Design and validation of a German version of the GSRS-IBS - an analysis of its psychometric quality and factorial structure

Background: Currently, a suitable questionnaire in German language is not available to monitor the progression and evaluate the severity of irritable bowel syndrome (IBS). Therefore, this study aimed to translate the Gastrointestinal Symptom Rating Scale for Irritable Bowel Syndrome (GSRS-IBS) into German and to evaluate its psychometric qualities and factorial structure. Methods: This study is based on a total sample of 372 participants [62.6% female, mean age = 41 years (SD = 17 years)]. 17.5% of the participants had a diagnosis of IBS, 19.9% were receiving treatment for chronic inflammatory bowel disease, 12.1% of the participants were recruited from a psychosomatic clinic, and 50.5% belonged to a control group. All participants completed the German version of GSRS-IBS (called Reizdarm-Fragebogen, RDF), as well as the Gießen Subjective Complaints List (GBB-24) and the Hospital Anxiety and Depression Scale - German version (HADS-D). Results: The internal consistency of the RDF total scale was at least satisfactory in all subsamples (Cronbach’s Alpha between .77 and .92), and for all subscales (Cronbach’s Alpha between .79 and .91). The item difficulties (between .25 and .73) and the item-total correlations (between .48 and .83) were equally satisfactory. Principal axis analysis revealed a four-factorial structure of the RDF items, which mainly resembled the structure of the English original. Convergent validity was established based on substantial and significant correlations with the stomach-complaint scale of the GBB-24 (r = .71; p < .01) and the anxiety (r = .42; p < .01) and depression scales (r = .43; p < .01) of the HADS-D. Conclusion: The German version of the GSRS-IBS RDF proves to be an effective, reliable, and valid questionnaire for the assessment of symptom severity in IBS, which can be used in clinical practice as well as in clinical studies

Inter-cultural differences in response to a computer-based anti-bullying intervention

Background and purpose: Many holistic anti-bullying interventions have been attempted, with mixed success, while little work has been done to promote a 'self-help' approach to victimisation. The rise of the ICT curriculum and computer support in schools now allows for approaches that benefit from technology to be implemented. This study evaluates the cross-cultural effects of a computer-based anti-bullying intervention on primary school-aged children's knowledge about bullying and relevant coping strategies. Programme description: FearNot! is an interactive computer-based virtual learning environment designed for use as an anti-bullying intervention. It includes interactive virtual agents who assume the most common participant roles found in episodes of bullying. FearNot! was used by children over three consecutive weeks to allow its effectiveness to be evaluated in a longitudinal in situ programme. Sample: Two comparable samples were drawn from the UK and Germany. In the UK, 651 participants (aged 8-11) were recruited from primary schools in Hertfordshire, Coventry and Warwickshire, whereas the 535 German participants (aged 7-10) were sourced from Grundschulen in the Bayern and Hessen regions. Because of lack of parental consent, late joiners and absences/missing responses, data from 908 participants (UK 493; Germany 415) were analysed. Design and methods: A quasi-experimental, pre/post-tests control group design employed pre-published and bespoke questionnaires to collect data. Descriptive and inferential analyses were conducted. Results: UK students possessed higher coping strategy knowledge scores than German participants, but German children's scores improved over time and as a result of the FearNot! intervention. Conclusions: Overall, while not effective at increasing children's coping strategy knowledge in this study, the FearNot! intervention could prove a useful classroom tool to approach the issue of bullying as part of a wider initiative. Cultural differences at baseline and reactions to the intervention are discussed

Fighting misinformation in seismology: Expert opinion on earthquake facts vs. fiction

Misinformation carries the potential for immense damage to public understanding of science and for evidence-based decision making at an individual and policy level. Our research explores the following questions within seismology: which claims can be considered misinformation, which are supported by a consensus, and which are still under scientific debate? Consensus and debate are important to quantify, because where levels of scientific consensus on an issue are high, communication of this fact may itself serve as a useful tool in combating misinformation. This is a challenge for earthquake science, where certain theories and facts in seismology are still being established. The present study collates a list of common public statements about earthquakes and provides–to the best of our knowledge–the first elicitation of the opinions of 164 earth scientists on the degree of verity of these statements. The results provide important insights for the state of knowledge in the field, helping identify those areas where consensus messaging may aid in the fight against earthquake related misinformation and areas where there is currently lack of consensus opinion. We highlight the necessity of using clear, accessible, jargon-free statements with specified parameters and precise wording when communicating with the public about earthquakes, as well as of transparency about the uncertainties around some issues in seismology

