Two Immigrants with Tuberculosis of the Ear, Nose, and Throat Region with Skull Base and Cranial Nerve Involvement

We report two immigrants with tuberculosis of the skull base and a review of the literature. A Somalian man presented with bilateral otitis media, hearing loss, and facial and abducens palsy. Imaging showed involvement of both mastoid and petrous bones, extending via the skull base to the nasopharynx, suggesting tuberculosis which was confirmed by characteristic histology and positive auramine staining, while Ziehl-Neelsen staining and PCR were negative. A Sudanese man presented with torticollis and deviation of the uvula due to paresis of N. IX and XI. Imaging showed a retropharyngeal abscess and lysis of the clivus. Histology, acid-fast staining, and PCR were negative. Both patients had a positive Quantiferon TB Gold in-tube result and improved rapidly after empiric treatment for tuberculosis. Cultures eventually yielded M. tuberculosis. These unusual cases exemplify the many faces of tuberculosis and the importance to include tuberculosis in the differential diagnosis of unexplained problems

Species delimitation and DNA barcoding of Atlantic Ensis (Bivalvia, Pharidae)

[Abstract] Ensis Schumacher, 1817 razor shells occur at both sides of the Atlantic and along the Pacific coasts of tropical west America, Peru, and Chile. Many of them are marketed in various regions. However, the absence of clear autapomorphies in the shell and the sympatric distributions of some species often prevent a correct identification of specimens. As a consequence, populations cannot be properly managed, and edible species are almost always mislabelled along the production chain. In this work, we studied whether the currently accepted Atlantic Ensis morphospecies are different evolutionary lineages, to clarify their taxonomic status and enable molecular identifications through DNA barcoding. For this, we studied 109 specimens sampled at 27 sites, which were identified as belonging to nine of those morphospecies. We analysed nucleotide variation at four nuclear (18S, 5.8S, ITS1, and ITS2) and two mitochondrial (COI and 16S) regions, although the 18S and 5.8S regions were not informative at the species level and were not further considered. The phylogenetic trees and networks obtained supported all morphospecies as separately evolving lineages. Phylogenetic trees recovered Ensis at each side of the Atlantic as reciprocally monophyletic. Remarkably, we confirm the co-occurrence of the morphologically similar E. minor (Chenu, 1843) and E. siliqua (Linné, 1758) along the NW Iberian coast, a fact that has been often overlooked. In South America, a relevant divergence between E. macha (Molina, 1792) individuals from Chile and Argentina was unveiled and suggests incipient speciation. We also confirm the occurrence of the North American species E. directus (Conrad, 1843) as far south as north-eastern Florida. Among the genomic regions analysed, we suggest COI as the most suitable DNA barcode for Atlantic Ensis. Our results will contribute to the conservation and management of Ensis populations and will enable reliable identifications of the edible species, even in the absence of the valves. The name Ensis coseli Vierna nom. nov. is proposed to replace E. minor Dall, 1899 non (Chenu, 1843)

Pheromonal cues deposited by mated females convey social information about egg-laying sites in <i>Drosophila melanogaster</i>

Individuals can make choices based on information learned from others, a phenomenon called social learning. How observers differentiate between which individual they should or should not learn from is, however, poorly understood. Here, we showed that Drosophila melanogaster females can influence the choice of egg-laying site of other females through pheromonal marking. Mated females mark territories of high quality food by ejecting surplus male sperm containing the aggregation pheromone cis-11-vaccenyl acetate (cVA) and, in addition, deposit several sex- and species-specific cuticular hydrocarbon (CHC) pheromones. These pheromonal cues affect the choices of other females, which respond by preferentially laying eggs on the marked food. This system benefits both senders and responders, as communal egg laying increases offspring survival. Virgin females, however, do not elicit a change in the egg-laying decision of mated females, even when food has been supplemented with ejected sperm from mated females, thus indicating the necessity for additional cues. Genetic ablation of either a female's CHC pheromones or those of their mate results in loss of ability of mated females to attract other females. We conclude that mated females use a pheromonal marking system, comprising cVA acquired from male ejaculate with sex- and species-specific CHCs produced by both mates, to indicate egg-laying sites. This system ensures information reliability because mated, but not virgin, females have both the ability to generate the pheromone blend that attracts other flies to those sites and a direct interest in egg-laying site quality

