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We present a detailed simulation study of the signatures from the sequential decays of the triple-strange pbar p -> {\Omega}+{\Omega}- -> K+{\Lambda}barK- {\Lambda} -> K+pbar{\pi}+K-p{\pi}- process in the PANDA central tracking system with focus on hit patterns and precise time measurement. We present a systematic approach for studying physics channels at the detector level and develop input criteria for tracking algorithms and trigger lines. Finally, we study the beam momentum dependence on the reconstruction efficiency for the PANDA detector.

Neurodegenerative diseases likely share common underlying pathobiology. Although prior work has identified susceptibility loci associated with various dementias, few, if any, studies have systematically evaluated shared genetic risk across several neurodegenerative diseases. Using genome-wide association data from large studies (total n = 82,337 cases and controls), we utilized a previously validated approach to identify genetic overlap and reveal common pathways between progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), Parkinson’s disease (PD) and Alzheimer’s disease (AD). In addition to the MAPT H1 haplotype, we identified a variant near the chemokine receptor CXCR4 that was jointly associated with increased risk for PSP and PD. Using bioinformatics tools, we found strong physical interactions between CXCR4 and four microglia related genes, namely CXCL12, TLR2, RALB, and CCR5. Evaluating gene expression from post-mortem brain tissue, we found that expression of CXCR4 and microglial genes functionally related to CXCR4 was dysregulated across a number of neurodegenerative diseases. Furthermore, in a mouse model of tauopathy, expression of CXCR4 and functionally associated genes was significantly altered in regions of the mouse brain that accumulate neurofibrillary tangles most robustly. Beyond MAPT, we show dysregulation of CXCR4 expression in PSP, PD, and FTD brains, and mouse models of tau pathology. Our multi-modal findings suggest that abnormal signaling across a ‘network’ of microglial genes may contribute to neurodegeneration and may have potential implications for clinical trials targeting immune dysfunction in patients with neurodegenerative diseases.

Pesticide exposure is associated with increased risk of Parkinson's disease (PD). We investigated in Egypt whether common variants in genes involved in pesticide detoxification or transport might modify the risk of PD evoked by pesticide exposure. We recruited 416 PD patients and 445 controls. Information on environmental factors was collected by questionnaire-based structured interviews. Candidate single-nucleotide polymorphisms (SNPs) in 15 pesticide-related genes were genotyped. We analyzed the influence of environmental factors and SNPs as well as the interaction of pesticide exposure and SNPs on the risk of PD. The risk of PD was reduced by coffee consumption [OR = 0.63, 95% CI: 0.43-0.90, P = 0.013] and increased by pesticide exposure [OR = 7.09, 95% CI: 1.12-44.01, P = 0.036]. The SNP rs1126680 in the butyrylcholinesterase gene BCHE reduced the risk of PD irrespective of pesticide exposure [OR = 0.38, 95% CI: 0.20-0.70, P = 0.002]. The SNP rs1803274, defining K-variant BCHE, interacted significantly with pesticide exposure (P = 0.007) and increased the risk of PD only in pesticide-exposed individuals [OR = 2.49, 95% CI: 1.50-4.19, P = 0.0005]. The K-variant BCHE reduces serum activity of butyrylcholinesterase, a known bioscavenger for pesticides. Individuals with K-variant BCHE appear to have an increased risk for PD when exposed to pesticides.

The interlayer expanded zeolite COE-4 was synthesized using silylation agents such as dichlorodimethylsilane (DCDMS) as layer linker from layered silicate RUB-36 precursor. Solid-state NMR techniques combined with theoretical calculations have proven to be a useful characterization method to investigate the structure and porosity of the interlayer expanded zeolites. XRD and 29Si MAS NMR results show that after calcination the layer spacing of COE-4 is enlarged by 2.6 A compared with that of RUB-37, indicating that pore windows between the layers are enlarged from 8-membered ring (8-MR) pores to 10-MR pores due to the formation of Si(OH)2 pillar between adjacent layers. Hyperpolarized (HP) 129Xe NMR results indicate that after interlayer expansion, Xe atoms can be adsorbed in the 10-MR channels of COE-4, and the 10-MR channels are homogeneously distributed like ZSM-5. For COE-4, Xe has a stronger interaction with the channel walls containing dual silanol groups. 1H MAS NMR combined with theoretical calculations make a clear assignment of dual silanol groups at 3.3 ppm, and the concentration of dual silanols is 2.2 mmol/g, which is 1–2 orders of magnitude larger than the concentration of the other two types of existing isolated and hydrogen-bonded silanol groups. After introduction of pyridine-d5, one Si–OH from the dual silanol groups has a weak hydrogen bond interaction with pyridine molecule, and the adsorbed pyridine molecule may experience chemical exchange with the other Si–OH of the dual silanol group and therefore 1H NMR signal of dual silanol groups shows a weak broad peak at 5.7 ppm after pyridine adsorption.

