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Reactive Skin Decontamination Lotion (RSDL®) is used for the decontamination of Chemical Warfare Agents and Toxic Industrial Compounds after dermal exposure. It has to be stockpiled over a long period and is handled in all climatic zones. Therefore stability is an essential matter of concern. In this work we describe a study to the chemical stability of RSDL® as basis for an estimation of shelf life. We analysed RSDL® for the active ingredient 2,3-butandione monoxime (diacetylmonooxime, DAM), the putative degradation product dimethylglyoxime (DMG) and unknown degradation products by means of a reversed phase high pressure liquid chromatography (HPLC). Calculations were done according to the Arrhenius equation. Based on the temperature dependent rate constants, the time span was calculated, until defined threshold values for DAM and DMG subject to specification and valid regulations were exceeded. The calculated data were compared to the ones gathered from stockpiled samples and samples exposed during foreign mission. The decline of DAM followed first order kinetics, while formation of DMG could be described by zero order kinetics. The rate constants were distinctively temperature dependent. Calculated data were in good accordance to the measured ones from stockpile and mission. Based on a specified acceptable DAM-content of 90% and a valid threshold value of 0.1% (w/w) for the degradation product DMG, RSDL® proved to be stable for at least four years if stored at the recommended conditions of 15°C-30°C. If continuously stored at higher temperatures shelf life will decrease markedly. Therefore RSDL® is an object for risk orientated quality monitoring during storage.

Bosch–Boonstra–Schaaf optic atrophy syndrome (BBSOAS) is a recently described autosomal dominant disorder caused by mutations in the NR2F1 gene. There are presently 28 cases of BBSOAS described in the literature. Its common features include developmental delay, intellectual disability, hypotonia, optic nerve atrophy, attention deficit disorder, autism spectrum disorder, seizures, hearing defects, spasticity, and thinning of the corpus callosum. Here we report two unrelated probands with novel, de novo, missense variants in NR2F1. The first is a 14-yr-old male patient with hypotonia, intellectual disability, optic nerve hypoplasia, delayed bone age, short stature, and altered neurotransmitter levels on cerebrospinal fluid testing. The second is a 5-yr-old female with severe developmental delay, motor and speech delay, and repetitive motion behavior. Whole-exome sequencing identified a novel missense NR2F1 variant in each case, Cys86Phe in the DNA-binding domain in Case 1, and a Leu372Pro in the ligand-binding domain in Case 2. The presence of clinical findings compatible with BBSOAS along with structural analysis at atomic resolution using homology-based molecular modeling and molecular dynamic simulations, support the pathogenicity of these variants for BBSOAS. Short stature, abnormal CNS neurotransmitters, and macrocephaly have not been previously reported for this syndrome and may represent a phenotypic expansion of BBSOAS. A review of published cases along with new evidence from this report support genotype–phenotype correlations for this disorder.

Pathogenic variants in EBF3 were recently described in three back-to-back publications in association with a novel neurodevelopmental disorder characterized by intellectual disability, speech delay, ataxia, and facial dysmorphisms. In this report, we describe an additional patient carrying a de novo missense variant in EBF3 (c.487C>T, p.(Arg163Trp)) that falls within a conserved residue in the zinc knuckle motif of the DNA binding domain. Without a solved structure of the DNA binding domain, we generated a homology-based atomic model and performed molecular dynamics simulations for EBF3, which predicted decreased DNA affinity for p.(Arg163Trp) compared with wild-type protein and control variants. These data are in agreement with previous experimental studies of EBF1 showing the paralogous residue is essential for DNA binding. The conservation and experimental evidence existing for EBF1 and in silico modeling and dynamics simulations to validate comparable behavior of multiple variants in EBF3 demonstrates strong support for the pathogenicity of p.(Arg163Trp). We show that our patient presents with phenotypes consistent with previously reported patients harboring EBF3 variants and expands the phenotypic spectrum of this newly identified disorder with the additional feature of a bicornuate uterus.

A new copolymer based on hydrophobically modified polyacrylamide was characterized by its rheological behavior. Viscosities were measured at various temperatures and salinities in comparison to a regular acrylamide/sodium acrylate copolymer (HPAM). It is proven that the viscosity of this new associative polymers increases with temperature, while the viscosity of HPAM is decreasing. This effect was further explored in porous media studies. Polymer solution was injected into a Bentheimer sandstone with a permeability of around 2 Darcy at 20°C and the pressure drop was measured along the core. From the pressure drop the resistance factor, RF, was derived, which is a measure of the in-situ viscosity in the porous medium. Next, the temperature was increased to 45°C. This resulted in an increase of the RF from 15 to 94. At 60°C a RF of even 152 was observed. By reducing the flow rate from 0.5 ml/min to 0.1 ml/min the RF could be further increased to 562. Finally the flow rate and the temperature were set to the initial values and a RF of 21 was measured, which shows that the thermothickening behavior of the novel polymer is reversible. Monitoring the effluent viscosity indicated that the increase of the RF / in-situ viscosity is due to polymer being retained in the porous media. This retained polymer lowers the permeability of the rock pores and thereby increases RF. By lowering the temperature the properties are switched back to the original state and the polymer is released from the rock matrix. The thermothickening behavior of the discussed copolymer can be quite beneficial for polymer flooding applications. During injection at surface temperature the viscosity of the fluid is low and therefore it can be injected at high rates. Once the polymer solution migrates deeper into the reservoir formation, the temperature of the fluid will rise gradually; in-situ viscosity will increase and simultaneously the flow rate will decrease. Both effects will help to improve sweep efficiency. In general, the magnitude of the RF can be adjusted by modifying the polymer structure and hence the copolymer can be optimized for specific field conditions.

Background Since 2005 an interdisciplinary German apheresis working group has been established by members of both German Societies of Nephrology and of Lipidologists and completed the data set for the registry according to the current guidelines and the German indication guideline for apheresis in 2009. In 2011 the German Lipoprotein Apheresis Registry (GLAR) was launched and data are available over nearly 5 years now. Methods and results During the time period 2012–2016, 71 German apheresis centers collected retrospective and prospective observational data of 1435 patients undergoing lipoprotein apheresis (LA) treatment of high LDL-C levels and/or high Lp (a) levels suffering from cardiovascular disease (CVD) or progressive CVD. A total of 15,527 completely documented LA treatments were entered into the database. All patients treated by LA showed a median LDL-C reduction rate of 67.5%, and a median Lp (a) reduction rate of 71.1%. Analog to the Pro(a)LiFe pattern, patient data were analyzed to the incidence rate of coronary events (MACE) 1 and 2 years before the beginning of LA treatment (y-2 and y‑1) and prospectively two years on LA treatment (y + 1 and y + 2). During two years of LA treatment a MACE reduction of 78% was observed. In the years considered, side effects of LA treatment were low (5.9%) and mainly comprised puncture problems. Conclusions The data generated by the GLAR shows that LA lowers the incidence rate of cardiovascular events in patients with high LDL-C and/or high Lp (a) levels, progressive CVD, and maximally tolerated lipid lowering medication. In addition, LA treatments were found to be safe with a low rate of side effects.

