Versatile optical laser system for experiments at the European X-ray free-electron laser facility.

We present the main features of the final prototype of a pulsed optical laser, developed for pump-probe and other experiments in conjunction with the femtosecond x-ray beams at the European X-ray free-electron laser facility. Adapted to the temporal x-ray emission pattern of the facility, the laser provides 10 Hz bursts of up to 600 µs duration with intra-burst pulse frequencies as high as 4.5 MHz. In this mode, we have generated pulses as short as 12 fs at 350 W average power during the burst and with beam qualities close to the diffraction limit. This is, to the best of our knowledge, the highest power to date of a few-cycle laser operating at a center wavelength of 800 nm. Important for experimental flexibility, the laser can be configured in various unique ways, enabling, e.g., energy scaling to >3 mJ per pulse through a frequency change down to 100 kHz and the generation of nearly transform limited pulses between 12 fs and 300 fs. In addition to the 800 nm femtosecond beam line, a synchronized long pulse (0.8 ps or 400 ps) 1030 nm beam can be utilized, offering up to 4 kW burst average power, i.e. up to 40 mJ per pulse at 100 kHz. Efficient nonlinear wavelength conversion and tuning through intrinsic and external means further enhance the capabilities of the laser.

Femtosecond all-optical synchronization of an X-ray free-electron laser.

Many advanced applications of X-ray free-electron lasers require pulse durations and time resolutions of only a few femtoseconds. To generate these pulses and to apply them in time-resolved experiments, synchronization techniques that can simultaneously lock all independent components, including all accelerator modules and all external optical lasers, to better than the delivered free-electron laser pulse duration, are needed. Here we achieve all-optical synchronization at the soft X-ray free-electron laser FLASH and demonstrate facility-wide timing to better than 30 fs r.m.s. for 90 fs X-ray photon pulses. Crucially, our analysis indicates that the performance of this optical synchronization is limited primarily by the free-electron laser pulse duration, and should naturally scale to the sub-10 femtosecond level with shorter X-ray pulses.

High power burst-mode optical parametric amplifier with arbitrary pulse selection.

We present results from a unique burst-mode femtosecond non-collinear optical parametric amplifier (NOPA) under development for the optical - x-ray pump-probe experiments at the European X-Ray Free-Electron Laser Facility. The NOPA operates at a burst rate of 10 Hz, a duty cycle of 2.5% and an intra-burst repetition rate of up to 4.5 MHz, producing high fidelity 15 fs pulses at a center wavelength of 810 nm. Using dispersive amplification filtering of the super-continuum seed pulses allows for selectable pulse duration up to 75 fs, combined with a tuning range in excess of 100 nm whilst remaining nearly transform limited. At an intra-burst rate of 188 kHz the single pulse energy from two sequential NOPA stages reached 180 µJ, corresponding to an average power of 34W during the burst. Acousto- and electro-optic switching techniques enable the generation of transient free bursts of required length and the selection of arbitrary pulse sequences inside the burst.

Single-shot pulse duration monitor for extreme ultraviolet and X-ray free-electron lasers.

The resolution of ultrafast studies performed at extreme ultraviolet and X-ray free-electron lasers is still limited by shot-to-shot variations of the temporal pulse characteristics. Here we show a versatile single-shot temporal diagnostic tool that allows the determination of the extreme ultraviolet pulse duration and the relative arrival time with respect to an external pump-probe laser pulse. This method is based on time-resolved optical probing of the transient reflectivity change due to linear absorption of the extreme ultraviolet pulse within a solid material. In this work, we present measurements performed at the FLASH free-electron laser. We determine the pulse duration at two distinct wavelengths, yielding (184±14) fs at 41.5 nm and (21±19) fs at 5.5 nm. Furthermore, we demonstrate the feasibility to operate the tool as an online diagnostic by using a 20-nm-thin Si3N4 membrane as target. Our results are supported by detailed numerical and analytical investigations.

Compact picosecond mode-locked and cavity-dumped Nd:YVO4 laser.

We report on a diode pumped, semiconductor saturable absorber mirror mode-locked picosecond Nd:YVO(4) oscillator with cavity-dumping. In pure cw-mode-locking this laser produced up to 17W of average power at a pulse repetition rate of 9.7MHz, corresponding to a pulse energy of 1.7microJ. Using an electro-optic cavity dumper, we achieved average powers up to 7.8W at 500kHz and 10W at 1MHz dumping rate. With corresponding pulse energies of 15.6microJ and 10microJ respectively and pulsewidths around 10ps, this laser could become a compact source for materials processing applications, alternative to more complex schemes such as regenerative amplifiers or ultra-long resonator oscillators.

Molecular and clinical characteristics of respiratory syncytial virus infections in hospitalized children.

The objective of this study was to determine the importance of respiratory syncytial virus (RSV) for hospitalization in the north east of Germany and to obtain molecular epidemiological data of the circulating strains. Using a rapid and sensitive reverse transcriptase-PCR, it was found that a quarter of pediatric respiratory disease admissions were due to RSV. Infections caused by RSV in hospitalized patients were determined over the whole year. Both RSV groups A and B were identified with a predominance of RSV A (86%) over the entire period. The analysis of the deduced amino acid sequences by direct sequencing showed that very similar RSV strains are circulating in the community.

