Independent stratum formation on the avian sex chromosomes reveals inter-chromosomal gene conversion and predominance of purifying selection on the w chromosome

We used a comparative approach spanning three species and 90 million years to study the evolutionary history of the avian sex chromosomes. Using whole transcriptomes, we assembled the largest cross-species dataset of W-linked coding content to date. Our results show that recombination suppression in large portions of the avian sex chromosomes has evolved independently, and that long-term sex chromosome divergence is consistent with repeated and independent inversions spreading progressively to restrict recombination. In contrast, over short-term periods we observe heterogeneous and locus-specific divergence. We also uncover four instances of gene conversion between both highly diverged and recently evolved gametologs, suggesting a complex mosaic of recombination suppression across the sex chromosomes. Lastly, evidence from 16 gametologs reveal that the W chromosome is evolving with a significant contribution of purifying selection, consistent with previous findings that W-linked genes play an important role in encoding sex-specific fitness

Strategic advertising of online news articles as an intervention to influence wildlife product consumers

Changing human behavior is essential for biodiversity conservation, but robust approaches for large scale change are needed. Concepts like repeat message exposure and social reinforcement, as well as mechanisms like online news coverage and targeted advertisements, are currently used by private and public sectors, and could prove powerful for conservation. Thus, to explore their potential in influencing wildlife consumption, we used online advertisements through Facebook, Google, and Outbrain, to promote news articles discussing the use of a Critically Endangered antelope (the Saiga tatarica) as a traditional Chinese medicine in Singapore. Our message, tailored to middle-aged Chinese Singaporean women, framed saiga horn products as being no longer socially endorsed. Through advert performance and in-depth analyses of Facebook user engagement, we assessed audience response. Our message pervaded Singapore's online media (e.g., our adverts were shown almost five million times; and the story ran on seven news outlets), and resulted in widespread desirable audience responses (e.g., 63% of Facebook users' engagements included identifiably positive features like calls for public action to reduce saiga horn consumption, anger at having unknowingly used a Critically Endangered species, and self-pledges to no longer use it; only 13% of engagements included identifiably negative features). This work shows that targeted dissemination of online news articles can have promising results, and may have wide applicability to conservation

Organisational response to the 2007 Ruapehu Crater Lake breakout lahar in New Zealand: Use of communication in creating an effective response

When Mt. Ruapehu erupted in 1995-1996 in New Zealand, a tephra barrier was created alongside Crater Lake on the top of Mt. Ruapehu. This barrier acted as a dam, with Crater Lake rising behind it over time. In 2007 the lake breached the dam and a lahar occurred down the Whangaehu Valley and across the volcano’s broad alluvial ring-plain. Given the lahar history from Ruapehu, the risk from the 2007 event was identified beforehand and steps taken to reduce the risks to life and infrastructure. An early warning system was set up to notify when the dam had broken and the lahar had occurred. Physical works to mitigate the risk were put in place. A planning group was also formed and emergency management plans were put in place to respond to the risk. To assess the effectiveness of planning for and responding to the lahar, semi-structured interviews were undertaken with personnel from key organisations both before and after the lahar event. This chapter discusses the findings from the interviews in the context of communications, and highlights how good communications contributed to an effective emergency management response. As the potential for a lahar was identifiable, approximately 10 years of lead-up time was available to install warning system hardware, implement physical mitigation measures, create emergency management plans, and practice exercises for the lahar. The planning and exercising developed effective internal communications, engendered relationships, and moved individuals towards a shared mental model of how a respond to the event. Consequently, the response played out largely as planned with only minor communication issues occurring on the day of the lahar. The minor communication issues were due to strong personal connections leading to at least one case of the plan being bypassed. Communication levels during the lahar event itself were also different from that experienced in exercises, and in some instances communications were seen to increase almost three-fold. This increase in level of communication, led to some difficulty in getting through to the main Incident Control Point. A final thought regarding public communications prior to the event was that more effort could have been given to developing and integrating public information about the lahar, to allow for ease of understanding about the event and integration of information across agencies.falseSubmitte

