Occurrence of testicular microlithiasis in androgen insensitive hypogonadal mice

<b>Background</b>: Testicular microliths are calcifications found within the seminiferous tubules. In humans, testicular microlithiasis (TM) has an unknown etiology but may be significantly associated with testicular germ cell tumors. Factors inducing microlith development may also, therefore, act as susceptibility factors for malignant testicular conditions. Studies to identify the mechanisms of microlith development have been hampered by the lack of suitable animal models for TM.<BR/> <b>Methods</b>: This was an observational study of the testicular phenotype of different mouse models. The mouse models were: cryptorchid mice, mice lacking androgen receptors (ARs) on the Sertoli cells (SCARKO), mice with a ubiquitous loss of androgen ARs (ARKO), hypogonadal (hpg) mice which lack circulating gonadotrophins, and hpg mice crossed with SCARKO (hpg.SCARKO) and ARKO (hpg.ARKO) mice.<BR/> <b>Results</b>: Microscopic TM was seen in 94% of hpg.ARKO mice (n=16) and the mean number of microliths per testis was 81 +/- 54. Occasional small microliths were seen in 36% (n=11) of hpg testes (mean 2 +/- 0.5 per testis) and 30% (n=10) of hpg.SCARKO testes (mean 8 +/- 6 per testis). No microliths were seen in cryptorchid, ARKO or SCARKO mice. There was no significant effect of FSH or androgen on TM in hpg.ARKO mice.<BR/> <b>Conclusions</b>: We have identified a mouse model of TM and show that lack of endocrine stimulation is a cause of TM. Importantly, this model will provide a means with which to identify the mechanisms of TM development and the underlying changes in protein and gene expression

Science Models as Value-Added Services for Scholarly Information Systems

The paper introduces scholarly Information Retrieval (IR) as a further dimension that should be considered in the science modeling debate. The IR use case is seen as a validation model of the adequacy of science models in representing and predicting structure and dynamics in science. Particular conceptualizations of scholarly activity and structures in science are used as value-added search services to improve retrieval quality: a co-word model depicting the cognitive structure of a field (used for query expansion), the Bradford law of information concentration, and a model of co-authorship networks (both used for re-ranking search results). An evaluation of the retrieval quality when science model driven services are used turned out that the models proposed actually provide beneficial effects to retrieval quality. From an IR perspective, the models studied are therefore verified as expressive conceptualizations of central phenomena in science. Thus, it could be shown that the IR perspective can significantly contribute to a better understanding of scholarly structures and activities.Comment: 26 pages, to appear in Scientometric

The relationship between quality of research and citation frequency

BACKGROUND: Citation counts are often regarded as a measure of the utilization and contribution of published articles. The objective of this study is to assess whether statistical reporting and statistical errors in the analysis of the primary outcome are associated with the number of citations received. METHODS: We evaluated all original research articles published in 1996 in four psychiatric journals. The statistical and reporting quality of each paper was assessed and the number of citations received up to 2005 was obtained from the Web of Science database. We then examined whether the number of citations was associated with the quality of the statistical analysis and reporting. RESULTS: A total of 448 research papers were included in the citation analysis. Unclear or inadequate reporting of the research question and primary outcome were not statistically significantly associated with the citation counts. After adjusting for journal, extended description of statistical procedures had a positive effect on the number of citations received. Inappropriate statistical analysis did not affect the number of citations received. Adequate reporting of the primary research question, statistical methods and primary findings were all associated with the journal visibility and prestige. CONCLUSION: In this cohort of published research, measures of reporting quality and appropriate statistical analysis were not associated with the number of citations. The journal in which a study is published appears to be as important as the statistical reporting quality in ensuring dissemination of published medical science

Mixed emotions to near-miss outcomes: a psychophysiological study with facial electromyography

