Three-body nature of N(*) and Δ(*) resonances from sequential decay chains.

The Nπ^{0}π^{0} decays of positive-parity N^{*} and Δ^{*} resonances at about 2 GeV are studied at ELSA by photoproduction of two neutral pions off protons. The data reveal clear evidence for several intermediate resonances: Δ(1232), N(1520)3/2^{-}, and N(1680)5/2^{+}, with spin parities J^{P}=3/2^{+}, 3/2^{-}, and 5/2^{+}. The partial wave analysis (within the Bonn-Gatchina approach) identifies N(1440)1/2^{+} and the N(ππ)_{S wave} (abbreviated as Nσ here) as further isobars and assigns the final states to the formation of nucleon and Δ resonances and to nonresonant contributions. We observe the known Δ(1232)π decays of Δ(1910)1/2^{+}, Δ(1920)3/2^{+}, Δ(1905)5/2^{+}, Δ(1950)7/2^{+}, and of the corresponding spin-parity series in the nucleon sector, N(1880)1/2^{+}, N(1900)3/2^{+}, N(2000)5/2^{+}, and N(1990)7/2^{+}. For the nucleon resonances, these decay modes are reported here for the first time. Further new decay modes proceed via N(1440)1/2^{+}π, N(1520)3/2^{-}π, N(1680)5/2^{+}π, and Nσ. The latter decay modes are observed in the decay of N^{*} resonances and at most weakly in Δ^{*} decays. It is argued that these decay modes provide evidence for a 3-quark nature of N^{*} resonances rather than a quark-diquark structure.

Background paper to the recommendation for the preferential use of live-attenuated influenza vaccine in children aged 2-6 years in Germany.

The German Standing Committee on Vaccination (STIKO) recommends seasonal influenza vaccination for children and adolescents with chronic medical conditions that put them at risk for severe influenza illness. In addition to trivalent inactivated influenza vaccines (TIV), a trivalent live-attenuated influenza vaccine (LAIV) was licensed for children and adolescents aged 2-17 years in the European Union in 2011. Employing the methodology of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group, we examined the evidence for efficacy and safety of LAIV relative to TIV to guide STIKO's decision on whether LAIV should be preferentially recommended for at-risk children. In our meta-analysis of data from two randomized trials directly comparing LAIV and TIV in children aged ≤ 6 years, the protective efficacy of LAIV against laboratory-confirmed influenza was 53 % [95 % confidence interval (CI): 45-61 %] higher than that of TIV. A similar study in individuals aged 6-17 years showed a 32 % (95 % CI: 3-52 %) higher efficacy of LAIV. The quality of the evidence for a superior protective efficacy of LAIV against all relevant clinical outcomes was rated 'moderate' for children aged 2-6 years and 'low' for the age group 7-17 years. Regarding safety outcomes, the available data suggest no significant differences between LAIV and TIV. Based on these results, STIKO recommends that LAIV should be used preferentially for influenza vaccination of at-risk children aged 2-6 years. In children and adolescents aged 7-17 years, either LAIV or TIV may be used without specific preference. Possible contraindications and the vaccinee's and his/her guardians' preferences should be taken into account.

Background paper to the recommendation for routine rotavirus vaccination of infants in Germany.

Two rotavirus (RV) vaccines were introduced to the European market in 2006. To support the decision-making process of the German Standing Committee on Vaccination ("Ständige Impfkommission", STIKO) regarding adoption of routine RV vaccination into the national vaccination schedule in Germany relevant scientific background was reviewed. According to STIKO's Standard Operating Procedures for the development of evidence-based vaccination recommendations, a set of key questions was addressed and systematic reviews were performed with a focus on the efficacy, effectiveness, impact and safety of RV vaccines. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was applied to assess the quality of available evidence. Data from 5 randomized controlled trials demonstrated a high efficacy of RV vaccines in preventing severe RV-associated gastroenteritis (91%) and hospitalization (92%) in settings comparable to Germany. Post-marketing observational studies confirmed these findings. In several countries, impact studies suggest that age groups not eligible for vaccination might also benefit from herd effects and demonstrated a decrease in the number of nosocomial RV infections after RV vaccine introduction. The vaccines were considered safe, except for a slightly increased risk of intussusception shortly after the first dose, corresponding to 1-2 additional cases per 100,000 infants vaccinated (relative risk =1.21, 95% confidence interval [CI] 0.68-2.14). RV case-fatality is extremely low in Germany. However, RV incidence among children aged <5 years is high (reported 8-14 cases per 1000 children annually), and of these almost half require hositalization. In view of the available evidence and expected benefits, STIKO recommends routine rotavirus vaccination of children under the age of 6 months with the main goal of preventing RV-associated hospitalizations in Germany, especially among infants and young children.

