The group-based social skills training SOSTA-FRA in children and adolescents with high functioning autism spectrum disorder - study protocol of the randomised, multi-centre controlled SOSTA - net trial

Background: Group-based social skills training (SST) has repeatedly been recommended as treatment of choice in high-functioning autism spectrum disorder (HFASD). To date, no sufficiently powered randomised controlled trial has been performed to establish efficacy and safety of SST in children and adolescents with HFASD. In this randomised, multi-centre, controlled trial with 220 children and adolescents with HFASD it is hypothesized, that add-on group-based SST using the 12 weeks manualised SOSTA–FRA program will result in improved social responsiveness (measured by the parent rated social responsiveness scale, SRS) compared to treatment as usual (TAU). It is further expected, that parent and self reported anxiety and depressive symptoms will decline and pro-social behaviour will increase in the treatment group. A neurophysiological study in the Frankfurt HFASD subgroup will be performed pre- and post treatment to assess changes in neural function induced by SST versus TAU. Methods/design: The SOSTA – net trial is designed as a prospective, randomised, multi-centre, controlled trial with two parallel groups. The primary outcome is change in SRS score directly after the intervention and at 3 months follow-up. Several secondary outcome measures are also obtained. The target sample consists of 220 individuals with ASD, included at the six study centres. Discussion: This study is currently one of the largest trials on SST in children and adolescents with HFASD worldwide. Compared to recent randomised controlled studies, our study shows several advantages with regard to in- and exclusion criteria, study methods, and the therapeutic approach chosen, which can be easily implemented in non-university-based clinical settings. Trial registration: ISRCTN94863788 – SOSTA – net: Group-based social skills training in children and adolescents with high functioning autism spectrum disorder

V2:Performance of the solid deuterium ultra-cold neutron source at the pulsed reactor TRIGA Mainz

The performance of the solid deuterium ultra-cold neutron source at the pulsed reactor TRIGA Mainz with a maximum peak energy of 10 MJ is described. The solid deuterium converter with a volume of V=160 cm3 (8 mol), which is exposed to a thermal neutron fluence of 4.5x10^13 n/cm2, delivers up to 550 000 UCN per pulse outside of the biological shield at the experimental area. UCN densities of ~ 10/cm3 are obtained in stainless steel bottles of V ~ 10 L resulting in a storage efficiency of ~20%. The measured UCN yields compare well with the predictions from a Monte Carlo simulation developed to model the source and to optimize its performance for the upcoming upgrade of the TRIGA Mainz into a user facility for UCN physics.Comment: 23 pages, 8 figure

Two-stage phase II oncology designs using short-term endpoints for early stopping

Phase II oncology trials are conducted to evaluate whether the tumour activity of a new treatment is promising enough to warrant further investigation. The most commonly used approach in this context is a two-stage single-arm design with binary endpoint. As for all designs with interim analysis, its efficiency strongly depends on the relation between recruitment rate and follow-up time required to measure the patients’ outcomes. Usually, recruitment is postponed after the sample size of the first stage is achieved up until the outcomes of all patients are available. This may lead to a considerable increase of the trial length and with it to a delay in the drug development process. We propose a design where an intermediate endpoint is used in the interim analysis to decide whether or not the study is continued with a second stage. Optimal and minimax versions of this design are derived. The characteristics of the proposed design in terms of type I error rate, power, maximum and expected sample size as well as trial duration are investigated. Guidance is given on how to select the most appropriate design. Application is illustrated by a phase II oncology trial in patients with advanced angiosarcoma, which motivated this research

Workshop on research p riorities for migrant pests of agriculture in Southern Africa, Plant Protection Research Institute, Pretoria, South Africa, 24–26 March 1999

