Correction: Delayed Goblet Cell Hyperplasia, Acetylcholine Receptor Expression, and Worm Expulsion in SMC-Specific IL-4Rα–Deficient Mice

Interleukin 4 receptor alpha (IL-4Ralpha) is essential for effective clearance of gastrointestinal nematode infections. Smooth muscle cells are considered to play a role in the type 2 immune response-driven expulsion of gastrointestinal nematodes. Previous studies have shown in vitro that signal transducer and activator of transcription 6 signaling in response to parasitic nematode infection significantly increases smooth muscle cell contractility. Inhibition of the IL-4Ralpha pathway inhibits this response. How this response manifests itself in vivo is unknown. In this study, smooth muscle cell IL-4Ralpha-deficient mice (SM-MHC(Cre)IL-4Ralpha(-/lox)) were generated and characterized to uncover any role for IL-4/IL-13 in this non-immune cell type in response to Nippostrongylus brasiliensis infection. IL-4Ralpha was absent from alpha-actin-positive smooth muscle cells, while other cell types showed normal IL-4Ralpha expression, thus demonstrating efficient cell-type-specific deletion of the IL-4Ralpha gene. N. brasiliensis-infected SM-MHC(Cre)IL-4Ralpha(-/lox) mice showed delayed ability to resolve infection with significantly prolonged fecal egg recovery and delayed worm expulsion. The delayed expulsion was related to a delayed intestinal goblet cell hyperplasia, reduced T helper 2 cytokine production in the mesenteric lymph node, and reduced M3 muscarinic receptor expression during infection. Together, these results demonstrate that in vivo IL-4Ralpha-responsive smooth muscle cells are beneficial for N. brasiliensis expulsion by coordinating T helper 2 cytokine responses, goblet hyperplasia, and acetylcholine responsiveness, which drive smooth muscle cell contractions

Psychological distress and suicidal ideation in patients with atrial fibrillation: prevalence and response to management strategy

Background: An association between atrial fibrillation ( AF ), anxiety, and depression is recognized, but the spectrum of psychological distress remains unclear. We aimed to characterize the severity and predictors of distress associated with AF in a tertiary population and its response to AF management. Methods and Results: Seventy-eight patients with symptomatic AF underwent evaluation, including of AF symptom severity, health-related quality of life, psychological distress, suicidal ideation, and specific personality traits. Twenty participants underwent AF ablation and 58 were managed medically, with repeat assessments at 4, 8, and 12 months. Severe distress (Hospital Anxiety and Depression Scale score, ≥15/42) was identified in 27 of 78 (35%). Independent predictors were a personality marked by vulnerability to stress (Perceived Stress Scale: R2, 0.54; β=0.7±0.1; t=7.8; P<0.001) and 1 marked by negativity/social inhibition (Type D Personality Scale: R2, 0.47; β=0.7±0.1; t=6.7; P<0.001). Suicidal ideation was reported by 16 of 78 (20%) and was predicted by personality traits (Perceived Stress Scale score: R2, 0.35; odds ratio, 1.22±0.06; P<0.001; Type D Personality Scale score: R2, 0.48; odds ratio, 1.43±0.14; P<0.001). Effective AF ablation (median AF burden 1% [0-1%] over 12 months) was associated with significant reductions in distress (Hospital Anxiety and Depression Scale score, 13.9±1.8 to 4.3±1.8; P<0.05) and prevalence of suicidal ideation (30-5%; P=0.02). Conclusions: There was a high prevalence of severe psychological distress (35%) and of suicidal ideation (20%) in a tertiary AF population, with personality traits predicting both. Effective AF ablation was associated with significant improvements, suggesting AF itself may be a treatable causative factor of distress.Tomos E. Walters, Kate Wick, Gabriel Tan, Megan Mearns, Stephen A. Joseph, Joseph B. Morton, Prashanthan Sanders, Christina Bryant, Peter M. Kistler, Jonathan M. Kalma

A Portuguese East Indiaman from the 1502-1503 Fleet of Vasco da Gama off Al Hallaniyah Island, Oman: An interim report