[Concepts, effectiveness, and perspectives of pandemic and seasonal influenza vaccines]. / Konzepte, Wirksamkeit und Perspektiven pandemischer und nichtpandemischer Influenzaimpfungen.

For the first time in history, the conditions to influence the course of an influenza pandemic through vaccination were set during the influenza A H1N1 pandemic in 2009. The specific requirements for pandemic vaccines are to be highly immunogenic in immunologically naive individuals and to be producible quickly in large quantities. In contrast, seasonal influenza vaccines induce a booster response and a broadening of preexisting immunity. In this article the concepts of seasonal and pandemic influenza vaccines and data on their immunogenicity and clinical efficacy are reviewed and discussed. In the upcoming years, seasonal influenza vaccination will continue to be based on inactivated split-virion and subunit vaccines or the live attenuated cold-adapted vaccine. The pandemic vaccines used in 2009 proved to be more immunogenic than expected from prepandemic vaccine trials, while the adverse events observed with AS03-adjuvanted vaccines call their future use into question. However, neither seasonal nor pandemic influenza vaccines can be regarded to be an ideal solution, because they have to be frequently adapted to new virus strains and they lack effectiveness in particular risk groups. They can be regarded as interim approaches to highly immunogenic vaccines that hopefully become available in the future. The underlying principles of future vaccines are also presented in this article.

[Prevention of nosocomial transmission of human immunodeficiency virus (HIV) from HIV-positive healthcare workers. Recommendations of the German Association for the Control of Viral Diseases (DVV) e.V. and the Society for Virology (GfV) e.V]. / Prävention der nosokomialen Übertragung von humanem Immunschwächevirus (HIV) durch HIV-positive Mitarbeiterinnen und Mitarbeiter im Gesundheitswesen. Empfehlungen der Deutschen Vereinigung zur Bekämpfung der Viruskrankheiten (DVV) e.V. und der Gesellschaft für Virologie (GfV) e.V.

To the best of our knowledge, the German Association for the Control of Viral Diseases (DVV) e.V. and the Society for Virology (GfV) e.V. are the first in Europe to provide precise recommendations for the management of health care workers (HCWs) who are infected with human immunodeficiency virus (HIV). Requirements for HIV-infected HCWs need to be clearly defined. With a permanent viral burden of less than or equal to 50 copies/mL, HIV-positive HCWs are allowed to perform any surgery and any invasive procedure, as long as the infected HCW uses double-gloving, undergoes follow-up routinely by occupational medicine professionals, undergoes a quarterly examination of viral burden, and has a regular medical examination by a physician who has expertise in the management of HIV. Unrestricted professional activity is only possible with a strict compliance to take antiretroviral therapy and if the HIV-infected HCW strictly adheres to the recommended infection control procedures. Complete compliance with the recommendation almost certainly leads to no HIV transmission risk in patient care.

Influenza A(H1N1)pdm09 antibodies after pandemic and trivalent seasonal influenza vaccination as well as natural infection in November 2010 in Hamburg, Germany.

The 2009 influenza pandemic has introduced the new re-assorted influenza A(H1N1)pdm09 virus which recirculated during the 2010/11 influenza season. Before that season, it was possible to acquire protective immunity either by pandemic or seasonal influenza vaccination against influenza A(H1N1)pdm09 or by natural infection. To obtain data on vaccination coverage and antibody levels in a reference population and to calculate whether or not the herd immunity threshold (HIT, calculated as 33% given an R0 of 1.5) was reached at the beginning of the 2010/11 season we performed a seroprevalence study in November 2010 in Hamburg, Germany. Antibody titres were assessed applying a haemagglutination inhibition test. Vaccination coverage was very low: 14% for pandemic and 11% for seasonal 2010/11 vaccinations. Even in those with underlying risk factors, vaccination coverage was not much higher: 17% for both vaccines. Serological analysis revealed antibody titres of ≥1:10 in 135 of 352 (38%) and of ≥1:40 in 61 of 352 study participants (17%). Specific antibodies were measurable in 26% of those without history of vaccination or natural infection, indicating a high proportion of subclinical and mild influenza disease. Nevertheless, the HIT was not reached, leaving the majority of the population susceptible to influenza A(H1N1)pdm09 and its potential complications.