The Workshop was held at the Agricultural Research Council – Plant Protection Research Institute, Pretoria, from 24 to 26 March 1999 and was attended by 66 delegates from Botswana, Malawi, Namibia, South Africa, Sudan, Swaziland, Tanzania, United Kingdom, Zimbabwe, the International Red Locust Control Organisation for Central and Southern Africa (IRLCO-CSA) and the Food and Agriculture Organization of the United Nations (FAO) (see pages xiii–xvi for list of delegates). The first day focused on presenting a synopsis of current research on the three main migrant pests in southern Africa – armyworm, locusts and quelea – and described the national, regional (IRLCO-CSA, Southern African Development Community, SADC) and international (FAO) infrastructures for dealing with them. On the second and third days, after consideration of the issues to be addressed to ensure uptake of research findings by resource-poor farmers, the Workshop divided into three groups according to pest species. Each group adopted a generalised Logical Framework approach to identifying research priorities, constraints, risks and linkages. Four Logical Frameworks, covering armyworm, locust, quelea and cross-cutting research priorities were developed and an informal ad hoc steering committee (names annotated in list, pages xiii–xvi) undertook to bring together the Workshop’s findings in a Summary Report and to make recommendations on further actions

Disruption of the GDP-mannose synthesis pathway in Streptomyces coelicolor results in antibiotic hyper-susceptible phenotypes

Actinomycete bacteria use polyprenol phosphate mannose as a lipid linked sugar donor for extra-cytoplasmic glycosyl transferases that transfer mannose to cell envelope polymers, including glycoproteins and glycolipids. We showed recently that strains of Streptomyces coelicolor with mutations in the gene ppm1 encoding polyprenol phosphate mannose synthase were both resistant to phage φC31 and have greatly increased susceptibility to antibiotics that mostly act on cell wall biogenesis. Here we show that mutations in the genes encoding enzymes that act upstream of Ppm1 in the polyprenol phosphate mannose synthesis pathway can also confer phage resistance and antibiotic hyper-susceptibility. GDP-mannose is a substrate for Ppm1 and is synthesised by GDP-mannose pyrophosphorylase (GMP; ManC) which uses GTP and mannose-1-phosphate as substrates. Phosphomannomutase (PMM; ManB) converts mannose-6-phosphate to mannose-1-phosphate. S. coelicolor strains with knocked down GMP activity or with a mutation in sco3028 encoding PMM acquire phenotypes that resemble those of the ppm1-mutants i.e. φC31 resistant and susceptible to antibiotics. Differences in the phenotypes of the strains were observed, however. While the ppm1-strains have a small colony phenotype, the sco3028 :: Tn5062 mutants had an extremely small colony phenotype indicative of an even greater growth defect. Moreover we were unable to generate a strain in which GMP activity encoded by sco3039 and sco4238 is completely knocked out, indicating that GMP is also an important enzyme for growth. Possibly GDP-mannose is at a metabolic branch point that supplies alternative nucleotide sugar donors

Leistungsorientierte Entlohnung - kann die geplante Dienstrechtsreform die Abwanderung von qualifizierten Nachwuchswissenschaftlern verhindern?

Mit der geplanten Dienstrechtsreform, die von Edelgard Bulmahn, Bundesministerin für Bildung und Forschung, vorgestellt wird, sollen Hochschullehrer in Zukunft leistungsorientiert entlohnt und für junge Nachwuchswissenschaftler bessere Arbeitsbedingungen geschaffen werden. Für Hans Zehetmair, Bayerischer Staatsminister für Wissenschaft, Forschung und Kultur, müssen die Chancen einer stärker an Leistung orientierten Professorenbesoldung genutzt werden, »denn nur so werden wir im internationalen Wettbewerb der deutschen Hochschulen um die qualifiziertesten Wissenschaftler weiterhin erfolgreich sein können«. Auf heftige Kritik stoßen diese Pläne allerdings bei den Betroffenen: Prof. Dr. Hartmut Schiedermair, Präsident des Deutschen Hochschulverbandes, Prof. Dr. Klaus M. Schmidt, Universität München, sowie Prof. Dr. Dr. h.c. Alfred Keser, Universität Mannheim, wenden sich gegen die Reformmaßnahmen und befürchten, dass »diese Reform nicht zusammen mit den Betroffenen politisch gestaltet werden soll, sondern Politik gegen die Betroffenen gemacht wird«.Deutschland; Leistungsorientierte Vergütung; Vergütungssystem; Hochschullehrer