Near-misses occur across many forms of gambling and are rated as unpleasant while simultaneously increasing the motivation to continue playing. On slot machines, the icon position relative to the payline moderates the effects of near-misses, with near-misses before the payline increasing motivation, and near-misses after the payline being rated as aversive. Near-misses are also known to increase physiological arousal compared to full-misses, but physiological measures to date have not been able to dissociate positive and negative emotional responses. The present study measured facial electromyography at the corrugator (brow) and zygomaticus (cheek) sites, as well as electrodermal activity (EDA), following gambling outcomes on a two-reel slot machine simulation in 77 novice gamblers. Behavioral data was collected using trial-by-trial ratings of motivation and valence. Wins were rated as more pleasant and increased motivation to continue playing, compared to non-win outcomes. Wins were also accompanied by increased EDA and zygomaticus activity. Near-misses after the payline were rated as more aversive than other non-wins, and this was accompanied by increased EDA and zygomaticus activity. Near-misses before the payline increased motivation to continue playing, and were accompanied by increased EDA. Thus, both subjective and physiological responses to near-misses differ for events falling either side of the payline. The ‘near-miss effect’ is not a unitary phenomenon. Facial EMG has differential sensitivity to positive and negative valence and may be a useful measure for future studies of gambling behavior

The Mechanisms of Codon Reassignments in Mitochondrial Genetic Codes

Many cases of non-standard genetic codes are known in mitochondrial genomes. We carry out analysis of phylogeny and codon usage of organisms for which the complete mitochondrial genome is available, and we determine the most likely mechanism for codon reassignment in each case. Reassignment events can be classified according to the gain-loss framework. The gain represents the appearance of a new tRNA for the reassigned codon or the change of an existing tRNA such that it gains the ability to pair with the codon. The loss represents the deletion of a tRNA or the change in a tRNA so that it no longer translates the codon. One possible mechanism is Codon Disappearance, where the codon disappears from the genome prior to the gain and loss events. In the alternative mechanisms the codon does not disappear. In the Unassigned Codon mechanism, the loss occurs first, whereas in the Ambiguous Intermediate mechanism, the gain occurs first. Codon usage analysis gives clear evidence of cases where the codon disappeared at the point of the reassignment and also cases where it did not disappear. Codon disappearance is the probable explanation for stop to sense reassignments and a small number of reassignments of sense codons. However, the majority of sense to sense reassignments cannot be explained by codon disappearance. In the latter cases, by analysis of the presence or absence of tRNAs in the genome and of the changes in tRNA sequences, it is sometimes possible to distinguish between the Unassigned Codon and Ambiguous Intermediate mechanisms. We emphasize that not all reassignments follow the same scenario and that it is necessary to consider the details of each case carefully.Comment: 53 pages (45 pages, including 4 figures + 8 pages of supplementary information). To appear in J.Mol.Evo

Experience and Challenges from Clinical Trials with Malaria Vaccines in Africa.

Malaria vaccines are considered amongst the most important modalities for potential elimination of malaria disease and transmission. Research and development in this field has been an area of intense effort by many groups over the last few decades. Despite this, there is currently no licensed malaria vaccine. Researchers, clinical trialists and vaccine developers have been working on many approached to make malaria vaccine available.African research institutions have developed and demonstrated a great capacity to undertake clinical trials in accordance to the International Conference on Harmonization-Good Clinical Practice (ICH-GCP) standards in the last decade; particularly in the field of malaria vaccines and anti-malarial drugs. This capacity is a result of networking among African scientists in collaboration with other partners; this has traversed both clinical trials and malaria control programmes as part of the Global Malaria Action Plan (GMAP). GMAP outlined and support global strategies toward the elimination and eradication of malaria in many areas, translating in reduction in public health burden, especially for African children. In the sub-Saharan region the capacity to undertake more clinical trials remains small in comparison to the actual need.However, sustainability of the already developed capacity is essential and crucial for the evaluation of different interventions and diagnostic tools/strategies for other diseases like TB, HIV, neglected tropical diseases and non-communicable diseases. There is urgent need for innovative mechanisms for the sustainability and expansion of the capacity in clinical trials in sub-Saharan Africa as the catalyst for health improvement and maintained

Off-shell superconformal nonlinear sigma-models in three dimensions

We develop superspace techniques to construct general off-shell N=1,2,3,4 superconformal sigma-models in three space-time dimensions. The most general N=3 and N=4 superconformal sigma-models are constructed in terms of N=2 chiral superfields. Several superspace proofs of the folklore statement that N=3 supersymmetry implies N=4 are presented both in the on-shell and off-shell settings. We also elaborate on (super)twistor realisations for (super)manifolds on which the three-dimensional N-extended superconformal groups act transitively and which include Minkowski space as a subspace.Comment: 67 pages; V2: typos corrected, one reference added, version to appear on JHE