[The spinoglenoid ligament - an anatomic study]. / Das spinoglenoidale Ligament - eine anatomische Studie.

PURPOSE: In over-head motion athletes a dysfunction of the suprascapular nerve has been described. In the literature a relation between the spinoglenoid ligament and the dysfunction of the suprascapular nerve is mentioned. An appreciable variability of this ligament is described. The purpose of the present study was the anatomic documentation of the spinoglenoid ligament and its relation to the suprascapular nerve. MATERIAL AND METHODS: In 36 shoulder specimen the suprascapular nerve, the spinoglenoid and bony parameter of the scapula were documented. The statistic evaluation was performed with SPSS12.0. RESULTS: In all but one specimen a spinoglenoid ligament was present. In 20 cases (56 %) the infraspinatus muscle inserted at the spinoglenoid ligament. In five cases (14 %) the spinoglenoid ligament reached the glenohumeral joint capsule. In two cases the suprascapular nerve was completely fixed with the ligament, in four cases the perineural soft tissue had a close connection to the ligament. In four cases a branch of the nerve passed through the ligament. All together in 28 % of the specimen there were mechanical conflicts. In one case a ganglion compressed the nerve. CLINICAL RELEVANCE: Our anatomic study showed in a significant number of cases a possible entrapment of different origins. These findings have implications both for diagnostics and treatment.

New measurements of the European Muon Collaboration effect in very light nuclei.

New Jefferson Lab data are presented on the nuclear dependence of the inclusive cross section from (2)H, (3)He, (4)He, (9)Be and (12)C for 0.3 < x < 0.9, Q(2) approximately 3-6 GeV(2). These data represent the first measurement of the EMC effect for (3)He at large x and a significant improvement for (4)He. The data do not support previous A-dependent or density-dependent fits to the EMC effect and suggest that the nuclear dependence of the quark distributions may depend on the local nuclear environment.

Quasifree photoproduction of eta mesons off the neutron.

Quasifree photoproduction of eta mesons off nucleons bound in the deuteron has been measured with the CBELSA/TAPS detector for incident photon energies up to 2.5 GeV at the Bonn ELSA accelerator. The eta mesons have been detected in coincidence with recoil protons and recoil neutrons, which allows a detailed comparison of the quasifree n(gamma,eta)n and p(gamma,eta)p reactions. The excitation function for eta production off the neutron shows a pronounced bumplike structure at W=1.68 GeV (E{gamma} approximately 1 GeV), which is absent for the proton.

Modification of the omega-meson lifetime in nuclear matter.

Information on hadron properties in the nuclear medium has been derived from the photoproduction of omega mesons on the nuclei C, Ca, Nb, and Pb using the Crystal Barrel/TAPS detector at the ELSA tagged photon facility in Bonn. The dependence of the omega-meson cross section on the nuclear mass number has been compared with three different types of models: a Glauber analysis, a Boltzmann-Uehling-Uhlenbeck analysis of the Giessen theory group, and a calculation by the Valencia theory group. In all three cases, the inelastic omega width is found to be 130-150 MeV/c(2) at normal nuclear matter density for an average 3-momentum of 1.1 GeV/c. In the rest frame of the omega meson, this inelastic omega width corresponds to a reduction of the omega lifetime by a factor approximately 30. For the first time, the momentum dependent omegaN cross section has been extracted from the experiment and is in the range of 70 mb.

Targeted release of oncolytic measles virus by blood outgrowth endothelial cells in situ inhibits orthotopic gliomas.