An experimental study on the effects of a simulation game on students’ clinical cognitive skills and motivation

Simulation games are becoming increasingly popular in education, but more insight in their critical design features is needed. This study investigated the effects of fidelity of open patient cases in adjunct to an instructional e-module on students’ cognitive skills and motivation. We set up a three-group randomized post-test-only design: a control group working on an e-module; a cases group, combining the e-module with low-fidelity text-based patient cases, and a game group, combining the e-module with a high-fidelity simulation game with the same cases. Participants completed questionnaires on cognitive load and motivation. After a 4-week study period, blinded assessors rated students’ cognitive emergency care skills in two mannequin-based scenarios. In total 61 students participated and were assessed; 16 control group students, 20 cases students and 25 game students. Learning time was 2 h longer for the cases and game groups than for the control group. Acquired cognitive skills did not differ between groups. The game group experienced higher intrinsic and germane cognitive load than the cases group (p = 0.03 and 0.01) and felt more engaged (p < 0.001). Students did not profit from working on open cases (in adjunct to an e-module), which nonetheless challenged them to study longer. The e-module appeared to be very effective, while the high-fidelity game, although engaging, probably distracted students and impeded learning. Medical educators designing motivating and effective skills training for novices should align case complexity and fidelity with students’ proficiency level. The relation between case-fidelity, motivation and skills development is an important field for further study

An experimental study on the effects of a simulation game on students’ clinical cognitive skills and motivation

textabstractSimulation games are becoming increasingly popular in education, but more insight in their critical design features is needed. This study investigated the effects of fidelity of open patient cases in adjunct to an instructional e-module on students’ cognitive skills and motivation. We set up a three-group randomized post-test-only design: a control group working on an e-module; a cases group, combining the e-module with low-fidelity text-based patient cases, and a game group, combining the e-module with a high-fidelity simulation game with the same cases. Participants completed questionnaires on cognitive load and motivation. After a 4-week study period, blinded assessors rated students’ cognitive emergency care skills in two mannequin-based scenarios. In total 61 students participated and were assessed; 16 control group students, 20 cases students and 25 game students. Learning time was 2 h longer for the cases and game groups than for the control group. Acquired cognitive skills did not differ between groups. The game group experienced higher intrinsic and germane cognitive load than the cases group (p = 0.03 and 0.01) and felt more engaged (p < 0.001). Students did not profit from working on open cases (in adjunct to an e-module), which nonetheless challenged them to study longer. The e-module appeared to be very effective, while the high-fidelity game, although engaging, probably distracted students and impeded learning. Medical educators designing motivating and effective skills training for novices should align case complexity and fidelity with students’ proficiency level. The relation between case-fidelity, motivation and skills development is an important field for further study

Comorbidity, not patient age, is associated with impaired safety outcomes in vedolizumab- and ustekinumab-treated patients with inflammatory bowel disease-a prospective multicentre cohort study

Background: Few data are available on the effects of age and comorbidity on treatment outcomes of vedolizumab and ustekinumab in inflammatory bowel disease (IBD). Aims: To evaluate the association between age and comorbidity with safety and effectiveness outcomes of vedolizumab and ustekinumab in IBD. Methods: IBD patients initiating vedolizumab or ustekinumab in regular care were enrolled prospectively. Comorbidity prevalence was assessed using the Charlson Comorbidity Index (CCI). Association between age and CCI, both continuously assessed, with safety outcomes (any infection, hospitalisation, adverse events) during treatment, and effectiveness outcomes (clinical response and remission, corticosteroid-free remission, clinical remission combined with biochemical remission) after 52 weeks of treatment were evaluated. Multivariable logistic regression was used to adjust for confounders. Results: We included 203 vedolizumab- and 207 ustekinumab-treated IBD patients, mean age 42.2 (SD 16.0) and 41.6 (SD 14.4). Median treatment duration 54.0 (IQR 19.9-104.0) and 48.4 (IQR 24.4-55.1) weeks, median follow-up time 104.0 (IQR 103.1-104.0) and 52.0 weeks (IQR 49.3-100.4). On vedolizumab, CCI associated independently with any infection (OR 1.387, 95% CI 1.022-1.883, P = 0.036) and hospitalisation (OR 1.586, 95% CI 1.127-2.231, P = 0.008). On ustekinumab, CCI associated independently with hospitalisation (OR 1.621, 95% CI 1.034-2.541, P = 0.035). CCI was not associated with effectiveness, and age was not associated with any outcomes. Conclusions: Comorbidity - but not age - is associated with an increased risk of hospitalisations on either treatment, and with any infection on vedolizumab. This underlines the importance of comorbidity assessment and safety monitoring of IBD patients