BACKGROUND: Progressive supranuclear palsy (PSP) is a neuropathologically defined disease presenting with a broad spectrum of clinical phenotypes. OBJECTIVE: To identify clinical features and investigations that predict or exclude PSP pathology during life, aiming at an optimization of the clinical diagnostic criteria for PSP. METHODS: We performed a systematic review of the literature published since 1996 to identify clinical features and investigations that may predict or exclude PSP pathology. We then extracted standardized data from clinical charts of patients with pathologically diagnosed PSP and relevant disease controls and calculated the sensitivity, specificity, and positive predictive value of key clinical features for PSP in this cohort. RESULTS: Of 4166 articles identified by the database inquiry, 269 met predefined standards. The literature review identified clinical features predictive of PSP, including features of the following 4 functional domains: ocular motor dysfunction, postural instability, akinesia, and cognitive dysfunction. No biomarker or genetic feature was found reliably validated to predict definite PSP. High-quality original natural history data were available from 206 patients with pathologically diagnosed PSP and from 231 pathologically diagnosed disease controls (54 corticobasal degeneration, 51 multiple system atrophy with predominant parkinsonism, 53 Parkinson's disease, 73 behavioral variant frontotemporal dementia). We identified clinical features that predicted PSP pathology, including phenotypes other than Richardson's syndrome, with varying sensitivity and specificity. CONCLUSIONS: Our results highlight the clinical variability of PSP and the high prevalence of phenotypes other than Richardson's syndrome. The features of variant phenotypes with high specificity and sensitivity should serve to optimize clinical diagnosis of PSP. © 2017 International Parkinson and Movement Disorder Society.

Der Beitrag behandelt Doppelstädte anhand von drei Fallbeispielen. Brandenburg an der Havel, Hildesheim und Haithabu stehen nicht nur für verschiedene Zeiträume, sondern reflektieren auch unterschiedliche kulturelle Kontexte. Um diese Städte vergleichbar zu machen, wird abschließend ein Modell präsentiert, welches verschiedene Modi von Doppelstädten beschreibt., This paper examines twin cities using three case studies. Brandenburg an der Havel, Hildesheim, and Haithabu not only reflect different time periods, but also different cultural contexts. In order to make these cities comparable, a model is presented that describes different modes of twin cities.

Burgen, die sich in unmittelbarer Nachbarschaft befinden, werfen die Frage auf, ob zwischen ihnen einst ein engerer Zusammenhang bestanden hat. Man spricht von Mehrfachburgen, wenn mindestens zwei separate, aber benachbarte und zur gleichen Zeit genutzte Burganlagen eine funktionale Einheit darstellten. Die bronzezeitlichen Burgwälle von Lossow und Lebus an der Oder bilden den Ausgangspunkt für eine Untersuchung dieses aus der Bronzezeit und dem Mittelalter bekannten Phänomens. Ein Überblick zu metallzeitlichen Befestigungsanlagen liefert den Kontext, in den sich die konkreten Fallstudien bronzezeitlicher Mehrfachburgen einbinden lassen. Diesen Anlagen werden wiederum mittelalterliche Mehrfachburgen und Doppelstädte in einer Reihe regionaler Untersuchungen gegenübergestellt. So trägt der Band zu einem tieferen Verständnis und einer klareren Terminologie des Phänomens eng benachbarter Burg- und Stadtanlagen bei.

Background and purpose: Mutations in the FUS/TLS have been associated with amyotrophic lateral sclerosis (ALS) in a few percent of patients. Methods: We screened 184 familial (FALS) and 200 sporadic German patients with ALS for FUS/TLS mutations by sequence analysis of exons 5 6 and 13 15. We compared the phenotypes of patients with different FUS/TLS mutations. Results: We identified three missense mutations p.K510R p.R514G p.R521H and the two truncating mutations p.R495X and p.G478LfsX23 in samples from eight pedigrees. Both truncating mutations were associated with young onset and very aggressive disease courses whereas the p.R521H p.R514G and in particular the p.K510R mutation showed a milder phenotype with disease durations ranging from 3years to more than 26years the longest reported for a patient with a FUS/TLS mutation. Also in a pair of monozygous twins with the p.K510R mutation a remarkable similar disease course was observed. Conclusions: Mutations in FUS/TLS account for 8.7 (16 of 184) of FALS in Germany. This is a higher prevalence than reported from other countries. Truncating FUS/TLS mutations result in a more severe phenotype than most missense mutations. The wide phenotypic differences have implications for genetic counselling. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