Malignant gliomas remain largely incurable despite intensive efforts to develop novel therapies. Replicating oncolytic viruses have shown great promise, among them attenuated measles viruses of the Edmonston B strain (MV-Edm). However, host immune response and the infiltrative nature of gliomas limit their efficacy. We show that human blood outgrowth endothelial cells (BOECs), readily expandable from peripheral blood, are easily infected by MV-Edm and allow replication of MV-Edm while surviving long enough after infection to serve as vehicles for MV-Edm (BOEC/MV-Edm). After intravenous and peritumoral injection, BOEC/MV-Edm deliver the viruses selectively to irradiated orthotopic U87 gliomas in mice. At the tumor, MV-Edm produced by the BOECs infect glioma cells. Subsequent spread from tumor cell to tumor cell leads to focal infection and cytopathic effects that decrease tumor size and, in the case of peritumoral injection, prolong survival of mice. Since MV-Edm within BOECs are not readily neutralized and because BOEC/MV-Edm search and destroy glioma cells, BOEC/MV-Edm constitute a promising novel approach for glioma therapy.

CMV monitoring using blood cells and plasma: a comparison of apples with oranges?

Quantitative cytomegalovirus (CMV) monitoring is still far from being standardized between transplant centers. In the present study, we compared assays for quantitative CMV monitoring using blood cells and plasma. Four hundred and thirty-five consecutive samples from 29 patients with active CMV infection after allogeneic T-cell-depleted hemopoietic stem cell transplantation were tested in parallel using pp65 antigenemia and quantitative CMV polymerase chain reaction (PCR) in blood cells and plasma (COBAS AMPLICOR CMV MONITOR). Although only 142 (53.1%) of 253 positive samples were concordantly identified by all three assays, the number of positive samples detected by each assay was not different and the quantitative values were correlated, provided that nucleic acid (NA) in plasma was isolated by COBAS AmpliPrep and not by the manual protocol. Six (18%) of 34 episodes with active CMV infection were not detected using CMV PCR in plasma; whereas in times of white blood cell aplasia or blast crisis of leukemia, samples with active CMV infection in plasma could not be detected using blood cells. We conclude that CMV monitoring in whole blood could be favorable compared with assays using plasma or blood cells alone. Automated NA isolation could become an attractive tool for a more sensitive and better standardized molecular diagnostics.

Measurement of nuclear transparency for the A(e,e'pi+) reaction.

We have measured the nuclear transparency of the A(e,e'pi+) process in 2H, 12C, 27Al, 63Cu, and 197Au targets. These measurements were performed at the Jefferson Laboratory over a four momentum transfer squared range Q2=1.1 to 4.7 (GeV/c)2. The nuclear transparency was extracted as the super-ratio of (sigmaA/sigmaH) from data to a model of pion-electroproduction from nuclei without pi-N final-state interactions. The Q2 and atomic number dependence of the nuclear transparency both show deviations from traditional nuclear physics expectations and are consistent with calculations that include the quantum chromodynamical phenomenon of color transparency.

Observation of in-medium modifications of the omega meson.

The photoproduction of omega mesons on nuclei has been investigated using the Crystal Barrel/TAPS experiment at the ELSA tagged photon facility in Bonn. The aim is to study possible in-medium modifications of the omega meson via the reaction gamma + A --> omega + X --> pi(0)gamma + X('). Results obtained for Nb are compared to a reference measurement on a LH2 target. While for recoiling, long-lived mesons (pi(0), eta, and eta;(')), which decay outside of the nucleus, a difference in the line shape for the two data samples is not observed, we find a significant enhancement towards lower masses for omega mesons produced on the Nb target. For momenta less than 500 MeV/c an in-medium omega meson mass of M(medium) = [722(+4)(-4)(stat)+35-5(syst)] MeV/c(2) has been deduced at an estimated average nuclear density of 0.6rho(0).

[ Update 2001. Myocarditis--cardiomyopathy]. / Update 2001. Myokarditis--Kardiomyopathie.

Myocarditis is a common cardiological disease. New molecular biological and immunohistological methods have confirmed the persistence of viral infection and chronic myocardial inflammation in a considerable number of patients. A causal link between viral myocarditis and the development of dilated cardiomyopathy has been recognized. This has prognostic implications and helps for the decision of a specific immunosuppressive, immunomodulatory and antiviral therapy.

Fatal outcome in a patient developing Epstein-Barr virus-associated lymphoproliferative disorder (EBV-LPD) without measurable disease.