Variants in the TGFBR2 kinase domain cause several human diseases and can increase propensity for cancer. The widespread application of next generation sequencing within the setting of Individualized Medicine (IM) is increasing the rate at which TGFBR2 kinase domain variants are being identified. However, their clinical relevance is often uncertain. Consequently, we sought to evaluate the use of molecular modeling and molecular dynamics (MD) simulations for assessing the potential impact of variants within this domain. We documented the structural differences revealed by these models across 57 variants using independent MD simulations for each. Our simulations revealed various mechanisms by which variants may lead to functional alteration; some are revealed energetically, while others structurally or dynamically. We found that the ATP binding site and activation loop dynamics may be affected by variants at positions throughout the structure. This prediction cannot be made from the linear sequence alone. We present our structure-based analyses alongside those obtained using several commonly used genomics-based predictive algorithms. We believe the further mechanistic information revealed by molecular modeling will be useful in guiding the examination of clinically observed variants throughout the exome, as well as those likely to be discovered in the near future by clinical tests leveraging next-generation sequencing through IM efforts.

Lysozyme amyloidosis (ALys) is a rare form of hereditary amyloidosis that typically manifests with renal impairment, gastrointestinal (GI) symptoms, and sicca syndrome, whereas cardiac involvement is exceedingly rare and neuropathy has not been reported. Here, we describe a 40-year-old man with renal impairment, cardiac and GI symptoms, and peripheral neuropathy. Renal biopsy specimen analysis revealed amyloidosis with extensive involvement of glomeruli, vessels, and medulla. Amyloid was also detected in the GI tract. Echocardiographic and electrocardiographic findings were consistent with cardiac involvement. Proteomic analysis of Congo red–positive renal and GI amyloid deposits detected abundant lysozyme C protein. DNA sequencing of the lysozyme gene in the patient and his mother detected a heterozygous c.305T>C alteration in exon 3, which causes a leucine to serine substitution at codon 102 (Human Genome Variation Society nomenclature: p.Leu102Ser; legacy designation: L84S). We also detected the mutant peptide in the proband’s renal and GI amyloid deposits. PolyPhen analysis predicted that the mutation damages the encoded protein. Molecular dynamics simulations suggested that the pathogenesis of ALys p.Leu102Ser is mediated by shifting the position of the central β -hairpin coordinated with an antiparallel motion of the C-terminal helix, which may alter the native-state structural ensemble of the molecule, leading to aggregation-prone intermediates.

Loeys-Dietz syndrome (LDS) is a connective tissue disorder characterized by vascular findings of aneurysm and/or dissection of cerebral, thoracic, or abdominal arteries and skeletal findings. We report a case of a novel pathogenic variant in TGFBR2 and phenotype consistent with classic LDS. The proband was a 10-year-old presenting to the genetics clinic with an enlarged aortic root (Z-scores 5-6), pectus excavatum, and congenital contractures of the right 2nd and 3rd digit. Molecular testing of TGFBR2 was sent to a commercial laboratory and demonstrated a novel, likely pathogenic, variant in exon 4, c.1061T>C, p.(L354P). Molecular modeling reveals alteration of local protein structure as a result of this pathogenic variant. This pathogenic variant has not been previously reported in LDS and thus expands the pathogenic variant spectrum of this condition.

Locus mapping has uncovered diverse etiologies for familial atrial fibrillation (AF), dilated cardiomyopathy (DCM), and mixed cardiac phenotype syndromes, yet the molecular basis for these disorders remains idiopathic in most cases. Whole-exome sequencing (WES) provides a powerful new tool for familial disease gene discovery. Here, synergistic application of these genomic strategies identified the pathogenic mutation in a familial syndrome of atrial tachyarrhythmia, conduction system disease (CSD), and DCM vulnerability. Seven members of a three-generation family exhibited the variably expressed phenotype, three of whom manifested CSD and clinically significant arrhythmia in childhood. Genome-wide linkage analysis mapped two equally plausible loci to chromosomes 1p3 and 13q12. Variants from WES of two affected cousins were filtered for rare, predicted-deleterious, positional variants, revealing an unreported heterozygous missense mutation disrupting the highly conserved kinase domain in TNNI3K. The G526D substitution in troponin I interacting kinase, with the most deleterious SIFT and Polyphen2 scores possible, resulted in abnormal peptide aggregation in vitro and in silico docking models predicted altered yet energetically favorable wild-type mutant dimerization. Ventricular tissue from a mutation carrier displayed histopathological hallmarks of DCM and reduced TNNI3K protein staining with unique amorphous nuclear and sarcoplasmic inclusions. In conclusion, mutation of TNNI3K, encoding a heart-specific kinase previously shown to modulate cardiac conduction and myocardial function in mice, underlies a familial syndrome of electrical and myopathic heart disease. The identified substitution causes a TNNI3K aggregation defect and protein deficiency, implicating a dominant-negative loss of function disease mechanism.