Telomeric expression sites are highly conserved in trypanosoma brucei

Subtelomeric regions are often under-represented in genome sequences of eukaryotes. One of the best known examples of the use of telomere proximity for adaptive purposes are the bloodstream expression sites (BESs) of the African trypanosome Trypanosoma brucei. To enhance our understanding of BES structure and function in host adaptation and immune evasion, the BES repertoire from the Lister 427 strain of T. brucei were independently tagged and sequenced. BESs are polymorphic in size and structure but reveal a surprisingly conserved architecture in the context of extensive recombination. Very small BESs do exist and many functioning BESs do not contain the full complement of expression site associated genes (ESAGs). The consequences of duplicated or missing ESAGs, including ESAG9, a newly named ESAG12, and additional variant surface glycoprotein genes (VSGs) were evaluated by functional assays after BESs were tagged with a drug-resistance gene. Phylogenetic analysis of constituent ESAG families suggests that BESs are sequence mosaics and that extensive recombination has shaped the evolution of the BES repertoire. This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology

Adjuvant formulated virus-like particles expressing native-like forms of the Lassa virus envelope surface glycoprotein are immunogenic and induce antibodies with broadly neutralizing activity

Lassa mammarenavirus (LASV) is a rodent-borne arenavirus endemic to several West African countries. It is the causative agent of human Lassa fever, an acute viral hemorrhagic fever disease. To date, no therapeutics or vaccines against LASV have obtained regulatory approval. Polyclonal neutralizing antibodies derived from hyperimmunized animals may offer a useful strategy for prophylactic and therapeutic intervention to combat human LASV infections. The LASV envelope surface glycoprotein complex (GP) is the major target for neutralizing antibodies, and it is the main viral antigen used for the design of an LASV vaccine. Here, we assessed the immunogenic potential of mammalian cell-derived virus-like particles (VLPs) expressing GP from the prototypic LASV strain Josiah in a native-like conformation as the sole viral antigen. We demonstrate that an adjuvanted prime-boost immunization regimen with GP-derived VLPs elicited neutralizing antibody responses in rabbits, suggesting that effective antigenic epitopes of GP were displayed. Notably, these antibodies exhibited broad reactivity across five genetic lineages of LASV. VLP-based immunization strategies may represent a powerful approach for generating polyclonal sera containing cross-reactive neutralizing antibodies against LASV

The role of neuroactive steroids in ethanol/stress interactions: proceedings of symposium VII at the Volterra conference on alcohol and stress, May 2008

This report summarizes the proceedings of the symposium VII on the role of neuroactive steroids in stress/alcohol interactions. The production of GABAergic neuroactive steroids, including (3α,5α)-3-hydroxypregnan-20-one (3α,5α-THP) and (3α,5α)-3,21-dihydroxypregnan-20-one (3α,5α-THDOC) is a consequence of both acute stress and acute ethanol exposure. Acute, but not chronic ethanol administration elevates brain levels of these steroids and enhances GABAA receptor activity. Neuroactive steroids modulate acute anticonvulsant effects, sedation, spatial memory impairment, anxiolytic-like, antidepressant-like and reinforcing properties of ethanol in rodents. Furthermore, these steroids participate in the homeostatic regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Therefore, it is not surprising that neuroactive steroids are involved in ethanol/stress interactions. Nevertheless, the interactions are complex and not well understood. This symposium addressed the role of neuroactive steroids in both stress and alcohol responses and their interactions. Professor Giovanni Biggio of the University of Cagliari, Italy presented the effects of juvenile isolation stress on neuroactive steroids, GABAA receptor expression and ethanol sensitivity. Professor Howard Becker of the Medical University of South Carolina, USA presented evidence for neuroactive steroid involvement in ethanol dependence and drinking behavior. Professor Patrizia Porcu of the University of North Carolina, USA described a potential neuroactive steroid biomarker that may predict heavy drinking in monkeys and mice. These presentations provide a framework for new theories on the nature of ethanol/stress interactions that may be amenable to therapeutic interventions

The WiggleZ Dark Energy Survey: Survey Design and First Data Release

The WiggleZ Dark Energy Survey is a survey of 240,000 emission line galaxies in the distant universe, measured with the AAOmega spectrograph on the 3.9-m Anglo-Australian Telescope (AAT). The target galaxies are selected using ultraviolet photometry from the GALEX satellite, with a flux limit of NUV<22.8 mag. The redshift range containing 90% of the galaxies is 0.2<z<1.0. The primary aim of the survey is to precisely measure the scale of baryon acoustic oscillations (BAO) imprinted on the spatial distribution of these galaxies at look-back times of 4-8 Gyrs. Detailed forecasts indicate the survey will measure the BAO scale to better than 2% and the tangential and radial acoustic wave scales to approximately 3% and 5%, respectively. This paper provides a detailed description of the survey and its design, as well as the spectroscopic observations, data reduction, and redshift measurement techniques employed. It also presents an analysis of the properties of the target galaxies, including emission line diagnostics which show that they are mostly extreme starburst galaxies, and Hubble Space Telescope images, which show they contain a high fraction of interacting or distorted systems. In conjunction with this paper, we make a public data release of data for the first 100,000 galaxies measured for the project.Comment: Accepted by MNRAS; this has some figures in low resolution format. Full resolution PDF version (7MB) available at http://www.physics.uq.edu.au/people/mjd/pub/wigglez1.pdf The WiggleZ home page is at http://wigglez.swin.edu.au

