Is sirolimus a therapeutic option for patients with progressive pulmonary lymphangioleiomyomatosis?

<p>Abstract</p> <p>Background</p> <p>Lymphangioleiomyomatosis (LAM) is a rare lung disease characterised by progressive airflow obstruction. No effective medical treatment is available but therapy with sirolimus has shown some promise. The aim of this observational study was to evaluate sirolimus in progressive LAM.</p> <p>Methods</p> <p>Sirolimus (trough level 5 - 10 ng/ml) was administered to ten female patients (42.4 ± 11.9 years) with documented progression. Serial pulmonary function tests and six-minute-walk-distance (6-MWD) assessments were performed.</p> <p>Results</p> <p>The mean loss of FEV₁was -2.30 ± 0.52 ml/day before therapy and a significant mean gain of FEV₁of 1.19 ± 0.26 ml/day was detected during treatment (p = 0.001). Mean FEV₁and FVC at baseline were 1.12 ± 0.15 l (36.1 ± 4.5%pred.) and 2.47 ± 0.25 l (69.2 ± 6.5%pred.), respectively. At three and six months during follow-up a significant increase of FEV₁and FVC was demonstrated (3 months ΔFEV₁: 220 ± 82 ml, p = 0.024; 6 months ΔFEV₁: 345 ± 58 ml, p = 0.001); (3 months ΔFVC: 360 ± 141 ml, p = 0.031; 6 months ΔFVC: 488 ± 138 ml, p = 0.006). Sirolimus was discontinued in 3 patients because of serious recurrent lower respiratory tract infection or sirolimus-induced pneumonitis. No deaths and no pneumothoraces occurred during therapy.</p> <p>Conclusions</p> <p>Our data suggest that sirolimus might be considered as a therapeutic option in rapidly declining LAM patients. However, sirolimus administration may be associated with severe respiratory adverse events requiring treatment cessation in some patients. Moreover, discontinuation of sirolimus is mandatory prior to lung transplantation.</p

Reciprocal Kit-Building of Concept Map to Share Each Other's Understanding as Preparation for Collaboration

Collaborative learning is an active teaching and learning strategy, in which learners who give each other elaborated explanations can learn most. However, it is difficult for learners to explain their own understanding elaborately in collaborative learning. In this study, we propose a collaborative use of a Kit-Build concept map (KB map) called “Reciprocal KB map”. In a Reciprocal KB map for a pair discussion, at first, the two participants make their own concept maps expressing their comprehension. Then, they exchange the components of their maps and request each other to reconstruct their maps by using the components. The differences between the original concept map and the reconstructed map are diagnosed automatically as an advantage of the KB map. Reciprocal KB map is expected to encourage pair discussion to recognize the understanding of each other and to create an effective discussion. In an experiment reported in this paper, Reciprocal KB map was used for supporting a pair discussion and was compared with a pair discussion which was supported by a traditional concept map. Nineteen pairs of university students were requested to use the traditional concept map in their discussion, while 20 pairs of university students used Reciprocal KB map for discussing the same topic. The results of the experiment were analyzed using three metrics: a discussion score, a similarity score, and questionnaires. The discussion score, which investigates the value of talk in discussion, demonstrates that Reciprocal KB map can promote more effective discussion between the partners compared to the traditional concept map. The similarity score, which evaluates the similarity of the concept maps, demonstrates that Reciprocal KB map can encourage the pair of partners to understand each other better compared to the traditional concept map. Last, the questionnaires illustrate that Reciprocal KB map can support the pair of partners to collaborate in the discussion smoothly and that the participants accepted this method for sharing their understanding with each other. These results suggest that Reciprocal KB map is a promising approach for encouraging pairs of partners to understand each other and to promote the effective discussions.This work was partially supported by JSPS KAKENHI Grant Number 17H01839 and 15H02931.'Artificial Intelligence in Education' 19th International Conference, AIED 2018, London, UK, June 27–30, 2018, Proceedings, Part

Stress in nurses : stress-related affect and its determinants examined over the nursing day

Peer reviewedPostprin

The Winter Worries of Bats : Past and Present Perspectives on Winter Habitat and Management of Cave Hibernating Bats

Winter is a time of fascinating changes in biology for cave-hibernating bats, but it is also a time of vulnerability. Unsurprisingly, assessments of winter habitat for these mammals and how it can be managed have been a focus of many researchers involved with the North American Society for Bat Research over the last 50 years. Over this time, a paradigm shift has occurred in the way scientists think about factors driving selection of winter habitat, especially temperature. To illustrate this change, we review three hypotheses seeking to explain microclimate selection in cavernicolous bats. The first, which we call the “Colder is Better Hypothesis,” posits that bats should select cold microclimates that minimize energy expenditure. The “Hibernation Optimization Hypothesis” suggests that bats should select microclimates that reduce expression of torpor to balance energy conservation against non-energetic costs of hibernation. Finally, the “Thrifty Female Hypothesis” asserts that females should select colder microclimates than males to conserve energy for reproduction. We discuss these hypotheses and the shift from viewing hibernation as a phenomenon driven solely by the need to conserve energy in the context of hibernacula management in North America. We focus on both historical and recent conservation threats, most notably alteration of thermal regimes and the disease white-nose syndrome. We urge against returning to an over-simplified view of winter habitat selection in response to our current conservation challenges.Peer reviewe