Molecular identification of protein molecules surrounding nanoparticles (NPs) may provide useful information that influences NP clearance, biodistribution, and toxicity. Hence, nanoproteomics provides specific information about the environment that NPs interact with and can therefore report on the changes in protein distribution that occurs during tumorigenesis. Therefore, we hypothesized that characterization and identification of protein molecules that interact with 20 nm AuNPs from cancer and noncancer cells may provide mechanistic insights into the biology of tumor growth and metastasis and identify new therapeutic targets in ovarian cancer. Hence, in the present study, we systematically examined the interaction of the protein molecules with 20 nm AuNPs from cancer and noncancerous cell lysates. Time-resolved proteomic profiles of NP-protein complexes demonstrated electrostatic interaction to be the governing factor in the initial time-points which are dominated by further stabilization interaction at longer time-points as determined by ultraviolet–visible spectroscopy (UV–vis), dynamic light scattering (DLS), ζ-potential measurements, transmission electron microscopy (TEM), and tandem mass spectrometry (MS/MS). Reduction in size, charge, and number of bound proteins were observed as the protein-NP complex stabilized over time. Interestingly, proteins related to mRNA processing were overwhelmingly represented on the NP-protein complex at all times. More importantly, comparative proteomic analyses revealed enrichment of a number of cancer-specific proteins on the AuNP surface. Network analyses of these proteins highlighted important hub nodes that could potentially be targeted for maximal therapeutic advantage in the treatment of ovarian cancer. The importance of this methodology and the biological significance of the network proteins were validated by a functional study of three hubs that exhibited variable connectivity, namely, PPA1, SMNDC1, and PI15. Western blot analysis revealed overexpression of these proteins in ovarian cancer cells when compared to normal cells. Silencing of PPA1, SMNDC1, and PI15 by the siRNA approach significantly inhibited proliferation of ovarian cancer cells and the effect correlated with the connectivity pattern obtained from our network analyses.

The role of structure and dynamics in mechanisms for RNA becomes increasingly important. Computational approaches using simple dynamics models have been successful at predicting the motions of proteins and are often applied to ribonucleo-protein complexes but have not been thoroughly tested for well-packed nucleic acid structures. In order to characterize a true set of motions, we investigate the apparent motions from 16 ensembles of experimentally determined RNA structures. These indicate a relatively limited set of motions that are captured by a small set of principal components (PCs). These limited motions closely resemble the motions computed from low frequency normal modes from elastic network models (ENMs), either at atomic or coarse-grained resolution. Various ENM model types, parameters, and structure representations are tested here against the experimental RNA structural ensembles, exposing differences between models for proteins and for folded RNAs. Differences in performance are seen, depending on the structure alignment algorithm used to generate PCs, modulating the apparent utility of ENMs but not significantly impacting their ability to generate functional motions. The loss of dynamical information upon coarse-graining is somewhat larger for RNAs than for globular proteins, indicating, perhaps, the lower cooperativity of the less densely packed RNA. However, the RNA structures show less sensitivity to the elastic network model parameters than do proteins. These findings further demonstrate the utility of ENMs and the appropriateness of their application to well-packed RNA-only structures, justifying their use for studying the dynamics of ribonucleo-proteins, such as the ribosome and regulatory RNAs.

Methylmercury (MeHg) is a highly toxic environmental contaminant that produces neurological and developmental impairments in animals and humans. Although its neurotoxic properties have been widely reported, the molecular mechanisms by which MeHg enters the cells and exerts toxicity are not yet completely understood. Taking into account that MeHg is found mostly bound to sulfhydryl-containing molecules such as cysteine in the environment and based on the fact that the MeHg-cysteine complex (MeHg-S-Cys) can be transported via the L-type neutral amino acid carrier transport (LAT) system, the potential beneficial effects of L-methionine (L-Met, a well known LAT substrate) against MeHg (administrated as MeHg-S-Cys)-induced neurotoxicity in mice were investigated. Mice were exposed to MeHg (daily subcutaneous injections of MeHg-S-Cys, 10 mg Hg/kg) and/or L-Met (daily intraperitoneal injections, 250 mg/kg) for 10 consecutive days. After treatments, the measured hallmarks of toxicity were mostly based on behavioral parameters related to motor performance, as well as biochemical parameters related to the cerebellar antioxidant glutathione (GSH) system. MeHg significantly decreased motor activity (open-field test) and impaired motor performance (rota-rod task) compared with controls, as well as producing disturbances in the cerebellar antioxidant GSH system. Interestingly, L-Met administration did not protect against MeHg-induced behavioral and cerebellar changes, but rather increased motor impairments in animals exposed to MeHg. In agreement with this observation, cerebellar levels of mercury (Hg) were higher in animals exposed to MeHg plus L-Met compared to those only exposed to MeHg. However, this event was not observed in kidney and liver. These results are the first to demonstrate that L-Met enhances cerebellar deposition of Hg in mice exposed to MeHg and that this higher deposition may be responsible for the greater motor impairment observed in mice simultaneously exposed to MeHg and L-Met.

The structure of hydrogenated amorphous silicon films is investigated by Raman spectroscopy and X-ray diffraction. Raman spectroscopy probes the phonon density of states, whereas X-ray diffraction measures the distribution of the electron density. Yet, both methods can yield information on the microstructure of the material represented by certain parameters like, e.g., the position or the width of the transverse optical phonon or the width of the first scattering peak. Interdependences between these parameters are investigated and evaluated. A correlation was found between the structural disorder and the relative efficiency loss caused by the Staebler-Wronski effect for intrinsic films applied as absorbing layers in solar cells. This correlation could be used to estimate the solar cell degradation without time-consuming light-soaking experiments.

Background Cervical dystonias have a variable presentation and underlying etiology, but collectively represent the most common form of focal dystonia. There are a number of known genetic forms of dystonia (DYT1-27); however the heterogeneity of disease presentation does not always make it easy to categorize the disease by phenotype-genotype comparison. Case presentation In this report, we describe a 53-year-old female who presented initially with hand tremor following a total hip arthroplasty. The patient developed a mixed hyperkinetic disorder consisting of chorea, dystonia affecting the upper extremities, dysarthria, and blepharospasm. Whole exome sequencing of the patient revealed a novel heterozygous missense variant (Chr11(GRCh38): g.26525644C > G; NM_031418.2(ANO3): c.702C > G; NP_113606.2. p.C234W) in exon 7 in the ANO3 gene. Conclusions ANO3 encodes anoctamin-3, a Ca+2-dependent phospholipid scramblase expressed in striatal-neurons, that has been implicated in autosomal dominant craniocervical dystonia (Dystonia-24, DYT24, MIM# 615034). To date, only a handful of cases of DYT-24 have been described in the literature. The complex clinical presentation of the patient described includes hyperkinesias, complex motor movements, and vocal tics, which have not been reported in other patients with DYT24. This report highlights the utility of using clinical whole exome sequencing in patients with complex neurological phenotypes that would not normally fit a classical presentation of a defined genetic disease. Electronic supplementary material The online version of this article (doi:10.1186/s12881-016-0354-7) contains supplementary material, which is available to authorized users.