Development and refinement of a complex intervention within cardiac rehabilitation services: experiences from the CADENCE feasibility study

Published onlineThis is the final version of the article. Available from BioMed Central via the DOI in this record.Background Patients who experience a cardiac event are at higher risk of developing depression than the general population. Despite this, cardiac rehabilitation (CR) programmes do not provide a systematic approach to psychological care for depression. The CADENCE study aimed to develop and pilot an enhanced psychological care (EPC) intervention consisting of behavioural activation (BA) and mental health care coordination. Following original research commissioning guidance, the intervention was planned to be embedded in routine care and delivered by CR nurses to patients with depression attending CR. This paper describes how qualitative methods were used to develop, embed and refine the intervention. Methods This feasibility study involved three CR teams. Observations were made of CR nurses delivering usual care, of EPC training given to nurses, and of supervision sessions provided to the CR nurses. Four nurses were interviewed shortly after their EPC training, and three were interviewed again 6–7 months later having delivered EPC to patients. All nine patients recruited to receive EPC were interviewed. Analyses of the observation notes and interview transcripts focused on how the intervention could be improved in terms of its acceptability and implementation. Results Variations were found between the CR teams regarding patient waiting list times, how CR was delivered, what facilities were available and how many CR sessions were offered to patients. EPC was acceptable to both nurses and patients. However, nurses struggled to provide this additional care within their existing workload and resources, and patients’ disrupted progression through the CR programme affected EPC delivery. Limited time and availability of private space meant nurses also delivered EPC by telephone, which was viewed as a pragmatic solution but less preferable than face-to-face. Nurses indicated that patients struggled with some of the written materials. Findings were used to revise the intervention to become a protocol of care coordination which included guided self-help BA. Conclusions Insights gained through conducting interviews and observations enabled us to identify barriers to the implementation of EPC, and to modify the intervention to facilitate its delivery within existing services whilst remaining acceptable to both nurses and patients. The multiple method, iterative approach used was key to the success of this qualitative study.This project was funded by the UK NIHR Health Technology Assessment Programme (project number 12/189/06) and the over-arching study, including qualitative methods and a pilot trial, is registered with the ISRCTN (ISRCTN34701576; registered 29/05/2014). The Royal Devon & Exeter NHS Foundation Trust is acting as trial sponsor. The Funding Agency and Trial sponsors have not been substantively involved in the design, or data acquisition for this research, nor the drafting of this manuscript; the views and opinions expressed in this paper are those of the authors and do not necessarily reflect those of the Health Technology Assessment Programme, NIHR, NHS or the Department of Health. JC, CD, DAR and SHR are centrally funded by the University of Exeter Medical School. KT is funded by the University of Bristol and her time is supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care West (CLAHRC West) at University Hospitals Bristol NHS Foundation Trust. MG is funded by the Royal Devon & Exeter NHS Foundation Trust. RW and CW were previously employed on the above funding award. DAR and CD are also supported by the NIHR Collaboration for Leadership in Applied Health Research and Care South West Peninsula, and additionally CD is funded by Devon Partnership Trust

Changes in Regional Ventilation During Treatment and Dosimetric Advantages of CT Ventilation Image Guided Radiation Therapy for Locally Advanced Lung Cancer

PURPOSE: Lung functional image guided radiation therapy (RT) that avoids irradiating highly functional regions has potential to reduce pulmonary toxicity following RT. Tumor regression during RT is common, leading to recovery of lung function. We hypothesized that computed tomography (CT) ventilation image-guided treatment planning reduces the functional lung dose compared to standard anatomic image-guided planning in 2 different scenarios with or without plan adaptation. METHODS AND MATERIALS: CT scans were acquired before RT and during RT at 2 time points (16-20 Gy and 30-34 Gy) for 14 patients with locally advanced lung cancer. Ventilation images were calculated by deformable image registration of four-dimensional CT image data sets and image analysis. We created 4 treatment plans at each time point for each patient: functional adapted, anatomic adapted, functional unadapted, and anatomic unadapted plans. Adaptation was performed at 2 time points. Deformable image registration was used for accumulating dose and calculating a composite of dose-weighted ventilation used to quantify the lung accumulated dose-function metrics. The functional plans were compared with the anatomic plans for each scenario separately to investigate the hypothesis at a significance level of 0.05. RESULTS: Tumor volume was significantly reduced by 20% after 16 to 20 Gy (P = .02) and by 32% after 30 to 34 Gy (P < .01) on average. In both scenarios, the lung accumulated dose-function metrics were significantly lower in the functional plans than in the anatomic plans without compromising target volume coverage and adherence to constraints to critical structures. For example, functional planning significantly reduced the functional mean lung dose by 5.0% (P < .01) compared to anatomic planning in the adapted scenario and by 3.6% (P = .03) in the unadapted scenario. CONCLUSIONS: This study demonstrated significant reductions in the accumulated dose to the functional lung with CT ventilation image-guided planning compared to anatomic image-guided planning for patients showing tumor regression and changes in regional ventilation during RT