Two Portuguese naus from Vasco da Gama's second voyage to India, left behind to disrupt maritime trade between India and the Red Sea, were wrecked in May 1503 off the north-eastern coast of Al Hallaniyah Island, Oman. The ships, Esmeralda and São Pedro, had been commanded by da Gama's maternal uncles, Vicente and Brás Sodré, respectively. A detailed study and scientific analysis of an artefact assemblage recovered during archaeological excavations conducted in Al Hallaniyah in 2013 and 2014 confirms the location of an early 16th-century Portuguese wreck-site, initially discovered in 1998. Esmeralda is proposed as the probable source of the remaining, un-salved wreckage

A case for taking the dual role of counsellor-researcher in qualitative research

This is an Accepted Manuscript of an article published by Taylor & Francis in Qualitative Research in Psychology on 3rd August 2016, available online: https://doi.org/10.1080/14780887.2016.1205694There is ongoing debate about whether the challenges of practice-based research in counselling, with clients’ discourses providing the raw data, can be overcome. This article begins by considering the argument of whether taking a dual role of counsellor-researcher within case study research is a legitimate qualitative approach. A case example using sand-tray in short-term therapy with adults from a pluralistic perspective is provided to demonstrate how the challenges of the dual role can be managed to produce effective research findings. It is suggested that this approach closes the gap between research and practice to produce findings that are highly relevant to the counselling context. The ethical considerations of taking a dual role of counsellor-researcher are considered, and opportunities and challenges when adopting this approach are identified

Localisation of gamma-ray bursts from the combined SpIRIT+HERMES-TP/SP nano-satellite constellation

Multi-messenger observations of the transient sky to detect cosmic explosions and counterparts of gravitational wave mergers critically rely on orbiting wide-FoV telescopes to cover the wide range of wavelengths where atmospheric absorption and emission limit the use of ground facilities. Thanks to continuing technological improvements, miniaturised space instruments operating as distributed-aperture constellations are offering new capabilities for the study of high energy transients to complement ageing existing satellites. In this paper we characterise the performance of the upcoming joint SpIRIT + HERMES-TP/SP nano-satellite constellation for the localisation of high-energy transients through triangulation of signal arrival times. SpIRIT is an Australian technology and science demonstrator satellite designed to operate in a low-Earth Sun-synchronous Polar orbit that will augment the science operations for the equatorial HERMES-TP/SP. In this work we simulate the improvement to the localisation capabilities of the HERMES-TP/SP when SpIRIT is included in an orbital plane nearly perpendicular (inclination = 97.6$^\circ$) to the HERMES orbits. For the fraction of GRBs detected by three of the HERMES satellites plus SpIRIT, the combined constellation is capable of localising 60% of long GRBs to within ~ 30 deg$^2$ on the sky, and 60% of short GRBs within ~ 1850 deg$^2$. Based purely on statistical GRB localisation capabilities (i.e., excluding systematic uncertainties and sky coverage), these figures for long GRBs are comparable to those reported by the Fermi GBM. Further improvements by a factor of 2 (or 4) can be achieved by launching an additional 4 (or 6) SpIRIT-like satellites into a Polar orbit, which would both increase the fraction of sky covered by multiple satellite elements, and enable $\geq$ 60% of long GRBs to be localised within a radius of ~ 1.5$^\circ$ on the sky.Comment: 17 pages, 10 figures, 1 table. Accepted for publication in PAS

Delayed Goblet Cell Hyperplasia, Acetylcholine Receptor Expression, and Worm Expulsion in SMC-Specific IL-4Rα–Deficient Mice

Interleukin 4 receptor α (IL-4Rα) is essential for effective clearance of gastrointestinal nematode infections. Smooth muscle cells are considered to play a role in the type 2 immune response–driven expulsion of gastrointestinal nematodes. Previous studies have shown in vitro that signal transducer and activator of transcription 6 signaling in response to parasitic nematode infection significantly increases smooth muscle cell contractility. Inhibition of the IL-4Rα pathway inhibits this response. How this response manifests itself in vivo is unknown. In this study, smooth muscle cell IL-4Rα–deficient mice (SM-MHC(Cre)IL-4Rα(−/lox)) were generated and characterized to uncover any role for IL-4/IL-13 in this non–immune cell type in response to Nippostrongylus brasiliensis infection. IL-4Rα was absent from α-actin–positive smooth muscle cells, while other cell types showed normal IL-4Rα expression, thus demonstrating efficient cell-type–specific deletion of the IL-4Rα gene. N. brasiliensis–infected SM-MHC(Cre)IL-4Rα(−/lox) mice showed delayed ability to resolve infection with significantly prolonged fecal egg recovery and delayed worm expulsion. The delayed expulsion was related to a delayed intestinal goblet cell hyperplasia, reduced T helper 2 cytokine production in the mesenteric lymph node, and reduced M3 muscarinic receptor expression during infection. Together, these results demonstrate that in vivo IL-4Rα–responsive smooth muscle cells are beneficial for N. brasiliensis expulsion by coordinating T helper 2 cytokine responses, goblet hyperplasia, and acetylcholine responsiveness, which drive smooth muscle cell contractions