Mitochondrial disorders are caused by nuclear and mitochondrial pathogenic variants leading to defects in mitochondrial function and cellular respiration. Recently, the nuclear-encoded mitochondrial fusion gene MSTO1 (Misato 1) has been implicated in mitochondrial myopathy and ataxia. Here we report on a 30-yr-old man presenting with a maternally inherited NM_018116.3:c.651C>G, p.F217L missense variant as well as a paternally inherited arr[GRCh37] 1q22(155581773_155706887) × 1 deletion encompassing exons 7–14 of MSTO1. His phenotype included muscle weakness, hypotonia, early motor developmental delay, pectus excavatum, and scoliosis. Testing revealed elevated plasma creatine kinase, and electromyogram results were consistent with longstanding generalized myopathy. These phenotypic features overlap well with previously reported patients harboring biallelic MSTO1 variants. Additionally, our patient presents with dysphagia and restrictive lung disease, not previously reported for MSTO1-associated disorders. The majority of patients with disease-associated variants in MSTO1 present with biallelic variants suggesting autosomal recessive inheritance; however, one family has been reported with a single variant and presumed autosomal dominant inheritance. The pattern of inheritance we observed is consistent with the majority of previous reports suggesting an autosomal recessive disorder. We add to our knowledge of the syndrome caused by variants in MSTO1 and provide additional evidence supporting autosomal recessive inheritance. We also describe phenotypic features not reported in previous cases, although further research is needed to confirm they are associated with defects in MSTO1.

Background Identifying the biologic functions of groups of genes identified in high-throughput studies currently requires considerable time and/or bioinformatics experience. This is due in part to each resource housed within separate databases, requiring users to know about them, and integrate across them. Time consuming and often repeated for each study, integrating across resources and merging with data under study is an increasingly common bioinformatics task. Methods We developed an open-source R software package for assisting researchers in annotating their genesets with functions, pathways, and their interconnectivity across a diversity of network resources. Results We present rapid integration of term annotation and network resources (RITAN) for the rapid and comprehensive annotation of a list of genes using functional term and pathway resources and their relationships among each other using multiple network biology resources. Currently, and to comply with data redistribution policies, RITAN allows rapid access to 16 term annotations spanning gene ontology, biologic pathways, and immunologic modules, and nine network biology resources, with support for user-supplied resources; we provide recommendations for additional resources and scripts to facilitate their addition to RITAN. Having the resources together in the same system allows users to derive novel combinations. RITAN has a growing set of tools to explore the relationships within resources themselves. These tools allow users to merge resources together such that the merged annotations have a minimal overlap with one another. Because we index both function annotation and network interactions, the combination allows users to expand small groups of genes using links from biologic networks—either by adding all neighboring genes or by identifying genes that efficiently connect among input genes—followed by term enrichment to identify functions. That is, users can start from a core set of genes, identify interacting genes from biologic networks, and then identify the functions to which the expanded list of genes contribute. Conclusion We believe RITAN fills the important niche of bridging the results of high-throughput experiments with the ever-growing corpus of functional annotations and network biology resources. Availability Rapid integration of term annotation and network resources is available as an R package at github.com/MTZimmer/RITAN and BioConductor.org.

Recent evidence suggests that genomic variations in cancer predisposition genes are found at higher prevalence in the general population. However, currently, only a handful of genomic variants in these genes are classified as pathogenic with certainty, leaving a significant number classified as variant of unknown significance (VUS) in terms of their potential pathogenicity. Addressing this problem is of significant relevance for improving cancer screening, genetic counseling, and in some cases therapy. Consequently, the GOAL of the current study was to evaluate genomic variations in pancreatic ductal adenocarcinoma (PDAC) predisposition genes from affected patients. We developed and validated the MCW PDAC Germline AmpliSeq Panel, which assessed variation in 53 cancer predisposition genes, including those from hereditary cancers, chronic pancreatitis, DNA damage repair and metabolism. The target DNA panel was amplified and a library was prepared according to the AmpliSeq for Illumina Custom Panel kit. Paired-end, 2x300bp read sequencing was performed at a depth of at least 500X using the MiSeq platform. Variant calling was performed with the Genome Analysis Toolkit (GATK) v3.7 Haplotype Caller. The protein coding effect of genomic variants was annotated using SNPEff and Ensembl canonical transcripts. We annotated variants with their population allele frequency from GnomAD, cancer incidence from COSMIC, and hereditary disease association from ClinVar and HGMD, using the BioR toolkit.A total of 5,658 variants were found in 545 patients representing 4,087 single-nucleotide variants (SNVs) and 1,146 insertion/deletion variants (indels). Among these variants, we found that 483 were seen previously in the COSMIC database, most of which were associated with ‘carcinoma’ primary histology. When considering all variants regardless of their impact, the genes with variants in the highest number of subjects was POLE, followed by APC, BARD1, BRCA2, ATM, and PMS2. APChad the highest number of coding variants across all samples, followed by PMS2, BRCA1, ATM, BRCA2, and BARD1. Lastly, 18 variants (0.31%) have been previously identified as pathogenic, likely pathogenic, or disease-causing variations for pancreatic cancer, while 231 (4.08%) represented VUS. In summary, ourfindings support the existence of wide genomic variation in PDAC-predisposition genes. Identified variants include some of uncertain significance, which warrant future functional studies to better understand their pathogenic potential. Combined, these results raise the possibility that some VUS may predispose to PDAC. Citation Format: Jenica Abrudan, Susan Tsai, Wendy Demos, Michael T. Zimmermann, Michael Tschannen, Jennifer Geurts, Angela Mathison, Gwen Lomberk, Douglas Evans, Raul Urrutia. Genomic variation in PDAC-predisposing genes identified using the MCW germline exome panel [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4163.

Single-chamber processes for the deposition of high efficiency thin-film silicon tandem cells of an a-Si:H p-i-n (top cell)/μc-Si:H p-i-n (bottom cell) structure involving short fabrication time are reported. An industry relevant reactor and an excitation frequency of 13.56 MHz were used. The conversion efficiency is found to be highly sensitive to dopant cross contamination into the μc-Si:H i-layer of the bottom cell and within the n/p-interface of the tunnel recombination junction (TRJ). Different reactor treatments at the p/i-interfaces of the top and bottom cells and at the n/p-interface of the TRJ were applied, aiming to prevent dopant cross contamination. The phosphorus and the boron concentrations were evaluated by secondary ion mass spectrometry measurements. Phosphorus cross contamination after TRJ n-layer deposition is found to result in significant n-type doping of the μc-Si:H i-layer of the bottom cell if no reactor treatment is applied. In situ reactor treatment via an Ar flush and pumping step of 15 min applied at the n/p-interface of TRJ results in reduction of the μc-Si:H i-layer phosphorus concentration to values below 1017 cm− 3. A conversion efficiency of 11.8% for such tandem cells is demonstrated. Shorter interface treatment time with phosphorus concentrations in the μc-Si:H i-layer of about 5 × 1017 cm− 3 results in lower conversion efficiencies of 10.6%, mainly due to the decrease of open-circuit voltage and fill factor.