Corticobasal degeneration (CBD) is a neurodegenerative disorder affecting movement and cognition, definitively diagnosed only at autopsy. Here, we conduct a genome-wide association study (GWAS) in CBD cases (n=152) and 3,311 controls, and 67 CBD cases and 439 controls in a replication stage. Associations with meta-analysis were 17q21 at MAPT (P=1.42 × 10(-12)), 8p12 at lnc-KIF13B-1, a long non-coding RNA (rs643472; P=3.41 × 10(-8)), and 2p22 at SOS1 (rs963731; P=1.76 × 10(-7)). Testing for association of CBD with top progressive supranuclear palsy (PSP) GWAS single-nucleotide polymorphisms (SNPs) identified associations at MOBP (3p22; rs1768208; P=2.07 × 10(-7)) and MAPT H1c (17q21; rs242557; P=7.91 × 10(-6)). We previously reported SNP/transcript level associations with rs8070723/MAPT, rs242557/MAPT, and rs1768208/MOBP and herein identified association with rs963731/SOS1. We identify new CBD susceptibility loci and show that CBD and PSP share a genetic risk factor other than MAPT at 3p22 MOBP (myelin-associated oligodendrocyte basic protein).

Corticobasal degeneration (CBD) is a neurodegenerative disorder affecting movement and cognition, definitively diagnosed only at autopsy. Here, we conduct a genome-wide association study (GWAS) in CBD cases (n=152) and 3,311 controls, and 67 CBD cases and 439 controls in a replication stage. Associations with meta-analysis were 17q21 at MAPT (P=1.42 × 10(-12)), 8p12 at lnc-KIF13B-1, a long non-coding RNA (rs643472; P=3.41 × 10(-8)), and 2p22 at SOS1 (rs963731; P=1.76 × 10(-7)). Testing for association of CBD with top progressive supranuclear palsy (PSP) GWAS single-nucleotide polymorphisms (SNPs) identified associations at MOBP (3p22; rs1768208; P=2.07 × 10(-7)) and MAPT H1c (17q21; rs242557; P=7.91 × 10(-6)). We previously reported SNP/transcript level associations with rs8070723/MAPT, rs242557/MAPT, and rs1768208/MOBP and herein identified association with rs963731/SOS1. We identify new CBD susceptibility loci and show that CBD and PSP share a genetic risk factor other than MAPT at 3p22 MOBP (myelin-associated oligodendrocyte basic protein).

BACKGROUND: A 3.68 Mbp duplication of 8p23.1 defines the 8p23.1 duplication syndrome. The main features of this syndrome are developmental delay and/or learning problems. RESULTS: Here we present a patient with a 1.80 Mbp duplication in 8p23.1 and characteristic signs and symptoms of the syndrome, including delay of motor and speech development and intellectual disability. DISCUSSION: The case indicates that genes within this interval, in particular dosage sensitive genes SOX7 and TNKS1, and possibly MIR124-1 and MIR598 as well suffice to cause the pathognomonic features of the 8p23.1 duplication syndrome.

Vor über 100 Jahren hat Alois Alzheimer zum ersten Mal die später nach ihm benannte Krankheit beschrieben. Wissenschaftlern des Instituts für Humangenetik der Universität Gießen ist es nun in Zusammenarbeit mit einem Kollegen des Hirnforschungsinstituts der Universität Sidney, Australien, gelungen, den Fall der Auguste Deter auch molekular aufzuklären. Die Ergebnisse ihrer Forschungsarbeit wurden Ende 2012 in Lancet Neurology veröffentlicht.

Mc 2009. Microscopy Conference, Graz, Austria. 30 August - 4 September 2009. First Joint Meeting Of Dreiländertagung And Multinational Congress On Microscopy.

