consensus forecasts and stock prices. Building on the work of Gebhardt/Lee/-Swaminathan (2001) and Easton/Taylor/Shroff/Sougiannis (2002), our approach allows daily estimation, using only publicly available information at that date. We then estimate the expected cost of equity capital at the market, industry and individual firm level using historical German data from 1989-2002 and examine firm characteristics which are systematically related to these estimates. Finally, we demonstrate the applicability of the concept in a contemporary case study for DaimlerChrysler and the European automobile industry.
The crossbar-H-mode (CH) structure is the first superconducting multicell drift tube cavity for the low and medium energy range operated in the H21 mode. Because of the large energy gain per cavity, which leads to high real estate gradients, it is an excellent candidate for the efficient acceleration in high power proton and ion accelerators with fixed velocity profile. A prototype cavity has been developed and tested successfully with a gradient of 7MV/m. A few new superconducting CH cavities with improved geometries for different high power applications are under development at present. One cavity (f=325 MHz, β=0.16, seven cells) is currently under construction and studied with respect to a possible upgrade option for the GSI UNILAC. Another cavity (f=217 MHz, β=0.059, 15 cells) is designed for a cw operated energy variable heavy ion linac application. Furthermore, the EUROTRANS project (European research program for the transmutation of high level nuclear waste in an accelerator driven system, 600 MeV protons, 352 MHz) is one of many possible applications for this kind of superconducting rf cavity. In this context a layout of the 17 MeV EUROTRANS injector containing four superconducting CH cavities was proposed by the Institute for Applied Physics (IAP) Frankfurt. The status of the cavity development related to the EUROTRANS injector is presented.
MYRRHA is conceived as an accelerator driven system (ADS) for transmutation of high level nuclear waste. The neutron source is created by coupling a proton accelerator of 600 MeV with a 4 mA proton beam, a spallation source and a sub-critical core. The IAP of Frankfurt University is responsible for the development of the 17 MeV injector operated at 176 MHz. The injector consists of a 1.5 MeV 4-Rod-RFQ and six CH-drifttube-structures. The first two CH-structures will be operated at room temperature and the other CH-structures are superconducting cavities assembled in one cryo-module. To achieve the extremely high reliability required by the ADS application, the design of the 17 MeV injector has been intensively studied, with respect to thermal issues, minimum peak fields and field distribution.
Genetic generalised epilepsy (GGE) is the most common form of genetic epilepsy, accounting for 20% of all epilepsies. Genomic copy number variations (CNVs) constitute important genetic risk factors of common GGE syndromes. In our present genome-wide burden analysis, large (≥ 400 kb) and rare (< 1%) autosomal microdeletions with high calling confidence (≥ 200 markers) were assessed by the Affymetrix SNP 6.0 array in European case-control cohorts of 1,366 GGE patients and 5,234 ancestry-matched controls. We aimed to: 1) assess the microdeletion burden in common GGE syndromes, 2) estimate the relative contribution of recurrent microdeletions at genomic rearrangement hotspots and non-recurrent microdeletions, and 3) identify potential candidate genes for GGE. We found a significant excess of microdeletions in 7.3% of GGE patients compared to 4.0% in controls (P = 1.8 x 10-7; OR = 1.9). Recurrent microdeletions at seven known genomic hotspots accounted for 36.9% of all microdeletions identified in the GGE cohort and showed a 7.5-fold increased burden (P = 2.6 x 10-17) relative to controls. Microdeletions affecting either a gene previously implicated in neurodevelopmental disorders (P = 8.0 x 10-18, OR = 4.6) or an evolutionarily conserved brain-expressed gene related to autism spectrum disorder (P = 1.3 x 10-12, OR = 4.1) were significantly enriched in the GGE patients. Microdeletions found only in GGE patients harboured a high proportion of genes previously associated with epilepsy and neuropsychiatric disorders (NRXN1, RBFOX1, PCDH7, KCNA2, EPM2A, RORB, PLCB1). Our results demonstrate that the significantly increased burden of large and rare microdeletions in GGE patients is largely confined to recurrent hotspot microdeletions and microdeletions affecting neurodevelopmental genes, suggesting a strong impact of fundamental neurodevelopmental processes in the pathogenesis of common GGE syndromes.