Are enterovirus infections a co-factor in sudden hearing loss?

Since viral infections are believed to be one of the causes of sudden hearing loss we have used serological assays for herpes simplex virus (HSV), varicella zoster virus (VZV), and enterovirus as well as polymerase chain reaction for enterovirus to test 55 sudden hearing loss patients for viral infections. Serological screening of these patients for HSV and VZV failed to reveal significant differences between the patient group and the controls. In contrast, enterovirus sequences were detected by RT-PCR in 40% of the patient group, but in none of the controls, suggesting that enterovirus infections may be associated with sudden hearing loss.

[Diagnostic shifts of functional psychoses in the transition from ICD-9 to ICD-10]. / Diagnoseverschiebungen der funktionellen Psychosen beim Ubergang von der ICD-9 zur ICD-10.

In order to identify diagnostic changes caused by the transition from ICD-9 to ICD-10, in a sample of 218 first hospitalised patients from the years 1980 and 1981, ICD-9 diagnoses were compared with ICD-10 diagnoses. For this comparison, functional psychoses were classified into five main diagnostic groups. Results showed a decreased frequency of the diagnostic groups schizophrenia, schizoaffective psychoses, and paranoid psychoses and an increased frequency of the diagnostic groups acute psychoses and affective psychoses. With the exception of acute psychoses and schizoaffective psychoses, a high agreement between ICD-9 and ICD-10 diagnoses was found, and the Kappa value was 0.70. With regard to the homogeneity of psychopathological symptoms, ICD-10 diagnoses showed no improvement over ICD-9 diagnoses. Nevertheless, ICD-10 diagnoses have gained in predictive validity because schizophrenia was further narrowed to cases with a more unfavourable outcome.

Real-time PCR to improve the diagnosis of respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) is one of the most important virus respiratory pathogens in infants and young children. A rapid and sensitive diagnosis is essential to focus any outbreak due to this virus. A real-time RT-PCR method was designed using a primer/probe pair from the F gene. Simultaneously with nested RT-PCR and antigen ELISA, 71 consecutive specimens from hospitalized children with clinical symptoms of acute respiratory distress were evaluated to confirm the incidence of RSV infection. RSV was detected in 25 (35.2 %) specimens by real-time RT-PCR and in 19 (26.7 %) by nested RT-PCR. The assay was specific for RSV. The procedure offers a rapid and sensitive alternative to conventional RT-PCR. Closed-tube detection eliminates the risk of contamination.

Inhibitory effect of Bergenia ligulata on influenza virus A.

Methanol water extract from rhizomes of Bergenia ligulata, a plant used in Nepalese ethnomedicine, inhibited in vitro the replication of influenza virus in a dose dependent manner and did not show virucidal activity at effective concentration. Pretreatment of cells with B. ligulata extract was shown to be most effective to prevent cell destruction. The extract inhibited viral RNA synthesis and reduced viral peptide synthesis at 10 microg/ml. The virus inhibitory effect is related to the presence of condensed tannins in the extract.

Antiviral lanostanoid triterpenes from the fungus Ganoderma pfeifferi.

Ganodermadiol, lucidadiol and applanoxidic acid G were isolated as first triterpenes from the European Basidiomycete Ganoderma pfeifferi. The compounds show antiviral activity against influenza virus type A and HSV type 1.

Cyanobacteria a potential source of antiviral substances against influenza virus.

Aqueous and methanolic extracts of cultured cyanobacteria of several genera, Microcystis, Nodularia, Oscillatoria, Scytonema, Lyngbya and Calothrix were evaluated for their in vitro antiviral activity against influenza A virus in Madin Darby canine kidney cells. None of the methanolic extracts showed cytotoxic effects. The inhibitory concentration (IC(50)) of antiviral activity ranged between 20.0 micro g to 79.0 micro g extract/ml. The most active extract in this screening derived from genus Microcystis. The further analysis of methanolic extracts of cultured strains of genus Microcystis revealed a remarkable antiviral activity against influenza A virus for M. aeruginosa, M. ichthyoblabe and M. wesenbergii. The observed antiviral activity was associated with protease inhibitory activity of approximately 90% and suggest that protease inhibitory activity may be responsible for reducing virus replication. These results show that cyanobacteria are able to produce compounds with biological activity that may be of potential clinical interest.

Screening of Nepalese medicinal plants for antiviral activity.

In an ethnopharmacological screening, plants used in Nepalese traditional medicine were evaluated for antiviral activity. Methanolic and methanolic-aqueous extracts derived of 23 species were assayed in two in vitro viral systems, influenza virus/MDCK cells and herpes simplex virus/Vero cells. Two species, Bergenia ligulata and Nerium indicum showed the highest antiinfluenzaviral activity with 50% inhibitory dose of 10 microg/ml. Holoptelia integrifolia and N. indicum exhibited considerable antiviral activity against herpes simplex virus. None of these extracts showed cytotoxic effects. Additionally for B. ligulata and H. integrifolia partial protease inhibitory activity was estimated.