Titelblatt und Inhalt I 1\. Einleitung 2 2\. Literaturübersicht 5 3\. Methodik 27 4\. Ergebnisse 33 5\. Diskussion 62 6\. Zusammenfassung 80 7\. Publikationen 82 8\. Literaturverzeichnis 83 Danksagung 98 Eidesstattliche Erklärung 100, Ziel der vorliegenden Arbeit war zu prüfen, wie häufig Multiple Sklerose (MS) Patienten ohne oligoklonale Banden (OB) im Liquor in einer repräsentativen MS Population sind, und ob diese sich bezüglich des Behinderungsgrades, kernspintomographischer Befunde sowie der klinischen Verlausform von Patienten mit sicherer MS mit oligoklonalen Banden im Liquor unterscheiden. Als Datenbasis diente die MUSIS Datenbank des Jüdischen Krankenhauses Berlin, in der prospektiv standardisiert Daten erfasst werden. Aus dieser Datenbank wurden alle Patienten ausgewählt, bei denen keine OB im Liquor nachweisbar waren und die sicher an MS erkrankt waren. Von Januar 1995 bis zum Oktober 2003 wurden insgesamt 1827 MS Patienten auf das Vorhandensein von OB im Liquor untersucht. Siebzig der untersuchten 1827 MS Patienten (3,6 Prozent), deren Liquor auf das Vorhandensein oligoklonaler Banden untersucht wurde, wiesen keine OB im Liquor auf und waren sicher an MS erkrankt. Um mögliche Unterschiede im Behinderungsgrad (EDSS) und der Zahl Gadoliniumaufnehmender Läsionen in der Kernspintomographie zwischen OB negativen und OB positiven MS Patienten zu ermitteln, wurde zu jedem der 70 OB negativen MS Patienten ein OB positiver MS Patient, der eine größtmögliche Übereinstimmung hinsichtlich Alter, Geschlecht, Krankheitsdauer und Alter zu Krankheitsbeginn aufwies, nach einem Zufallsprinzip gefunden. Es konnte ein hochsignifikanter Unterschied im Behinderungsgrad zwischen OB negativen und OB positiven MS Patienten mit gleichem Manifestationsalter, Alter und gleicher Krankheitsdauer gefunden werden (EDSS 2,7 vs. 3,8; p< 0,00001). Einen benignen Krankheitsverlauf (EDSS ≤ 2 nach ≥ 10 Jahren Krankheitsdauer [Pittock et al. 2004]) wiesen 30,4 Prozent der OB negativen MS Patienten auf. In der Gesamtgruppe untersuchter MS Patienten lag dieser Anteil nur bei 19,7%. Zudem konnte gezeigt werden, dass mehr OB positive MS Patienten einen sekundär chronisch progredienten Verlauf aufwiesen. Der höhere EDSS der OB positiven MS Patienten könnte durch die höhere Wahrscheinlichkeit OB positiver MS Patienten erklärt werden, einen sekundär chronisch progredienten Krankheitsverlauf zu entwickeln. Zudem wurden alle verfügbaren Kernspintomographie-Befund Daten der 70 OB negativen und 70 OB positiven MS Patienten, insbesondere hinsichtlich einer Gadoliniumaufnahme, ausgewertet. Es wurde die mittlere Zahl der Gadoliniumaufnehmenden Läsionen pro MRT und Patient berechnet und verglichen. OB negative MS Patienten wiesen im Mittel signifikant weniger Gadoliniumaufnehmenden Läsionen im MRT, als OB positive MS Patienten auf (2,06 vs. 2,88; p= 0,03). Dieser Unterschied könnte eine weitere Ursache für den geringeren Behinderungsgrad der OB negativen MS Patienten sein. Die Zahl der Gadoliniumaufnehmenden Läsionen im MRT korrelierte weder in der Gruppe der OB negativen, noch in der Gruppe der OB positiven MS Patienten mit dem Behinderungsgrad oder der Krankheitsdauer. Es wurden Unterschiede im Alter zu Krankheitsbeginn, Krankheitsdauer und Grad der Behinderung zwischen MS Patienten ohne OB im Liquor und Patienten der Gesamtpopulation untersuchter MS Patienten gefunden. OB negative MS Patienten erkrankten durchschnittlich später als Patienten der untersuchten Gesamtpopulation, hatten eine kürzere Krankheitsdauer und zeigten einen niedrigeren Behinderungsgrad. Außerdem wurden mögliche Korrelationen zwischen einzelnen Liquorparametern bei einer Gruppe von 205 OB positiven MS Patienten, deren Liquor im Liquorlabor der Neurologischen Klinik der Medizinischen Hochschule Hannover analysiert wurde, untersucht. Die Zahl der oligoklonalen Banden korrelierte signifikant mit dem IgG-Index, der Liquorzellzahl, der absoluten intrathekalen IgG-Synthese nach Reiber/Felgenhauer, der prozentualen intrathekalen IgG-Synthese nach Reiber und dem IgG-Quotienten. Dies zeigt, dass die OB Zahl gut mit der intrathekalen Entzündungsaktivität korreliert und von der intrathekal sezerniertem IgG Menge abhängig ist. Eine signifikant negative Korrelation fand sich zwischen der Zahl oligoklonaler Banden im Liquor und dem Alter zum Zeitpunkt der Lumbalpunktion. Je älter die Patienten zum Zeitpunkt der Lumbalpunktion waren, desto weniger OB ließen sich im Liquor nachweisen. Es konnten keine signifikanten Unterschiede zwischen den weiblichen und männlichen MS Patienten bezüglich der Zahl der OB im Liquor, anderen Liquorparametern, dem EDSS und dem Alter zum Zeitpunkt der Lumbalpunktion gefunden werden. Einzig der Albuminquotient war bei den Patientinnen signifikant niedriger als bei den untersuchten Patienten. Die Arbeit bestätigt damit anhand eines großen Patientenkollektives