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

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

Controlling bias and inflation in epigenome- and transcriptome-wide association studies using the empirical null distribution

We show that epigenome- and transcriptome-wide association studies (EWAS and TWAS) are prone to significant inflation and bias of test statistics, an unrecognized phenomenon introducing spurious findings if left unaddressed. Neither GWAS-based methodology nor state-of-the-art confounder adjustment methods completely remove bias and inflation. We propose a Bayesian method to control bias and inflation in EWAS and TWAS based on estimation of the empirical null distribution. Using simulations and real data, we demonstrate that our method maximizes power while properly controlling the false positive rate. We illustrate the utility of our method in large-scale EWAS and TWAS meta-analyses of age and smoking.</p

Economic evaluation of posaconazole versus fluconazole prophylaxis in patients with graft-versus-host disease (GVHD) in the Netherlands

The objective of this study was to evaluate the cost-effectiveness of posaconazole versus fluconazole for the prevention of invasive fungal infections (IFI) in graft-versus-host disease (GVHD) patients in the Netherlands. A decision analytic model was developed based on a double-blind randomized trial that compared posaconazole with fluconazole antifungal prophylaxis in recipients of allogeneic HSCT with GVHD who were receiving immunosuppressive therapy (Ullmann et al., N Engl J Med 356:335–347, 2007). Clinical events were modeled with chance nodes reflecting probabilities of IFIs, IFI-related death, and death from other causes. Data on life expectancy, quality-of-life, medical resource consumption, and costs were obtained from the literature. The total cost with posaconazole amounted to €9,428 (95% uncertainty interval €7,743–11,388), which is €4,566 (€2,460–6,854) more than those with fluconazole. Posaconazole prophylaxis resulted in 0.17 (0.02–0.36) quality adjusted life year (QALY) gained compared to fluconazole prophylaxis, corresponding to an incremental cost effectiveness ratio (ICER) of €26,225 per QALY gained. A scenario analysis demonstrated that at an increased background IFI risk (from 9% to 15%) the ICER was €13,462 per QALY. Given the underlying data and assumptions, posaconazole prophylaxis is expected to be cost-effective relative to fluconazole in recipients of allogeneic HSCT developing GVHD in the Netherlands. The cost-effectiveness of posaconazole depends on the IFI risk, which can vary by hospital

Platelet degranulation and bleeding phenotype in a large cohort of Von Willebrand disease patients

Von Willebrand disease (VWD) is a bleeding disorder caused by quantitative (type 1 or 3) or qualitative (type 2A/2B/2M/2N) defects of circulating von Willebrand factor (VWF). Circulating VWF levels not always fully explain bleeding phenotypes, suggesting a role for alternative factors, like platelets. Here, we investigated platelet factor 4 (PF4) in a large cohort of patients with VWD. PF4 levels were lower in type 2B and current bleeding phenotype was significantly associated with higher PF4 levels, particularly in type 1 VWD. Based on our findings we speculate that platelet degranulation and cargo release may play a role across VWD subtypes