In this study angular resolved scattering measurements are used to monitor the surface texture properties of sputter-etched ZnO:Al and to identify the influences of process parameter changes on the surface texture. Variations in pressure and temperature are possible drifts in the industrial fabrication that can influence the ZnO:Al properties. Therefore – with respect to industrial relevance – this study focuses on the influence of these parameters. Deposition parameter dependent trends in the angular resolved scattering are studied. Correlations between changes in the results of the angular resolved scattering measurements and the performance of a-Si:H/μc-Si:H tandem solar cells are shown. Additionally, it is demonstrated that the measurements can be used to optimize the surface texture of ZnO:Al for single-junction μc-Si:H solar cells by adjusting the deposition conditions according to the previously identified trends.

Die Betriebsfuhrung elektrischer Transport- und Verteilnetze wird zunehmend dynamischer. Grunde hierfur sind einerseits die Herausforderungen durch hoch ausgelastete Netze sowie volatile Einspeisung, auf die die Netzbetreiber rechtzeitig reagieren mussen, andererseits der zunehmende Einsatz schnell regelbarer Betriebsmittel und leistungsstarker Kommunikations- und Informationstechnik. Um intelligente Entscheidungsverfahren fur dynamische Systemeingriffe zu entwickeln, mussen solche Applikationen zunachst in eine dynamische Simulation des elektrischen Energiesystems eingebunden werden. In diesem Beitrag werden zwei Realisierungsmoglichkeiten zur Einbindung externer Softwaretools in die elektromechanische Simulation des verbreiteten kommerziellen Energiesystemsimulators DIgSILENT PowerFactory vorgestellt. Hierbei wird exemplarisch die Einbindung eines Multiagentensystems zur Koordination von Leistungsflussreglern gezeigt. Neben der Implementierung werden vergleichende Simulationsergebnisse bei Nutzung der beiden Schnittstellen und ermittelte Leistungswerte prasentiert.

Prednisolone causes hyperglycaemia predominantly between midday and midnight. Consequently, glargine-based basal-bolus insulin regimens may under treat daytime hyperglycaemia and cause nocturnal hypoglycaemia. We investigated whether an isophane-based insulin regimen is safer and more effective than a glargine-based regimen in hospitalized patients.Fifty inpatients prescribed ≥20 mg/day prednisolone acutely with (1) finger prick blood glucose level (BGL) ≥15 mmol/L or (2) BGLs ≥10 mmol/L within the previous 24 hours were randomized to either insulin isophane or glargine before breakfast and insulin aspart before meals. The initial daily insulin dose was 0.5 U/kg bodyweight or 130% of the current daily insulin dose. Glycaemic control was assessed using a continuous glucose monitoring system.On Day 1, there were no significant differences in percentage of time outside a target glucose range of 4 to 10 mmol/L (41.3% ± 5.5% vs 50.0% ± 5.7%, P = .28), mean daily glucose (10.2 ± 0.7 vs 10.8 ± 0.8 mmol/L, P = .57) or glucose4 mmol/L (2.2% ± 1.1% vs 2.0% ± 1.3%, P = .92) in patients randomized to isophane and glargine. In patients treated for 3 days, the prednisolone dose was reduced ( P = .02) and the insulin dose was increased over time ( P = .02), but the percentage of time outside the 4 to 10 mmol/L glucose range did not differ over time ( P = .45) or between groups ( P = .24).There were no differences in the efficacy or safety of the isophane and glargine-based insulin regimens. We recommend an initial daily insulin dose of 0.5 units/kg bodyweight if not on insulin, a greater than 30% increase in pre-prednisolone insulin dose and larger insulin dose adjustments in patients with prednisolone-induced hyperglycaemia.

The development of a humoral immune response to influenza vaccines occurs on a multisystems level. Due to the orchestration required for robust immune responses when multiple genes and their regulatory components across multiple cell types are involved, we examined an influenza vaccination cohort using multiple high-throughput technologies. In this study, we sought a more thorough understanding of how immune cell composition and gene expression relate to each other and contribute to interindividual variation in response to influenza vaccination. We first hypothesized that many of the differentially expressed (DE) genes observed after influenza vaccination result from changes in the composition of participants’ peripheral blood mononuclear cells (PBMCs), which were assessed using flow cytometry. We demonstrated that DE genes in our study are correlated with changes in PBMC composition. We gathered DE genes from 128 other publically available PBMC-based vaccine studies and identified that an average of 57% correlated with specific cell subset levels in our study (permutation used to control false discovery), suggesting that the associations we have identified are likely general features of PBMC-based transcriptomics. Second, we hypothesized that more robust models of vaccine response could be generated by accounting for the interplay between PBMC composition, gene expression, and gene regulation. We employed machine learning to generate predictive models of B-cell ELISPOT response outcomes and hemagglutination inhibition (HAI) antibody titers. The top HAI and B-cell ELISPOT model achieved an area under the receiver operating curve (AUC) of 0.64 and 0.79, respectively, with linear model coefficients of determination of 0.08 and 0.28. For the B-cell ELISPOT outcomes, CpG methylation had the greatest predictive ability, highlighting potentially novel regulatory features important for immune response. B-cell ELISOT models using only PBMC composition had lower performance (AUC = 0.67), but highlighted well-known mechanisms. Our analysis demonstrated that each of the three data sets (cell composition, mRNA-Seq, and DNA methylation) may provide distinct information for the prediction of humoral immune response outcomes. We believe that these findings are important for the interpretation of current omics-based studies and set the stage for a more thorough understanding of interindividual immune responses to influenza vaccination.