Nippostrongylus-induced intestinal hypercontractility requires IL-4 receptor alpha-responsiveness by T cells in mice

Gut-dwelling helminthes induce potent IL-4 and IL-13 dominated type 2 T helper cell (T H 2) immune responses, with IL-13 production being essential for Nippostrongylus brasiliensis expulsion. This T H 2 response results in intestinal inflammation associated with local infiltration by T cells and macrophages. The resulting increased IL-4/IL-13 intestinal milieu drives goblet cell hyperplasia, alternative macrophage activation and smooth muscle cell hypercontraction. In this study we investigated how IL-4-promoted T cells contributed to the parasite induced effects in the intestine. This was achieved using pan T cell-specific IL-4 receptor alpha-deficient mice (iLck cre IL-4Rα −/lox ) and IL-4Rα-responsive control mice. Global IL-4Rα −/− mice showed, as expected, impaired type 2 immunity to N. brasiliensis . Infected T cell-specific IL-4Rα-deficient mice showed comparable worm expulsion, goblet cell hyperplasia and IgE responses to control mice. However, impaired IL-4-promoted T H 2 cells in T cell-specific IL-4Rα deficient mice led to strikingly reduced IL-4 production by mesenteric lymph node CD4 + T cells and reduced intestinal IL-4 and IL-13 levels, compared to control mice. This reduced IL-4/IL-13 response was associated with an impaired IL-4/IL-13-mediated smooth muscle cell hypercontractility, similar to that seen in global IL-4Rα −/− mice. These results demonstrate that IL-4-promoted T cell responses are not required for the resolution of a primary N. brasiliensis infection. However, they do contribute significantly to an important physiological manifestation of helminth infection; namely intestinal smooth muscle cell-driven hypercontractility

Fact and fiction in housing research: utilizing the creative imagination

As much of our conceptual framework is informed by the experience of the imagination, there is much to be learnt from a study of various creative forms. Narrative fiction can be one such form, allowing us to gain a useful insight into complex features of social life. The purpose of this article is to investigate the treatment of housing issues in contemporary literature in order to gain insights into attitudes, experiences and interpretations from the perspective of a broad cultural milieu. Discussions of professionalism, housing tenure and homelessness have tended to be conducted within a narrow framework and adopted orthodox modes of evaluation. Consequently, the neglect of housing within a wider cultural context has reinforced the isolation of housing issues. The article argues that although discussions of housing and housing policy have been seriously limited within the contemporary novel, there are a number of key insights that can be gained from a discussion of issues within a fictional setting

Fire as a fundamental ecological process: Research advances and frontiers

Fire is a powerful ecological and evolutionary force that regulates organismal traits, population sizes, species interactions, community composition, carbon and nutrient cycling and ecosystem function. It also presents a rapidly growing societal challenge, due to both increasingly destructive wildfires and fire exclusion in fire‐dependent ecosystems. As an ecological process, fire integrates complex feedbacks among biological, social and geophysical processes, requiring coordination across several fields and scales of study. Here, we describe the diversity of ways in which fire operates as a fundamental ecological and evolutionary process on Earth. We explore research priorities in six categories of fire ecology: (a) characteristics of fire regimes, (b) changing fire regimes, (c) fire effects on above‐ground ecology, (d) fire effects on below‐ground ecology, (e) fire behaviour and (f) fire ecology modelling. We identify three emergent themes: the need to study fire across temporal scales, to assess the mechanisms underlying a variety of ecological feedbacks involving fire and to improve representation of fire in a range of modelling contexts. Synthesis : As fire regimes and our relationships with fire continue to change, prioritizing these research areas will facilitate understanding of the ecological causes and consequences of future fires and rethinking fire management alternatives