Ergebnisse vorheriger kleinerer Studien [Stendahl-Brodin und Link, 1980; Zeman et al., 1996], wonach Patienten mit einer sicheren MS ohne nachweisbare oligoklonale Banden im Liquor einen relativ benignen Krankheitsverlauf aufweisen. Oligoklonale Banden im Liquor sind ein prognostischer Marker für das Fortschreiten der Erkrankung und das Ausmaß der Behinderung bei Patienten mit einer sicheren MS. Unterschiedliche neuropathologische Muster der MS wurden kürzlich beschrieben [Lucchinetti et al., 2000] und es bleibt abzuwarten, ob MS Patienten ohne oligoklonale Banden im Liquor einer bestimmten Subgruppe zugeordnet werden können., At a time when almost all MS patients receive some kind of immunomodulatory therapy, possible misdiagnoses should be avoided at all means. Therefore the German treatment consensus group insists that the diagnosis of MS should include both MRI and testing for oligoclonal bands (OB) in the cerebrospinal fluid. With modern isoelectric focusing (IEF) techniques OB can be detected in 95 - 100 % of patients with clinically definite MS. The literature on MS cases with negative OB is scarce and inconclusive. Most investigations have been carried out with inadequate methods and/ or insufficient sensitivity. Our objective was to define the frequency of OB negative MS patients in larger case material and to further analyse the differences concerning age at onset, gender, disease course, progression and disability after follow-up between OB negative and OB positive MS patients. Methods: The MS data bank MUSIS of the Jewish hospital in Berlin was reviewed for MS patients, whose CSF and serum had been analysed for oligoclonal IgG bands by IEF between 1995 and 2003. 1827 patients with a diagnosis of MS were identified. CSF analysis of the 70 OB negative MS patients had been performed at N= 24 different laboratories. Gender, age at onset, duration of disease, course of disease and severity (expanded disability status scale, EDSS) were extracted from the data base. Patient follow-up was assessed up to October 2003 and ranged from 1 year to 51 years (mean 14.8, ± 8.4 SD). Further we compared two matched groups of patients - 70 OB negative MS patients versus 70 OB positive MS patients. Matching was performed in the following manner. For each OB negative case we identified a OB positive MS patient of the same gender, age at onset, duration of disease, and of the same diagnostic category. Matching of the RRMS (relapsing and remitting MS) patients to SPMS (secondary progressive MS) was permitted. The patient closest to the index case was selected. Results: In 151/1827 (8.3 %) patients with a tentative diagnosis of MS no OBs were found. Among these 62 had possible MS, six turned out to have an alternative diagnosis (cerebral vasculitis, adrenoleukodystrophy (ALD), Polyneuritis and Myelitis, hydrocephalus internus due to aqueduct stenosis, Morbus Wilson and autoimmun triggered polyneuropathy) and 13 patients had changed to OB positive on a repeat lumbar puncture, leaving 70 patients with definite MS and no OBs (3.8%). Differences between the 70 OB negative and 70 positive MS patients were found regarding EDSS (2.7 versus 3.8, p< 0.00001) and progression index (0.30 versus 0.43, p< 0.01). Discussion: We find that clinical definite MS without OB is rare (3.8%), and should be diagnosed with caution (only 46.4% of all OB negative MS patients were definite MS patients). Despite the problems of a retrospective data collection concerning selection bias and incomplete documentation in medical records, the matched group of positive MS patients represents a good selection of all OB positive MS patients. MS patients in the OB negative group were significantly less disabled than the matched OB positive MS patients (EDSS 2.7 vs. 3.8 p 95 % positive OB results for definite MS patients are acceptable. According to this criterion all the data (except Bergamanschi et al., 2004 and Zeman et al., 1996) in table 1 have to be considered as inadequate. The considerable difficulties associated with the alleged absence of OB are vividly illustrated in the report of Zeman et al. Initially 34/290 (11.7 %) were found to be OB negative, but subsequent reinspection of the foils led to a revision from negative to positive in 14 patients. For eight other patients a new diagnosis was established and 3/6 patients with a repeat lumbar puncture showed OBs on the second occasion. Altogether only 9/290 (3.1 %) remained with trustful negative OB. OBs may sometimes be absent in a small percentage of patients at initial presentation such as optic neuritis (Söderström et al., 1998) or in children (Sindern et al., 1992) and become positive in the course of the disease. The conversion from negative to positive OB was also observed by us for 13 definite MS patients who underwent a second lumbar puncture. However, in most of the