Common folate gene variant, MTHFR C677T, is associated with brain structure in two independent cohorts of people with mild cognitive impairment☆

A commonly carried C677T polymorphism in a folate-related gene, MTHFR, is associated with higher plasma homocysteine, a well-known mediator of neuronal damage and brain atrophy. As homocysteine promotes brain atrophy, we set out to discover whether people carrying the C677T MTHFR polymorphism which increases homocysteine, might also show systematic differences in brain structure. Using tensor-based morphometry, we tested this association in 359 elderly Caucasian subjects with mild cognitive impairment (MCI) (mean age: 75 ± 7.1 years) scanned with brain MRI and genotyped as part of Alzheimer's Disease Neuroimaging Initiative. We carried out a replication study in an independent, non-overlapping sample of 51 elderly Caucasian subjects with MCI (mean age: 76 ± 5.5 years), scanned with brain MRI and genotyped for MTHFR, as part of the Cardiovascular Health Study. At each voxel in the brain, we tested to see where regional volume differences were associated with carrying one or more MTHFR ‘T’ alleles. In ADNI subjects, carriers of the MTHFR risk allele had detectable brain volume deficits, in the white matter, of up to 2–8% per risk T allele locally at baseline and showed accelerated brain atrophy of 0.5–1.5% per T allele at 1 year follow-up, after adjusting for age and sex. We replicated these brain volume deficits of up to 5–12% per MTHFR T allele in the independent cohort of CHS subjects. As expected, the associations weakened after controlling for homocysteine levels, which the risk gene affects. The MTHFR risk variant may thus promote brain atrophy by elevating homocysteine levels. This study aims to investigate the spatially detailed effects of this MTHFR polymorphism on brain structure in 3D, pointing to a causal pathway that may promote homocysteine-mediated brain atrophy in elderly people with MCI

AGEMAP: A Gene Expression Database for Aging in Mice

We present the AGEMAP (Atlas of Gene Expression in Mouse Aging Project) gene expression database, which is a resource that catalogs changes in gene expression as a function of age in mice. The AGEMAP database includes expression changes for 8,932 genes in 16 tissues as a function of age. We found great heterogeneity in the amount of transcriptional changes with age in different tissues. Some tissues displayed large transcriptional differences in old mice, suggesting that these tissues may contribute strongly to organismal decline. Other tissues showed few or no changes in expression with age, indicating strong levels of homeostasis throughout life. Based on the pattern of age-related transcriptional changes, we found that tissues could be classified into one of three aging processes: (1) a pattern common to neural tissues, (2) a pattern for vascular tissues, and (3) a pattern for steroid-responsive tissues. We observed that different tissues age in a coordinated fashion in individual mice, such that certain mice exhibit rapid aging, whereas others exhibit slow aging for multiple tissues. Finally, we compared the transcriptional profiles for aging in mice to those from humans, flies, and worms. We found that genes involved in the electron transport chain show common age regulation in all four species, indicating that these genes may be exceptionally good markers of aging. However, we saw no overall correlation of age regulation between mice and humans, suggesting that aging processes in mice and humans may be fundamentally different

Central topography of cranial motor nuclei controlled by differential cadherin expression

Neuronal nuclei are prominent, evolutionarily conserved features of vertebrate central nervous system (CNS) organization [1]. Nuclei are clusters of soma of functionally related neurons and are located in highly stereotyped positions. Establishment of this CNS topography is critical to neural circuit assembly. However, little is known of either the cellular or molecular mechanisms that drive nucleus formation during development, a process termed nucleogenesis [2, 3, 4, 5]. Brainstem motor neurons, which contribute axons to distinct cranial nerves and whose functions are essential to vertebrate survival, are organized exclusively as nuclei. Cranial motor nuclei are composed of two main classes, termed branchiomotor/visceromotor and somatomotor [6]. Each of these classes innervates evolutionarily distinct structures, for example, the branchial arches and eyes, respectively. Additionally, each class is generated by distinct progenitor cell populations and is defined by differential transcription factor expression [7, 8]; for example, Hb9 distinguishes somatomotor from branchiomotor neurons. We characterized the time course of cranial motornucleogenesis, finding that despite differences in cellular origin, segregation of branchiomotor and somatomotor nuclei occurs actively, passing through a phase of each being intermingled. We also found that differential expression of cadherin cell adhesion family members uniquely defines each motor nucleus. We show that cadherin expression is critical to nucleogenesis as its perturbation degrades nucleus topography predictably