The goal of annual influenza vaccination is to reduce mortality and morbidity associated with this disease through the generation of protective immune responses. The objective of the current study was to examine markers of immunosenescence and identify immunosenescence-related differences in gene expression, gene regulation, cytokine secretion, and immunologic changes in an older study population receiving seasonal influenza A/H1N1 vaccination. Surprisingly, prior studies in this cohort revealed weak correlations between immunosenescence markers and humoral immune response to vaccination. In this report we further examined the relationship of each immunosenescence marker (age, T cell receptor excision circle frequency, telomerase expression, percentage of CD28- CD4+ T cells, percentage of CD28- CD8+ T cells, and the CD4/CD8 T cell ratio) with additional markers of immune response (serum cytokine and chemokine expression) and measures of gene expression and/or regulation. Many of the immunosenescence markers indeed correlated with distinct sets of individual DNA methylation sites, miRNA expression levels, mRNA expression levels, serum cytokines, and leukocyte subsets. However, when the individual immunosenescence markers were grouped by pathways or functional terms, several shared biological functions were identified: antigen processing and presentation pathways, MAPK, mTOR, TCR, BCR, and calcium signaling pathways, as well as key cellular metabolic, proliferation and survival activities. Furthermore, the percent of CD4+ and/or CD8+ T cells lacking CD28 expression also correlated with miRNAs regulating clusters of genes known to be involved in viral infection. Integrated (DNA methylation, mRNA, miRNA, and protein levels) network biology analysis of immunosenescence-related pathways and genesets identified both known pathways (e.g., chemokine signaling, CTL and NK cell activity), as well as a gene expression module not previously annotated with a known function. These results may improve our ability to predict immune responses to influenza and aid in new vaccine development, and highlight the need for additional studies to better define and characterize immunosenescence.

Population-based studies have revealed 2–10% measles vaccine failure rate even after two vaccine doses. While the mechanisms behind this remain unknown, we hypothesized that host genetic factors are likely to be involved. We performed a genome-wide association study of measles specific neutralizing antibody and IFNγ ELISPOT response in a combined sample of 2872 subjects. We identified two distinct chromosome 1 regions (previously associated with MMR-related febrile seizures), associated with vaccine-induced measles neutralizing antibody titers. The 1q32 region contained 20 significant SNPs in/around the measles virus receptor-encoding CD46 gene, including the intronic rs2724384 (p value = 2.64 × 10−09) and rs2724374 (p value = 3.16 × 10−09) SNPs. The 1q31.1 region contained nine significant SNPs in/around IFI44L, including the intronic rs1333973 (p value = 1.41 × 10−10) and the missense rs273259 (His73Arg, p value = 2.87 × 10−10) SNPs. Analysis of differential exon usage with mRNA-Seq data and RT-PCR suggests the involvement of rs2724374 minor G allele in the CD46 STP region exon B skipping, resulting in shorter CD46 isoforms. Our study reveals common CD46 and IFI44L SNPs associated with measles-specific humoral immunity, and highlights the importance of alternative splicing/virus cellular receptor isoform usage as a mechanism explaining inter-individual variation in immune response after live measles vaccine.

With the approval of new direct acting antiviral agents (DAA), therapeutic options for patients with chronic hepatitis C virus (HCV) infection are now generally available before and after liver transplantation (LT). Interferon-free DAA regimens are highly effective therapies and provide a good safety profile. However, the body of clinical evidence in this patient population is limited and the best treatment strategies for patients on the waiting list with (de)compensated cirrhosis and after LT are not well defined. The following recommendations for antiviral therapy in the context of LT are based on the currently available literature and clinical experience of experts in the field, and have been discussed in an expert meeting. The aim of this article is to guide clinicians in the decision making when treating patients before and after LT with DAAs.

The new BGO-OD experiment at the electron accelerator ELSA, of the University of Bonn, is designed to study the reaction dynamics of nucleon excitations in meson photoproduction. It consists of a central BGO calorimeter with a magnetic spectrometer in forward direction. The physics programme includes the measurement of polarisation observables using linearly and circularly polarised photon beams. Linear polarisation is obtained by coherent bremsstrahlung off a diamond crystal, and circular polarisation is obtained via bremsstrahlung from longitudinally polarised electrons. The degree of linear polarisation is determined from the bremsstrahlung spectrum itself. To determine the polarisation of the circularly polarised photon beam, the polarisation of the electron beam is measured by a Moller polarimeter. As a preliminary consistency check, the (linear) polarisation observable, Σ, was compared to world data for π^0 and η photoproduction. To determine the degree of circular polarisation, a Moller polarimeter was setup and first measurements of the electron beam polarisation performed.

Clusters of genes in co-expression networks are commonly used as functional units for gene set enrichment detection and increasingly as features (attribute construction) for statistical inference and sample classification. One of the practical challenges of clustering for these purposes is to identify an optimal partition of the network where the individual clusters are neither too large, prohibiting interpretation, nor too small, precluding general inference. Newman Modularity is a spectral clustering algorithm that automatically finds the number of clusters, but for many biological networks the cluster sizes are suboptimal. In this work, we generalize Newman Modularity to incorporate information from indirect paths in RNA-Seq co-expression networks. We implement a merge-and-split algorithm that allows the user to constrain the range of cluster sizes: large enough to capture genes in relevant pathways, yet small enough to resolve distinct functions. We investigate the properties of our recursive indirect-pathways modularity (RIP-M) and compare it with other clustering methods using simulated co-expression networks and RNA-seq data from an influenza vaccine response study. RIP-M had higher cluster assignment accuracy than Newman Modularity for finding clusters in simulated co-expression networks for all scenarios, and RIP-M had comparable accuracy to Weighted Gene Correlation Network Analysis (WGCNA). RIP-M was more accurate than WGCNA for modest hard thresholds and comparable for high, while WGCNA was slightly more accurate for soft thresholds. In the vaccine study data, RIP-M and WGCNA enriched for a comparable number of immunologically relevant pathways.

To assess gene signatures related to humoral response among healthy older subjects following seasonal influenza vaccination, we studied 94 healthy adults (50–74 years old) who received one documented dose of licensed trivalent influenza vaccine containing the A/California/7/2009 (H1N1)-like virus strain. Influenza-specific antibody (HAI) titer in serum samples and next-generation sequencing on PBMCs were performed using blood samples collected prior to (Day 0) and at two timepoints after (Days 3 and 28) vaccination. We identified a number of uncharacterized genes (ZNF300, NUP1333, KLK1 and others) and confirmed previous studies demonstrating specific genes/genesets that are important mediators of host immune responses and that displayed associations with antibody response to influenza A/H1N1 vaccine. These included interferon-regulatory transcription factors (IRF1/IRF2/IRF6/IRF7/IRF9), chemokine/chemokine receptors (CCR5/CCR9/CCL5), cytokine/cytokine receptors (IFNG/IL10RA/TNFRSF1A), protein kinases (MAP2K4/MAPK3), growth factor receptor (TGFBR1). The identification of gene signatures associated with antibody response represents an early stage in the science for which further research is needed. Such research may assist in the design of better vaccines to facilitate improved defenses against new influenza virus strains, as well as better understanding the genetic drivers of immune responses.