cases the change in the OB rating may be explained by a better performance of the second laboratory (11/11 reexamined at the neurochemical laboratory of the medical school Hannover were found to be positive), rather than by the development of an intrathecal IgG response. The minimum number of OB chosen as cut-off may also influence the percentage of MS patients with negative OB. Most authors demand 2-3 OB for a positive rating. The disappointingly low frequency of only 76 % OB positive MS patients ( Pirttilla et al., 1995) may be explained by the unusually high cut-off of 5 OB. Conversely patients with only 1 OB are negative by definition, but show an increased propensity to develop a complete oligoclonal pattern on a repeat lumbar puncture (Davies et al., 2003). Interestingly 4 of the13 MS patients (30.8 %) without OB who were investigated at the Medical School Hannover displayed one OB. Information on the remaining 57 OB negative MS patients was not available from the other laboratories. Despite the drawback that the results for OB had to be assembled from N= 24 different laboratories, the proportion of definite MS patients with negative OB was remarkably low with only 70/1827 (3.8 %). Thus OB negative CDMS is rare and should be diagnosed with caution. In six patients the absence of OB prompted reconsideration of the initial diagnosis of MS which was substituted by cerebral vasculitis, adrenoleukodystrophy (ALD), polyneuritis and myelitis, hydrocephalus internus due to aqueduct stenosis, Morbus Wilson and autoimmun triggered polyneuropathy. If OBs are lacking it is recommended to repeat the laboratory investigations because (1) a false negative result may probably have been reported by a laboratory with suboptimal performance, or (2) an alternative diagnosis should be considered, or (3) OB may develop with time in patients with a short course of suspected MS. Our study supports the conclusion of previous studies [Stendahl-Brodin et al., 1980; Zeman et al., 1996] that the prognosis of true OB negative MS patients is relatively benign. Different neuropathological patterns have recently be defined in MS (Lucchinetti et al., 2000) and it remains to be seen, if MS patients without OBs can be allocated to a certain subgroup. Subanalysis: CSF analysis in 205 patients with multiple sclerosis. Relevance of the number of oligoclonal bands, interrelation of CSF variables and correlation with clinical data Background: Currently investigations of the CSF of patients with MS are gaining renewed interest. While modern methods of CSF analysis are indispensable for making an early and secure diagnosis, they may also turn out to be of value in predicting clinical disease course and response towards different therapies. However, it is rarely recognized that common CSF parameters may show a considerable degree of interrelation. The recently suggested parameter "number of oligoclonal bands" was tested for such dependencies and the correlation of common CSF variables with clinical data was investigated. Methods: In a retrospective analysis the clinical data for 205 patients with definite MS and positive oligoclonal bands (OB) were extracted from the MUSIS data bank at the Jewish Hospital Berlin. Identification of the oligoclonal band pattern was carried out by isoelectric focusing on polyacrylamide gels with silverstaining in one laboratory. Counting of bands was always performed by the same person (U.W.). Results: Mean age of the 144 women and 61 men at the time of lumbar puncture was 41.2 (SD: 11.6) years. Mean cell count amounted to 4.9/µl with 65/174 (37.4 %) showing more than 4 cells/µl. EDSS score at follow-up correlated negatively with the number of cells (r = - 0.292), but not with the number of OB. The CSF/serum quotient for albumin (blood-CSF-barrier) showed a significant correlation with EDSS (r = 0.234, p = 000.1) and was higer in men than in women (p = 0.017). The mean number of CSF restricted OB was 15.2 (SD: 7.8), with a minimum of 2 (set cut-off) and a maximum of 34 OB. Only 7/205 (3.4%) had less than 4 OB. Additional identical OB in serum (oligoclonal pattern type 3) were encountered in 69/205 (33.7 %), but only 25/205 (12.2 %) displayed at least 4 or more identical OB. The mean IgG index was 0.943 and in 119/205 (58%) it was higher than the usual limit of 0.700. The number of OB correlated closely with the IgG index (r = 0.671, p< 0.0001) and more weakly with the cell count (r = 0.292). It showed a slight decrease with age (r = - 0.192). Conclusion: Comparisons between different methods must consider that the number of OB depends (i) on the resolution of the gels and (ii) on the amount of intrathecally synthesized IgG. CSF analysis has the potential to assist in prognosis and therapy, but a multifactorial approach must be used, including parameters for demyelination, neuronal and axonal damage.