Mycobacterial infection-induced miR-206 inhibits protective neutrophil recruitment via the CXCL12/CXCR4 signalling axis

Pathogenic mycobacteria actively dysregulate protective host immune signalling pathways during infection to drive the formation of permissive granuloma microenvironments. Dynamic regulation of host microRNA (miRNA) expression is a conserved feature of mycobacterial infections across host-pathogen pairings. Here we examine the role of miR-206 in the zebrafish model of Mycobacterium marinum infection, which allows investigation of the early stages of granuloma formation. We find miR-206 is upregulated following infection by pathogenic M. marinum and that antagomir-mediated knockdown of miR-206 is protective against infection. We observed striking upregulation of cxcl12a and cxcr4b in infected miR-206 knockdown zebrafish embryos and live imaging revealed enhanced recruitment of neutrophils to sites of infection. We used CRISPR/Cas9-mediated knockdown of cxcl12a and cxcr4b expression and AMD3100 inhibition of Cxcr4 to show that the enhanced neutrophil response and reduced bacterial burden caused by miR-206 knockdown was dependent on the Cxcl12/Cxcr4 signalling axis. Together, our data illustrate a pathway through which pathogenic mycobacteria induce host miR-206 expression to suppress Cxcl12/Cxcr4 signalling and prevent protective neutrophil recruitment to granulomas

Evaluation of Xpert® MTB/RIF and ustar easyNAT™ TB IAD for diagnosis of tuberculous lymphadenitis of children in Tanzania : a prospective descriptive study

Fine needle aspiration biopsy has become a standard approach for diagnosis of peripheral tuberculous lymphadenitis. The aim of this study was to compare the performance of Xpert MTB/RIF and Ustar EasyNAT TB IAD nucleic acid amplification assays, against acid-fast bacilli microscopy, cytology and mycobacterial culture for the diagnosis of TB lymphadenitis in children from a TB-endemic setting in Tanzania.; Children of 8 weeks to 16 years of age, suspected of having TB lymphadenitis, were recruited at a district hospital in Tanzania. Fine needle aspirates of lymph nodes were analysed using acid-fast bacilli microscopy, liquid TB culture, cytology, Xpert MTB/RIF and EasyNAT. Latent class analysis and comparison against a composite reference standard comprising "culture and/or cytology" was done, to assess the performance of Xpert MTB/RIF and EasyNAT for the diagnosis of TB lymphadenitis.; Seventy-nine children were recruited; 4 were excluded from analysis. Against a composite reference standard of culture and/or cytology, Xpert MTB/RIF and EasyNAT had a sensitivity and specificity of 58 % and 93 %; and 19 % and 100 % respectively. Relative to latent class definitions, cytology had a sensitivity of 100 % and specificity of 94.7 %.; Combining clinical assessment, cytology and Xpert MTB/RIF may allow for a rapid and accurate diagnosis of childhood TB lymphadenitis. Larger diagnostic evaluation studies are recommended to validate these findings and on Xpert MTB/RIF to assess its use as a solitary initial test for TB lymphadenitis in children

Antralization at the edge of proximal gastric ulcers: Does Helicobacter pylori infection play a role?