Background Studies suggest that the recall-based humoral immune responses to influenza A/H1N1 originates from activated memory B cells. The aim of this study was to identify baseline, early and late blood transcriptional signatures (in peripheral blood mononuclear cells/PBMCs) associated with memory B cell response following influenza vaccination. Methods We used pre- and post-vaccination mRNA-Seq transcriptional profiling on samples from 159 subjects (50–74 years old) following receipt of seasonal trivalent influenza vaccine containing the A/California/7/2009/H1N1-like virus, and penalized regression modeling to identify associations with influenza A/H1N1-specific memory B cell ELISPOT response after vaccination. Results Genesets and genes (p-value range 7.92E−08 to 0.00018, q-value range 0.00019–0.039) demonstrating significant associations (of gene expression levels) with memory B cell response suggest the importance of metabolic (cholesterol and lipid metabolism-related), cell migration/adhesion, MAP kinase, NF-kB cell signaling (chemokine/cytokine signaling) and transcriptional regulation gene signatures in the development of memory B cell response after influenza vaccination. Conclusion Through an unbiased transcriptome-wide profiling approach, our study identified signatures of memory B cell response following influenza vaccination, highlighting the underappreciated role of metabolic changes (among the other immune function-related events) in the regulation of influenza vaccine-induced immune memory.

Identification of non-coding RNAs (ncRNAs) has been significantly improved over the past decade. On the other hand, semantic annotation of ncRNA data is facing critical challenges due to the lack of a comprehensive ontology to serve as common data elements and data exchange standards in the field. We developed the Non-Coding RNA Ontology (NCRO) to handle this situation. By providing a formally defined ncRNA controlled vocabulary, the NCRO aims to fill a specific and highly needed niche in semantic annotation of large amounts of ncRNA biological and clinical data.

BGO-OD is a new meson photoproduction experiment at the ELSA facility of Bonn University. It aims at the investigation of non strange and strange baryon excitations, and is especially designed to be able to detect weekly bound meson-baryon type structures. The setup for the BGO-OD experiment is presented, the characteristics of the photon beam and the detector performances are shown and the initial experimental program is discussed.

According to current thinking, natural gas is a fossil energy carrier that, just like oil, underwent organic transformation under high pressure and in the absence of oxygen in the interior of the earth and therefore its composition as a naturally occurring product varies according to its geological source. The main component is always methane, which varies between 75 and 98 %. Other components include nitrogen, ethane and carbon dioxide.

BGO-OD is a newly commissioned experiment to investigate the internal structure of the nucleon, using an energy tagged bremsstrahlung photon beam at the ELSA electron facility. The setup consists of a highly segmented BGO calorimeter surrounding the target, with a particle tracking magnetic spectrometer at forward angles. BGO-OD is ideal for investigating meson photoproduction. The extensive physics programme for open strangeness photoproduction is introduced, and preliminary analysis presented., 6 pages, 4 figures. Proceedings for the 10th International Workshop on the Physics of Excited Nucleons (NSTAR2015)

Background There are insufficient system-wide transcriptomic (or other) data that help explain the observed inter-individual variability in antibody titers after measles vaccination in otherwise healthy individuals. Methods We performed a transcriptome(mRNA-Seq)-profiling study after in vitro viral stimulation of PBMCs from 30 measles vaccine recipients, selected from a cohort of 764 schoolchildren, based on the highest and lowest antibody titers. We used regression and network biology modeling to define markers associated with neutralizing antibody response. Results We identified 39 differentially expressed genes that demonstrate significant differences between the high and low antibody responder groups (p-value≤0.0002, q-value≤0.092), including the top gene CD93 (p

A full understanding of cell mechanics requires knowledge of both translational and rotational dynamics. The single particle orientation and rotational tracking (SPORT) technique is combined here with correlation analysis to identify the fundamental rotational modes: in-plane rotation and out-of-plane tilting, as well as other more complex rotational patterns, from the vast image data captured at a temporal resolution of 5 ms for single gold nanorod probes in live cell imaging experiments. The unique capabilities of visualizing and understanding rotational motions of functional nanoparticles on live cell membranes allow correlation of the rotational and translational dynamics in unprecedented detail and provide new insights into complex membrane processes. Particles with functionalized surfaces, which interact with the membrane in fundamentally different ways, can exhibit distinct rotational modes and are, for the first time, directly visualized, and these show the early events for membrane approach and attachment.

Boron (B) and phosphorus (P) cross-contamination for single-chamber deposited a-Si:H, μc-Si:H, and a-Si:H/μc-Si:H tandem solar cells has been investigated by studying their impact on the different layers of solar cells. To reduce the B and P cross-contamination into the i-layer and p-layer, respectively, to a tolerable level, for a-Si:H and μc-Si:H cells a 15' evacuation cycle prior to the i-layer deposition is applied. The effect of P cross-contamination into the i-layer is strongly reduced by the p-layer deposition and a 15’ evacuation cycle prior to the i-layer deposition. The p-layer is assumed to cover up or to fix (in form of P-B complexes) most of the P at the chamber walls. This leads to high quality μc-Si:H cells and a-Si:H cells with only slightly reduced performance. Here, a soft-start of the a-Si:H i-layer led to high quality cells, presumably due to reduced P recycling. Further, there is no need to clean the process chamber with, e.g. NF3, after each p-layer, as applied in many industrial processes. Instead, many cells are deposited without cleaning the process chamber. We established a single-chamber tandem cell process with 15' evacuation cycles prior to the μc-Si:H p-layer and to each i-layer with a cell efficiency of ~ 11.1%.