Coronary artery bypass grafting: Part 1—the evolution over the first 50 years

Surgical treatment for angina pectoris was first proposed in 1899. Decades of experimental surgery for coronary artery disease finally led to the introduction of coronary artery bypass grafting (CABG) in 1964. Now that we are approaching 50 years of CABG experience, it is appropriate to summarize the advancement of CABG into a procedure that is safe and efficient. This review provides a historical recapitulation of experimental surgery, the evolution of the surgical techniques and the utilization of CABG. Furthermore, data on contemporary clinical outcomes are discusse

The DyP-type peroxidase DtpA is a Tat-substrate required for GlxA maturation and morphogenesis in <i>Streptomyces</i>

The filamentous bacterium Streptomyces lividans depends on the radical copper oxidase GlxA for the formation of reproductive aerial structures and, in liquid environments, for the formation of pellets. Incorporation of copper into the active site is essential for the formation of a cross-linked tyrosyl-cysteine cofactor, which is needed for enzymatic activity. In this study, we show a crucial link between GlxA maturation and a group of copper-related proteins including the chaperone Sco and a novel DyP-type peroxidase hereinafter called DtpA. Under copper-limiting conditions, the sco and dtpA deletion mutants are blocked in aerial growth and pellet formation, similarly to a glxA mutant. Western blot analysis showed that GlxA maturation is perturbed in the sco and dtpA mutants, but both maturation and morphology can by rescued by increasing the bioavailability of copper. DtpA acts as a peroxidase in the presence of GlxA and is a substrate for the twin-arginine translocation (Tat) translocation pathway. In agreement, the maturation status of GlxA is also perturbed in tat mutants, which can be compensated for by the addition of copper, thereby partially restoring their morphological defects. Our data support a model wherein a copper-trafficking pathway and Tat-dependent secretion of DtpA link to the GlxA-dependent morphogenesis pathway. </jats:p

Streptomyces coelicolor strains lacking polyprenol phosphate mannose synthase and protein O-mannosyl transferase are hyper-susceptible to multiple antibiotics

Polyprenol phosphate mannose (PPM) is a lipid-linked sugar donor used by extra-cytoplasmic glycosyl tranferases in bacteria. PPM is synthesiszed by polyprenol phosphate mannose synthase, Ppm1, and in most Actinobacteria is used as the sugar donor for protein O-mannosyl transferase, Pmt, in protein glycosylation. Ppm1 and Pmt have homologues in yeasts and humans, where they are required for protein O-mannosylation. Actinobacteria also use PPM for lipoglycan biosynthesis. Here we show that ppm1 mutants of Streptomyces coelicolor have increased susceptibility to a number of antibiotics that target cell wall biosynthesis. The pmt mutants also have mildly increased antibiotic susceptibilities, in particular to β-lactams and vancomycin. Despite normal induction of the vancomycin gene cluster, vanSRJKHAX, the pmt and ppm1 mutants remained highly vancomycin sensitive indicating that the mechanism of resistance is blocked post-transcriptionally. Differential RNA expression analysis indicated that catabolic pathways were downregulated and anabolic ones upregulated in the ppm1 mutant compared to the parent or complemented strains. Of note was the increase in expression of fatty acid biosynthetic genes in the ppm1-mutant. A change in lipid composition was confirmed using Raman spectroscopy, which showed that the ppm1-mutant had a greater relative proportion of unsaturated fatty acids compared to the parent or the complemented mutant. Taken together, these data suggest that an inability to synthesize PPM (ppm1) and loss of the glycoproteome (pmt-mutant) can detrimentally affect membrane or cell envelope functions leading to loss of intrinsic and, in the case of vancomycin, acquired antibiotic resistance