In this article we analyze the risk associated with hedging written call options. We introduce a way to isolate the gamma risk from other risk types and present its loss distribution, which has heavy tails. Moving to an insurance point of view, we define a loss ratio that we find to be well behaved with a slightly negative correlation to traditional lines of insurance business, offering diversification opportunities. The tails of the loss distribution are shown to be much fatter than those of the underlying stock returns. We also show that badly estimated volatility, in the Black-Scholes model, leads to considerably biased values for the replicating portfolio. Operational risk is defined as caused by imperfect delta hedging and is found to be limited in today's markets where the autocorrelation of stock returns is small.

The fortune and the risk of a business venture depends on the future course of the economy. There is a strong demand for economic forecasts and scenarios that can be applied to planning and modeling. While there is an ongoing debate on modeling economic scenarios, the bootstrapping (or resampling) approach presented here has several advantages. As a non-parametric method, it directly relies on past market behaviors rather than debatable assumptions on models and parameters. Simultaneous dependencies between economic variables are automatically captured. Some aspects of the bootstrapping method require additional modeling: choice and ransformation of the economic variables, arbitrage-free consistency, heavy tails of distributions, serial dependence, trends and mean reversion. Results of a complete economic scenario generator are presented, tested and discussed.

Die vorliegende Arbeit geht der Frage nach, inwiefern Einstellungen und Verhaltensweisen der Frauen zu Familienplanung und Geburtenregelung auch zwischen den Wohnbezirken einer Stadt unterschiedlich sind, welche Ursachen dafür vorliegen und ob infolgedessen eine regionale Differenzierung bei der medizinischen Betreuung und der sozialen Beratung und Unterstützung erforderlich ist. Mit 3000 zufällig ausgewählten Probandinnen wurden rund 1 % der Ostberliner Frauen im Alter von 15 bis unter 45 Jahren in die Untersuchung einbezogen. Bei der Prüfung der Abhängigkeit der Familienplanung und des Kinderwunsches von der vorliegenden sozioökonomischen Situation der Frauen beziehungsweise der Paare wurde eine jeweilige Regionalanalyse erstellt. Um die soziale Situation der Frau darzustellen, wurden Indikatoren wie Alter der Frau, Anzahl der geborenen Kinder, Familienstand, Bildungsgrad und Erwerbstätigkeit der Frau einbezogen. Entsprechend der regionalen Gliederung Ostberlins in 11 (Stadt-) Bezirke wurde untersucht, ob und in welcher Weise sich die Auffassungen, Meinungen und Verhaltensweisen der dort lebenden Frauen hinsichtlich der von ihnen gewünschten Kinderzahl, der Argumente für einen fehlenden (aktuellen) Kinderwunsch, der Kenntnis, Einstellung und praktizierten Kontrazeption, vorangegangener Schwangerschaftsabbrüche und der Meinung zum Abbruch sowie zum Beginn und der Häufigkeit sexueller Kontakte unterscheiden. Auffallend ist der hohe Anteil junger Frauen mit einer hohen Frequenz sexueller Kontakte, allerdings ohne eine Schwangerschaft anzustreben. Der größte Teil der Verhütung wird durch die Frauen abgedeckt. Dies gilt ebenfalls für den Umgang mit nicht gewollten Schwangerschaften bis hin zur Durchführung einer Abruptio. In der vorliegenden Studie gab knapp ein Drittel der Frauen bereits durchgeführte Schwangerschaftsabbrüche an. Dieses Abbruchverhalten korreliert mit einer oft sehr späten Information über kontrazeptive Möglichkeiten sowie deren Anwendung und muss Grund genug sein, das Wissen um eine gezielte Geburtenregulierung zu intensivieren und je nach regionalen Bedürfnissen umzusetzen. Bei fast allen diesen inhaltlichen Bereichen sind Unterschiede nach dem Wohnsitz der Frau zu erkennen, die mit einem Signifikanzniveau von 5 % Irrtumswahrscheinlichkeit statistisch gesichert werden konnten. Damit konnte die Grundhypothese, dass auch innerhalb einer großstädtischen Population regionale Unterschiede im generativen Verhalten bei Frauen und Paaren bestehen, bestätigt werden. Die regionalen Unterschiede im generativen Verhalten sind vorrangig auf die in den einzelnen Bezirken vorhandenen Sozialstrukturen der Frauen im gebährfähigen Alter zurück-zuführen., The present paper describes the differences that exist in behaviours and attitudes towards family planning and birth control of women from different districts of a big city, the causes of such differences and the resulting need for regional differentiation in health care and social services. The test persons were selected at random. They included 3000 women of age 15 to under 45, ie about 1 % of East Berlin s women of this age bracket. The investigation into the relationship between family planning and wish for children on the one hand and the socio-economic situation of the women (or couples) on the other included a regional analysis. The indicators to describe the social situation of a woman included such data as the age of the woman, the number of children born, her marital status and her gainful employment. An analysis was made on how the women s views, opinions and behaviours regarding desired number of children, the points for not wanting a child at the current time, their knowledge of, attitude toward and practice of contraceptive means, the incidence of previous interruptions of pregnancy and the opinions on abortion as well as on the beginning and frequency of sexual intercourse varied between the 11 municipal districts. The striking thing was that a great proportion of the young women had a high frequency of sexual contacts, but no desire to become pregnant. In most cases the contraceptive measures were covered by the women. This applied also to the handling of unwanted pregnancies, including abortions. Nearly one third of the test persons stated that they had had induced abortions. There was a correlation between abortion behaviour and the age at which information on contraceptive options and their application had been obtained. This should be a good point for intensifying the education on birth control, taking regional requirements and particularities into account. The results of nearly all subjects analysed varied from district to district. With an error probability of only 5 %, these differences can be considered as statistically significant. This confirms one basic hypothesis, namely that the population of a big city shows regional differences in the generative behaviour of women and couples. These regional differences are mainly due to the fact that the social structures that exist for the women capable of childbearing are different in the various districts of the city.