Hydrogenated amorphous silicon (a-Si:H) is conventionally deposited using static plasma-enhanced chemical vapor deposition (PECVD) processes. In this work, a very high frequency (VHF) dynamic deposition technique is presented, on the basis of linear plasma sources. This configuration deploys a simple reactor design and enables continuous deposition processes, leading to a high throughput. Hence, this technique may facilitate the use of flexible substrates. As a result, the production costs of thin-film silicon solar cells could be reduced significantly. We found a suitable regime for the homogeneous deposition of a-Si:H layers for growth rates from 0.35–1.1 nm/s. The single layer properties as well as the performance of corresponding a-Si:H solar cells are investigated and compared with a state-of-the-art radio frequency (RF) PECVD regime. By analyzing the Fourier transform infrared spectroscopy spectra of single layers, we found an increasing hydrogen concentration with deposition rate for both techniques, which is in agreement with earlier findings. At a given growth rate, the hydrogen concentration was at the same level for intrinsic layers deposited by RF-PECVD and VHF-PECVD. The initial efficiency of the corresponding p–i–n solar cells ranged from 9.6% at a deposition rate of 0.2 nm/s (RF regime) to 8.9% at 1.1 nm/s (VHF regime). After degradation, the solar cell efficiency stabilized between 7.8% and 5.9%, respectively. The solar cells incorporating intrinsic layers grown dynamically using the linear plasma sources and very high frequencies showed a higher stabilized efficiency and lower degradation loss than solar cells with intrinsic layers grown statically by RF-PECVD at the same deposition rate. Copyright © 2012 John Wiley & Sons, Ltd.

We investigate the relationship between the motions of the same peptide loop segment incorporated within a protein structure and motions of free or end-constrained peptides. As a reference point we also compare against alanine chains having the same length as the loop. Both the analysis of atomic molecular dynamics trajectories and structure-based elastic network models, reveal no general dependence on loop length or on the number of solvent exposed residues. Rather, the whole structure affects the motions in complex ways that depend strongly and specifically on the tertiary structure of the whole protein. Both the Elastic Network Models and Molecular Dynamics confirm the differences in loop dynamics between the free and structured contexts; there is strong agreement between the behaviors observed from molecular dynamics and the elastic network models. There is no apparent simple relationship between loop mobility and its size, exposure, or position within a loop. Free peptides do not behave the same as the loops in the proteins. Surface loops do not behave as if they were random coils, and the tertiary structure has a critical influence upon the apparent motions. This strongly implies that entropy evaluation of protein loops requires knowledge of the motions of the entire protein structure.

For deposition of a-Si:H p–i–n solar cells, a single-chamber plasma enhanced chemical vapor deposition process at the frequency of 13.56 MHz is developed. A 40×40 cm² deposition chamber, which represents typical industry reactors equipped with showerhead electrodes is employed. Various methods are applied to reduce the boron-cross contamination from the boron-doped p-layer into the intrinsic layer, which is considered to reduce solar cell efficiency by losses especially in the short wavelength range. Three different device configurations and four different chamber treatment methods are studied, aimed to reach stable device efficiencies comparable to multi-chamber systems at minimum chamber treatment effort and treatment time. An ex-situ CO2–plasma treatment applied after deposition of the p-doped layer is found to be effective to reduce boron-cross contamination. However, this CO2-treatment is a time-consuming process step for production. We found a less time consuming treatment: by a chamber evacuation to 9×10−7 mbar subsequent to p-layer deposition. Initial and stable efficiencies of 10.2% and 7.7%, respectively, were obtained. This latter treatment results in a sharp drop of the boron concentration from ∼5×1020 cm−3 in the p-doped layer to ∼1017 cm−3 in the intrinsic layer. For comparison of different reactor geometries and their influence on the cross-contamination we used a small-area (10×10 cm2) lab-type reactor.

Thin‑film silicon solar cells based on hydrogenated amorphous silicon (a‑Si:H) and hydrogenated microcrystalline silicon (μc‑Si:H) absorber layers are typically deposited using static plasma-enhanced chemical vapor deposition (PECVD) processes. It has been found that the use of very‑high frequencies (VHF) is beneficial for the material quality at high deposition rates when compared to radio-frequency (RF) processes. In the present work a dynamic VHF‑PECVD technique using linear plasma sources is developed. The linear plasma sources facilitate the use of very-high excitation frequencies on large electrode areas without compromising on the homogeneity of the deposition process. It is shown that state-of-the-art a‑Si:H and μc‑Si:H single-junction solar cells can be deposited incorporating intrinsic layers grown dynamically by VHF-PECVD at 0.35 nm/s and 0.95 nm/s, respectively.

Erdheim-Chester disease (ECD) is a rare histocytic disorder. We report a case of a 45-year-old male ECD patient with severe clinical manifestation (urinary obstruction due to retroperitoneal mass with hydronephrosis, involvement of long bones) and central nervous system involvement (hemiparesis, aphasia and diabetes insipidus). Diagnosis was confirmed by typical clinical, radiological and histological findings. Under immunosuppressive therapy with prednisolone and interleukin-1A receptor antagonist (Anakinra, Kineret, Swedish Orphan Biovitrum AB, Stockholm, Sweden), a rapid improvement of the patients' symptoms and condition was observed. This is the first report of a successful combination therapy of Anakinra and glucocorticoids. Furthermore, current literature about ECD and treatment options are discussed.

The need for recognition of mild cognitive impairment (MCI) in primary care is increasingly discussed because MCI is a risk factor for dementia. General Practitioners (GPs) could play an important role in the detection of MCI since they have regular and long-term contact with the majority of the elderly population. Thus the objective of this study is to find out how well GPs recognize persons with MCI in their practice population. Cross-sectional study. Primary care chart registry sample. 3,242 non-demented GP patients aged 75–89 years. GPs assessed the cognitive status of their patients on the Global Deterioration Scale (GDS). Thereafter, trained interviewers collected psychometric data by interviewing the patients at home. The interview data constitute the basis for the definition of MCI cases (gold standard). The sensitivity of GPs to detect MCI was very low (11–12%) whereas their specificity amounts to 93–94%. Patients with MCI with a middle or high level of education more often got a false negative assignment than patients with a low educational level. The risk of a false positive assignment rose with the patients’ degree of comorbidity. GPs were better at detecting MCI when memory or two and more MCIdomains were impaired. The results show that GPs recognise MCI in a very limited number of cases when based on clinical impression only. A further development of the MCI concept and its operationalisation is necessary. Emphasis should be placed on validated, reliable and standardised tests for routine use in primary care encompassing other than only cognitive domains and on case finding approaches rather than on screening. Then a better attention and qualification of GPs with regard to the recognition of MCI might be achievable.