Investigation of the Domain Wall Fermion Approach to Chiral Gauge Theories on the Lattice

We investigate a recent proposal to construct chiral gauge theories on the lattice using domain wall fermions. We restrict ourselves to the finite volume case, in which two domain walls are present, with modes of opposite chirality on each of them. We couple the chiral fermions on only one of the domain walls to a gauge field. In order to preserve gauge invariance, we have to add a scalar field, which gives rise to additional light mirror fermion and scalar modes. We argue that in an anomaly free model these extra modes would decouple if our model possesses a so-called strong coupling symmetric phase. However, our numerical results indicate that such a phase most probably does not exist. ---- Note: 9 Postscript figures are appended as uuencoded compressed tar file.Comment: 27p. Latex; UCSD/PTH 93-28, Wash. U. HEP/93-6

Novel chemistry of invasive plants: exotic species have more unique 1 metabolomic profiles than native congeners 2 3

and their native congeners of the family Asteraceae. Our results showed that plant chemistry is 51 highly species-specific and diverse among both exotic and native species. Nonetheless, the exotic 52 species had on average a higher total number of metabolites and more species-unique 53 metabolites compared to their native congeners. Herbivory led to an overall increase of 54 metabolites in all plant species. Generalist herbivore performance was lower on most of the 55 exotic species compared to the native species. We conclude that high chemical diversity and 56 large phytochemical uniqueness of the exotic species could be indicative of biological invasion 57 potential

Individual differences in metabolomics: individualised responses and between-metabolite relationships

Many metabolomics studies aim to find ‘biomarkers’: sets of molecules that are consistently elevated or decreased upon experimental manipulation. Biological effects, however, often manifest themselves along a continuum of individual differences between the biological replicates in the experiment. Such differences are overlooked or even diminished by methods in standard use for metabolomics, although they may contain a wealth of information on the experiment. Properly understanding individual differences is crucial for generating knowledge in fields like personalised medicine, evolution and ecology. We propose to use simultaneous component analysis with individual differences constraints (SCA-IND), a data analysis method from psychology that focuses on these differences. This method constructs axes along the natural biochemical differences between biological replicates, comparable to principal components. The model may shed light on changes in the individual differences between experimental groups, but also on whether these differences correspond to, e.g., responders and non-responders or to distinct chemotypes. Moreover, SCA-IND reveals the individuals that respond most to a manipulation and are best suited for further experimentation. The method is illustrated by the analysis of individual differences in the metabolic response of cabbage plants to herbivory. The model reveals individual differences in the response to shoot herbivory, where two ‘response chemotypes’ may be identified. In the response to root herbivory the model shows that individual plants differ strongly in response dynamics. Thereby SCA-IND provides a hitherto unavailable view on the chemical diversity of the induced plant response, that greatly increases understanding of the system

Between Metabolite Relationships: an essential aspect of metabolic change

Not only the levels of individual metabolites, but also the relations between the levels of different metabolites may indicate (experimentally induced) changes in a biological system. Component analysis methods in current ‘standard’ use for metabolomics, such as Principal Component Analysis (PCA), do not focus on changes in these relations. We therefore propose the concept of ‘Between Metabolite Relationships’ (BMRs): common changes in the covariance (or correlation) between all metabolites in an organism. Such structural changes may indicate metabolic change brought about by experimental manipulation but which are lost with standard data analysis methods. These BMRs can be analysed by the INdividual Differences SCALing (INDSCAL) method. First the BMR quantification is described and subsequently the INDSCAL method. Finally, two studies illustrate the power and the applicability of BMRs in metabolomics. The first study is about the induced plant response of cabbage to herbivory, of which BMRs are a considerable part. In the second study—a human nutritional intervention study of green tea extract—standard data analysis tools did not reveal any metabolic change, although the BMRs were considerably affected. The presented results show that BMRs can be easily implemented in a wide variety of metabolomic studies. They provide a new source of information to describe biological systems in a way that fits flawlessly into the next generation of systems biology questions, dealing with personalized responses