Evaluation of the efficacy of 2',3'-dideoxycytidine against adenovirus infection in a mouse pneumonia model.

The antiviral activity of 2',3'-dideoxycytidine (ddC) has been investigated in a mouse pneumonia model. Consolidation of lung, histopathological changes, DNA synthesis as well as levels of TNFalpha were assayed. In this in vivo model, the oral administration of ddC twice daily over 4 days, displayed an inhibitory effect. The drug significantly reduced histopathologic responses. Analysis indicated that under treatment pulmonary lesions were less severe than those of untreated controls. These data confirm the in vitro activity of ddC against adenovirus. Thus, ddC represents a potential therapeutic approach for inhibiting adenovirus infection and may offer promise as an anti-adenovirus agent for immunocompromised patients in whom serious adenovirus infection may prove fatal.

Inhibition of adenovirus DNA polymerase by modified nucleoside triphosphate analogs correlate with their antiviral effects on cellular level.

Adenovirus (Ad) infection results in significant morbidity and mortality in both immunocompetent and immunosuppressed hosts. There is currently no licensed chemotherapy effective in dealing with this virus infection. In this study the anti-adenoviral activity of a group of modified nucleoside analogs was investigated. The most efficient 3-fluorosubstituted nucleoside triphosphate inhibitors of Ad DNA polymerase were 3'-fluorothymidine triphosphate (IC50 0.63 microM), 2',3'-dideoxy-3'-fluoroguanosine triphosphate (IC50 0.71 microM) and 2',3'-dideoxy-3'-fluorouridine triphosphate (IC50 2.96 microM). The most efficient 2',3'-dideoxynucleoside triphosphates were 2',3'-dideoxycytidine triphosphate (ddCTP; IC50 1.0 microM), 2',3'-dideoxyadenosine triphosphate (IC50 1.6 microM) and 2',3'-dideoxythymidine triphosphate (IC50 1.82 microM). Kinetic studies indicate competitive inhibition of adenovirus DNA polymerase by ddCTP. These data confirm results previously obtained at the cellular level using a focus reduction assay involving Ad2-infected FL cells. Whereas the D-enantiomers 3'-fluorothymidine and 2',3'-dideoxycytidine are potent inhibitors of adenoviral replication, the corresponding L-enantiomers exhibited no inhibitory activity.

Long-term course of schizophrenic, affective and schizoaffective psychosis: focus on negative symptoms and their impact on global indicators of outcome.

OBJECTIVE: The aim of this study was to compare indicators of outcome between different types of psychosis and to verify whether or not negative symptoms (NS) have a special relevance for schizophrenia. METHOD: This is a follow-up study on functional psychosis according to ICD-9. Patients were assessed standardized at the time of first hospitalization and about 12.5 years later. RESULTS: Comparison of global outcome parameters and NS revealed that schizophrenia had the poorest outcome of all types of psychosis. NS had the highest impact on global functioning and the severity of illness in schizophrenia. NS assessed at the first hospitalization were associated with the different outcome parameters only in schizophrenia at follow-up. CONCLUSION: The course of schizophrenia is a more deteriorating one than that of affective or schizoaffective psychosis. The findings point to the special relevance of NS for the outcome and their relative specificity for schizophrenia.

[Psychiatric side effects during adjuvant therapy with interferon-alphain patients with malignant melanoma. Clinical evaluation as well as diagnostic and therapeutic possibilities]. / Psychiatrische Nebenwirkungen während adjuvanter Therapien mit Interferon-alpha bei Patienten mit malignen Melanomen. Klinische Einschätzun sowie diagnostiche und therapeutische Möglichkeiten.

Interferon-alpha (IFN-alpha) is of high interest in the adjuvant treatment of malignant melanoma. During long term treatment, psychiatric side effects play an important role and not infrequently lead to reduction or discontinuation of therapy. Most common are sleeping disturbance, agitation, weariness, sleepiness, irritability, social withdrawal and depression, which most often develop during the first three months of the therapy. Also more severe side effects may occur, like delirium, organic depression, psychotic episodes and organic personality change, which in some patients may even lead to suicidal thoughts or suicide attempts, which is illustrated in two case reports. Therapeutic intervention depend to the severity of side effects. Moderate depressive syndromes may successfully be treated by antidepressive drugs like serotonin reuptake inhibitors (SSRI), which may even allow continuation of IFN-alpha therapy. In patients with severe depression or organic personality changes with increased risk of suicide, immideate discontinuation of IFN-alpha therapy is mandatory and treatment in a psychiatric hospital must be considered.

[Dysmorphophobia--symptom or diagnosis?]. / Dysmorphophobie--Symptom oder Diagnose?

Dysmorphophobia as a new psychiatric syndrome was described by the Italian psychiatrist Morselli in 1891. Dysmorphophobic symptoms are associated with several other psychiatric disorders. The term of dysmorphophobia will be discussed along a theoretical review. We present the case of a 20-year-old patient with dysmorphophobic symptoms. In the scope of ICD 10, DSM-III-R/DSM IV diagnostical criteria we outline problems of the diagnostical classification of dysmorphophobic signs.