Explosive volcanism affects weather and climate. Primary volcanic ash particles which act as ice nuclei (IN) can modify the phase and properties of cold tropospheric clouds. During the Eyjafjallajökull volcanic eruption we have measured the highest ice nucleus number concentrations (>600 L) in our record of 2 years of daily IN measurements in central Germany. Even in Israel, located about 5000 km away from Iceland, IN were as high as otherwise only during desert dust storms. These measurements are the only ones available on the properties of IN in the Eyjafjallajökull plume. The measured high concentrations and high activation temperature (−8 °C) point to an important impact of volcanic ash on microphysical and radiative properties of clouds through enhanced glaciation.
We have sampled atmospheric ice nuclei (IN) and aerosol in Germany and in Israel during spring 2010. IN were analyzed by the static vapor diffusion chamber FRIDGE, as well as by electron microscopy. During the Eyjafjallajökull volcanic eruption of April 2010 we have measured the highest ice nucleus number concentrations (>600 l−1) in our record of 2 yr of daily IN measurements in central Germany. Even in Israel, located about 5000 km away from Iceland, IN were as high as otherwise only during desert dust storms. The fraction of aerosol activated as ice nuclei at −18 °C and 119% rhice and the corresponding area density of ice-active sites per aerosol surface were considerably higher than what we observed during an intense outbreak of Saharan dust over Europe in May 2008.
Pure volcanic ash accounts for at least 53–68% of the 239 individual ice nucleating particles that we collected in aerosol samples from the event and analyzed by electron microscopy. Volcanic ash samples that had been collected close to the eruption site were aerosolized in the laboratory and measured by FRIDGE. Our analysis confirms the relatively poor ice nucleating efficiency (at −18 °C and 119% ice-saturation) of such "fresh" volcanic ash, as it had recently been found by other workers. We find that both the fraction of the aerosol that is active as ice nuclei as well as the density of ice-active sites on the aerosol surface are three orders of magnitude larger in the samples collected from ambient air during the volcanic peaks than in the aerosolized samples from the ash collected close to the eruption site. From this we conclude that the ice-nucleating properties of volcanic ash may be altered substantially by aging and processing during long-range transport in the atmosphere, and that global volcanism deserves further attention as a potential source of atmospheric ice nuclei.
In order to quantitatively analyse the chemical and dynamical evolution of the polar vortex it has proven extremely useful to work with coordinate systems that follow the vortex flow. We propose here a two-dimensional quasi-Lagrangian coordinate system {X i, delta X i}, based on the mixing ratio of a long-lived stratospheric trace gas i, and its systematic use with i = N2O, in order to describe the structure of a well-developed Antarctic polar vortex. In the coordinate system {X i, delta X i} the mixing ratio X i is the vertical coordinate and delta X i = X i(theta) - X i vort(theta) is the meridional coordinate (X i vort(theta) being a vertical reference profile in the vortex core). The quasi-Lagrangian coordinates {X i, delta X i} persist for much longer time than standard isentropic coordinates, potential temperature theta and equivalent latitude Phi e, do not require explicit reference to geographic space, and can be derived directly from high-resolution in situ measurements. They are therefore well-suited for studying the evolution of the Antarctic polar vortex throughout the polar winter with respect to the relevant chemical and microphysical processes. By using the introduced coordinate system {X N2O, delta X N2O} we analyze the well-developed Antarctic vortex investigated during the APE-GAIA (Airborne Polar Experiment – Geophysica Aircraft in Antarctica – 1999) campaign (Carli et al., 2000). A criterion, which uses the local in-situ measurements of X i=X i(theta) and attributes the inner vortex edge to a rapid change (delta-step) in the meridional profile of the mixing ratio X i, is developed to determine the (Antarctic) inner vortex edge. In turn, we suggest that the outer vortex edge of a well-developed Antarctic vortex can be attributed to the position of a local minimum of the X H2O gradient in the polar vortex area. For a well-developed Antarctic vortex, the delta X N2O-parametrization of tracer-tracer relationships allows to distinguish the tracer inter-relationships in the vortex core, vortex boundary region and surf zone and to examine their meridional variation throughout these regions. This is illustrated by analyzing the tracer-tracer relationships X i : X N2O obtained from the in-situ data of the APE-GAIA campaign for i = CFC-11, CFC-12, H-1211 and SF6. A number of solitary anomalous points in the CFC-11 : N2O correlation, observed in the Antarctic vortex core, are interpreted in terms of small-scale cross-isentropic dispersion.