Aim: To determine the prevalence of antralization at the edge of proximal gastric ulcers, and the effect of H. pylori eradication on the mucosal appearances. Methods: Biopsies were taken from the antrum, body and the ulcer edge of patients with benign proximal gastric ulcers before and one year after treatment. Gastric mucosa was classified as antral, transitional or body type. H. pylori positive patients received either triple therapy, or omeprazole. Results: Patients with index ulcers in the incisura, body or fundus (n=116) were analyzed. Antral-type mucosa was more prevalent at the ulcer edge in H. pylori-positive patients than H. pylori-negative patients (93 % vs 60 %, OR=8.95, 95 %CI: 2.47-32.4, P=0.001). At one year, there was a significant reduction in the prevalence of antralization (from 93 % to 61 %, P=0.004) at the ulcer edge in patients with H. pylori being eradicated. However, there was no difference in the prevalence of antralization at the ulcer edge in those with persistent infection. Conclusion: H. pylori infection is associated with antralization at the edge of proximal gastric ulcers, which may be reversible in some patients after eradication of the infection.published_or_final_versio

‘Warning: allergic to penicillin’: association between penicillin allergy status in 2.3 million NHS general practice electronic health records, antibiotic prescribing and health outcomes

Background The prevalence of reported penicillin allergy (PenA) and the impact these records have on health outcomes in the UK general population are unknown. Without such data, justifying and planning enhanced allergy services is challenging. Objectives To determine: (i) prevalence of PenA records; (ii) patient characteristics associated with PenA records; and (iii) impact of PenA records on antibiotic prescribing/health outcomes in primary care. Methods We carried out cross-sectional/retrospective cohort studies using patient-level data from electronic health records. Cohort study: exact matching across confounders identified as affecting PenA records. Setting: English NHS general practices between 1 April 2013 and 31 March 2014. Participants: 2.3 million adult patients. Outcome measures: prevalence of PenA, antibiotic prescribing, mortality, MRSA infection/colonization and Clostridioides difficile infection. Results PenA prevalence was 5.9% (IQR = 3.8%–8.2%). PenA records were more common in older people, females and those with a comorbidity, and were affected by GP practice. Antibiotic prescribing varied significantly: penicillins were prescribed less frequently in those with a PenA record [relative risk (RR)  = 0.15], and macrolides (RR = 4.03), tetracyclines (RR = 1.91) nitrofurantoin (RR = 1.09), trimethoprim (RR = 1.04), cephalosporins (RR = 2.05), quinolones (RR = 2.10), clindamycin (RR = 5.47) and total number of prescriptions were increased in patients with a PenA record. Risk of re-prescription of a new antibiotic class within 28 days (RR = 1.32), MRSA infection/colonization (RR = 1.90) and death during the year subsequent to 1 April 2013 (RR = 1.08) increased in those with PenA records. Conclusions PenA records are common in the general population and associated with increased/altered antibiotic prescribing and worse health outcomes. We estimate that incorrect PenA records affect 2.7 million people in England. Establishing true PenA status (e.g. oral challenge testing) would allow more people to be prescribed first-line antibiotics, potentially improving health outcomes

OXSR1 inhibits inflammasome activation by limiting potassium efflux during mycobacterial infection.

Pathogenic mycobacteria inhibit inflammasome activation to establish infection. Although it is known that potassium efflux is a trigger for inflammasome activation, the interaction between mycobacterial infection, potassium efflux, and inflammasome activation has not been investigated. Here, we use Mycobacterium marinum infection of zebrafish embryos and Mycobacterium tuberculosis infection of THP-1 cells to demonstrate that pathogenic mycobacteria up-regulate the host WNK signalling pathway kinases SPAK and OXSR1 which control intracellular potassium balance. We show that genetic depletion or inhibition of OXSR1 decreases bacterial burden and intracellular potassium levels. The protective effects of OXSR1 depletion are at least partially mediated by NLRP3 inflammasome activation, caspase-mediated release of IL-1β, and downstream activation of protective TNF-α. The elucidation of this druggable pathway to potentiate inflammasome activation provides a new avenue for the development of host-directed therapies against intracellular infections