'Implizite Theorien sind schematische Wissenstrukturen über die Stabilität oder die Veränderbarkeit von Merkmalen (Ross 1989). Diese Theorien haben die Funktion, Gedächtnislücken zu füllen, wenn eine genaue Erinnerung nicht möglich ist. Wenn sie jedoch nicht mit der Realität übereinstimmen, führen implizite Theorien zu systematischen Erinnerungsverzerrungen. Es wurde davon ausgegangen, daß Patienten nach einer Operation einen monotonen Genesungsverlauf im Hinblick auf Schmerzen und Schlaf erwarten, und daß diese implizite Theorie die Erinnerung beeinflußt. Sechzig Patienten wurden an fünf aufeinanderfolgenden Tagen im Anschluß an eine orthopädische Operation nach ihren Schmerzen und dem Schlaf der letzten Nacht befragt: am fünften Tag sollten sie sich an ihre Antworten der vergangenen vier Tage erinnern. Es traten systematische Erinnerungsverzerrungen auf. Der Befindlichkeits zustand des ersten Tages wurde in der Erinnerung unterschätzt. In der Erinnerung gab es mehr monotone Verläufe als im täglichen Bericht, Rückfälle im Genesungsprozeß wurden systematisch vergessen. Korrekte implizite Theorien können aber auch zuverlässig Erinnerungslücken schließen. Personen mit monotonen Genesungsverläufen zeigten eine bessere Erinnerungsleistung als Personen, in deren Genesungsverlauf Rückfälle aufgetreten waren.' (Autorenreferat) 'Implicit theories are defined as schematic structures of knowledge about the stability or change of characteristics (Ross 1989). These theories can be used to fill in gaps in recall when memory fails. However, if an implicit theory is incorrect, it may lead to a systematic bias in recall. We hypothesized that patients expect a linear improvement in pain and sleep after an operation so that this implicit theory influences subsequent recall of pain and sleep quality. Sixty surgical patients were asked to rate their pain intensity and sleep quality on each of the 5 days following their operation. On day 5 they were also asked to recall their previous ratings. The recall errors we observed were systematic: The recalled health status of the first post-operative day was worse than the actual reported status. Improvement was recalled more often monotonously than actually reported. Setbacks and relapses in recovery over the the 5-day period tended to be systematically forgotten. On the other hand, correct implicit theories can help to fill recall gaps. Our results suggest that patients whose condition improves linearly post-operatively recalled their ratings more accurately than patients with non-linear patterns of recovery.' (author's abstract)

Die vorliegende Untersuchung basiert auf einer Befragung von insgesamt 12503 Personen in Österreich, Westdeutschland, Irland, Italien, den Niederlanden, Norwegen, Ostdeutschland, Ungarn, Polen und Slowenien. Gefragt wurde nach Religionszugehörigkeit, religiösen Überzeugungen, Religiosität und Wertorientierung. Die Untersuchung zeigt, daß religiöse Überzeugungen im Osten weniger verbreitet sind als im Westen. Protestantisch geprägte Gesellschaften sind anfälliger gegen Säkularisierungstendenzen als katholische Gesellschaften. Sogar bei Kirchenmitgliedern ist der Einfluß religiöser Überzeugungen auf ethische Einstellungen begrenzt. Ungläubige Personen sind nicht unbedingt areligiös. (ICE)

C6H14N3NaO8S, monoclinic, P121/c1 (no. 14), a = 7.018(1) Å, b = 27.193(5) Å, c = 7.089(1) Å, β = 92.01(2)°, V = 1352.0 Å3, Z = 4, Rgt(F) = 0.071, wRref(F2) = 0.160, T = 193 K.