Atypical audiovisual speech integration in infants at risk for autism

The language difficulties often seen in individuals with autism might stem from an inability to integrate audiovisual information, a skill important for language development. We investigated whether 9-month-old siblings of older children with autism, who are at an increased risk of developing autism, are able to integrate audiovisual speech cues. We used an eye-tracker to record where infants looked when shown a screen displaying two faces of the same model, where one face is articulating/ba/and the other/ga/, with one face congruent with the syllable sound being presented simultaneously, the other face incongruent. This method was successful in showing that infants at low risk can integrate audiovisual speech: they looked for the same amount of time at the mouths in both the fusible visual/ga/− audio/ba/and the congruent visual/ba/− audio/ba/displays, indicating that the auditory and visual streams fuse into a McGurk-type of syllabic percept in the incongruent condition. It also showed that low-risk infants could perceive a mismatch between auditory and visual cues: they looked longer at the mouth in the mismatched, non-fusible visual/ba/− audio/ga/display compared with the congruent visual/ga/− audio/ga/display, demonstrating that they perceive an uncommon, and therefore interesting, speech-like percept when looking at the incongruent mouth (repeated ANOVA: displays x fusion/mismatch conditions interaction: F(1,16) = 17.153, p = 0.001). The looking behaviour of high-risk infants did not differ according to the type of display, suggesting difficulties in matching auditory and visual information (repeated ANOVA, displays x conditions interaction: F(1,25) = 0.09, p = 0.767), in contrast to low-risk infants (repeated ANOVA: displays x conditions x low/high-risk groups interaction: F(1,41) = 4.466, p = 0.041). In some cases this reduced ability might lead to the poor communication skills characteristic of autism

A MIQE-Compliant Real-Time PCR Assay for Aspergillus Detection

PMCID: PMC3393739This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Climate change promotes parasitism in a coral symbiosis.

Coastal oceans are increasingly eutrophic, warm and acidic through the addition of anthropogenic nitrogen and carbon, respectively. Among the most sensitive taxa to these changes are scleractinian corals, which engineer the most biodiverse ecosystems on Earth. Corals' sensitivity is a consequence of their evolutionary investment in symbiosis with the dinoflagellate alga, Symbiodinium. Together, the coral holobiont has dominated oligotrophic tropical marine habitats. However, warming destabilizes this association and reduces coral fitness. It has been theorized that, when reefs become warm and eutrophic, mutualistic Symbiodinium sequester more resources for their own growth, thus parasitizing their hosts of nutrition. Here, we tested the hypothesis that sub-bleaching temperature and excess nitrogen promotes symbiont parasitism by measuring respiration (costs) and the assimilation and translocation of both carbon (energy) and nitrogen (growth; both benefits) within Orbicella faveolata hosting one of two Symbiodinium phylotypes using a dual stable isotope tracer incubation at ambient (26 °C) and sub-bleaching (31 °C) temperatures under elevated nitrate. Warming to 31 °C reduced holobiont net primary productivity (NPP) by 60% due to increased respiration which decreased host %carbon by 15% with no apparent cost to the symbiont. Concurrently, Symbiodinium carbon and nitrogen assimilation increased by 14 and 32%, respectively while increasing their mitotic index by 15%, whereas hosts did not gain a proportional increase in translocated photosynthates. We conclude that the disparity in benefits and costs to both partners is evidence of symbiont parasitism in the coral symbiosis and has major implications for the resilience of coral reefs under threat of global change

Characterizing the pathotype of neonatal meningitis causing <i>Escherichia coli</i> (NMEC)

Background Neonatal meningitis-causing Escherichia coli (NMEC) is the predominant Gram-negative bacterial pathogen associated with meningitis in newborn infants. High levels of heterogeneity and diversity have been observed in the repertoire of virulence traits and other characteristics among strains of NMEC making it difficult to define the NMEC pathotype. The objective of the present study was to identify genotypic and phenotypic characteristics of NMEC that can be used to distinguish them from commensal E. coli. Methods A total of 53 isolates of NMEC obtained from neonates with meningitis and 48 isolates of fecal E. coli obtained from healthy individuals (HFEC) were comparatively evaluated using five phenotypic (serotyping, serum bactericidal assay, biofilm assay, antimicorbial susceptibility testing, and in vitro cell invasion assay) and three genotypic (phylogrouping, virulence genotyping, and pulsed-field gel electrophoresis) methods. Results A majority (67.92 %) of NMEC belonged to B2 phylogenetic group whereas 59 % of HFEC belonged to groups A and D. Serotyping revealed that the most common O and H types present in NMEC tested were O1 (15 %), O8 (11.3 %), O18 (13.2 %), and H7 (25.3 %). In contrast, none of the HFEC tested belonged to O1 or O18 serogroups. The most common serogroup identified in HFEC was O8 (6.25 %). The virulence genotyping reflected that more than 70 % of NMEC carried kpsII, K1, neuC, iucC, sitA, and vat genes with only less than 27 % of HFEC possessing these genes. All NMEC and 79 % of HFEC tested were able to invade human cerebral microvascular endothelial cells. No statistically significant difference was observed in the serum resistance phenotype between NMEC and HFEC. The NMEC strains demonstrated a greater ability to form biofilms in Luria Bertani broth medium than did HFEC (79.2 % vs 39.9 %). Conclusion The results of our study demonstrated that virulence genotyping and phylogrouping may assist in defining the potential NMEC pathotype