A 51-year-old female patient in the first chronic phase of CML received an allogeneic PBSCT from a matched unrelated donor. The transplant was manipulated by CD34+ cell selection. On day +193 after transplantation the patient was readmitted to the hospital with recurrent fever of unknown origin and cough. Clinical, radiographic and sonographic evaluation revealed no characteristic findings besides a mild splenomegaly. Screening for EBV, CMV, RSV and HSV did not indicate an active infection. On day +203 the patient developed generalized seizures, respiratory failure and died within 24 h in multiorgan failure. The macroscopic postmortem was still not enlightening; the histological examination however, demonstrated diffuse organ infiltration by monoclonal lymphoblastoid cells due to EBV-LPD.

Use of dyes to investigate migration of the chiral selector in CFFE and the impact on the chiral separations.

Continuous free flow electrophoresis was investigated as a tool for the preparative chiral separation of piperoxan enantiomers using sulfated beta-cyclodextrin (sbeta-CD) as the chiral additive. Bulk migration of sbeta-CD was confirmed using LC-MS analysis of the individual fractions collected and visualized with the addition of crystal violet to the separation buffer. In the absence of sbeta-CD, the crystal violet-containing buffer was reddish/purple and the crystal violet was deflected cathodically in the chamber. In the presence of sbeta-CD, the crystal violet-containing buffer was blue and was deflected anodically. However, formation of accumulation and depletion zones was apparent in both cases. The addition of sbeta-CD to the cathodic wash solution allowed for almost complete resolution of the piperoxan enantiomers with a processing rate of 0.45 mg/ h.

Aciclovir selects for ganciclovir-cross-resistance of human cytomegalovirus in vitro that is only in part explained by known mutations in the UL97 protein.

Phenotypically, ganciclovir-resistant human cytomegalovirus strains could be selected by aciclovir as effectively as by ganciclovir in vitro. Three clinical human cytomegalovirus isolates with different sensitivities against ganciclovir, aciclovir, foscarnet, and cidofovir, but without any mutation in the viral UL97 protein known to confer ganciclovir resistance, were propagated each in duplicate in the presence of ganciclovir or aciclovir. After drug selection, all 12 strains were less susceptible to ganciclovir (increase of 50% focus reduction dose between 2.1- and 31.5-fold) but were still sensitive to foscarnet and cidofovir; 7/12 exhibited a ganciclovir-resistant phenotype with a 50% focus reduction dose >30 microM, and in 6 out of these typical mutations in the UL97 coding region could be found by genotyping. All four strains selected from one isolate carried the identical UL97 mutation at amino acid position 460 (methionine to valine). The decreased sensitivity to ganciclovir and aciclovir in the other strains could neither be attributed to known UL97 mutations nor to mutations in the viral polymerase (UL54), which have been reported to induce resistance.

Indolocarbazoles exhibit strong antiviral activity against human cytomegalovirus and are potent inhibitors of the pUL97 protein kinase.

We have analyzed a panel of protein kinase inhibitors (PKIs) and found that some indolocarbazoles (Gö6976, K252a, K252c) proved to be highly effective inhibitors of GCV-sensitive and -resistant human cytomegalovirus (HCMV) strains, but did not show any effect against herpes simplex virus. Antiviral activity was determined by focus reduction assays (IC(50) ranging from 0.009 to 0.4 microM). Other inhibitors of serine/threonine kinases (Gö6850, H-7, roscovitine) were found to be ineffective. Virus yield at 5 days after infection was reduced by three orders of magnitude with nanomolar concentrations of the indolocarbazoles. These compounds were fully effective when added up to 24 h post infection and showed reduced activity up to 72 h post infection. Cytotoxicity assays in proliferating and non-proliferating cells demonstrated that the effective antiviral concentration of these compounds was significantly lower than either antiproliferative (IC(50)/CC(50) ranging from 6.5 to 390) or cytotoxic (IC(50)/CC(50) ranging from 72. 5 to 1000) doses. The effects of PKIs on the virus-encoded protein kinase pUL97 were studied using recombinant vaccinia viruses. Indolocarbazoles strongly inhibited both pUL97 autophosphorylation (IC(50) ranging from 0.0012 to 0.013 microM) and pUL97-dependent ganciclovir phosphorylation (IC(50) ranging from 0.05 to 0.26 microM). Other inhibitors of serine/threonine kinases showed only weak (Gö6850) or no (H-7, roscovitine) effect on these pUL97 functions, while oxoflavone tyrosine kinase inhibitors had no effect at all.