Henipavirus zoonosis: outbreaks, animal hosts and potential new emergence

Hendra virus (HeV) and Nipah virus (NiV) are biosafety level 4 zoonotic pathogens causing severe and often fatal neurological and respiratory disease. These agents have been recognized by the World Health Organization as top priority pathogens expected to result in severe future outbreaks. HeV has caused sporadic infections in horses and a small number of human cases in Australia since 1994. The NiV Malaysia genotype (NiV-M) was responsible for the 1998–1999 epizootic outbreak in pigs with spillover to humans in Malaysia and Singapore. Since 2001, the NiV Bangladesh genotype (NiV-B) has been the predominant strain leading to outbreaks almost every year in Bangladesh and India, with hundreds of infections in humans. The natural reservoir hosts of HeV and NiV are fruit bats, which carry the viruses without clinical manifestation. The transmission pathways of henipaviruses from bats to humans remain poorly understood. Transmissions are often bridged by an intermediate animal host, which amplifies and spreads the viruses to humans. Horses and pigs are known intermediate hosts for the HeV outbreaks in Australia and NiV-M epidemic in Malaysia and Singapore, respectively. During the NiV-B outbreaks in Bangladesh, following initial spillover thought to be through the consumption of date palm sap, the spread of infection was largely human-to-human transmission. Spillover of NiV-B in recent outbreaks in India is less understood, with the primary route of transmission from bat reservoir to the initial human infection case(s) unknown and no intermediate host established. This review aims to provide a concise update on the epidemiology of henipaviruses covering their previous and current outbreaks with emphasis on the known and potential role of livestock as intermediate hosts in disease transmission. Also included is an up-to-date summary of newly emerging henipa-like viruses and animal hosts. In these contexts we discuss knowledge gaps and new challenges in the field and propose potential future directions

Sublingual Adjuvant Delivery by a Live Attenuated Vibrio cholerae-Based Antigen Presentation Platform

ABSTRACT A sublingually delivered heterologous antigen presentation platform that does not depend on antigen or adjuvant purification would be of great benefit in protection against diarrheal disease. In proof-of-concept studies, we previously showed that when a fusion protein comprised of the Vibrio cholerae biofilm matrix protein RbmA and the B subunit of cholera toxin (R-CTB) is expressed from a plasmid within V. cholerae, R-CTB is sequestered in the biofilm matrix, leading to decoration of the cell surface. Sublingual delivery of live attenuated R-CTB-decorated cells results in a mucosal immune response to CTB. To improve the immune response to diarrheal antigens presented by this platform, we have engineered our live attenuated vaccine to express the mucosal adjuvant mmCT (i.e., multiply mutated CT). Here we report that delivery of this adjuvant via sublingual administration of our vaccine enhances the mucosal immune response to V. cholerae LPS and elicits a systemic and mucosal immune response to CTB. However, provision of R-CTB with mmCT selectively blunts the mucosal immune response to CTB. We propose that mmCT delivered by this live attenuated Vibrio cholerae vaccine platform may serve as a mucosal adjuvant for heterologous antigens, provided they are not too similar to mmCT. IMPORTANCE: Diarrheal disease is the most common infectious disease of children in the developing world. Our goal is to develop a diarrheal antigen presentation platform based on whole Vibrio cholerae cells that does not depend on protein purification. We have previously shown the feasibility of genetically fusing antigens to the V. cholerae biofilm matrix protein RbmA for presentation on the cell surface. A mucosal adjuvant could improve immunogenicity of such a vaccine at the mucosal surface. Here we engineer a live attenuated V. cholerae vaccine to constitutively synthesize mmCT, a nontoxic form of cholera toxin. When this vaccine is delivered sublingually, in vivo-synthesized mmCT acts as both an adjuvant and antigen. This could greatly increase the magnitude and duration of the immune response elicited by codelivered heterologous antigens

Just a wind-up? Ethnicity, religion and prejudice in Scottish football-related comedy

This article probes how media representations of football in Scotland sustain the hegemonic ideologies associated with ethnicity and religion. The paper probes the football-related comedy output of one radio programme; radio output and football comedy are both neglected cultural material in studies of sport in Scotland. It argues that ambiguity and allusive language in comedy construct multiple interpretative possibilities that can demean the social and cultural identity of particular groups in society. The discussion analyses specific sketches from the Scottish radio comedy show Watson's Wind Up. It is concluded that although humorous, these sketches reveal how ideas, myths and stereotypes that coalesce round Celtic FC and the Irish-descended and Catholic communities in Scotland reinforce and sustain anti-Irish and anti-Catholic bigotry

The implications of three major new trials for the effect of water, sanitation and hygiene on childhood diarrhea and stunting: a consensus statement

BACKGROUND: Three large new trials of unprecedented scale and cost, which included novel factorial designs, have found no effect of basic water, sanitation and hygiene (WASH) interventions on childhood stunting, and only mixed effects on childhood diarrhea. Arriving at the inception of the United Nations' Sustainable Development Goals, and the bold new target of safely managed water, sanitation and hygiene for all by 2030, these results warrant the attention of researchers, policy-makers and practitioners. MAIN BODY: Here we report the conclusions of an expert meeting convened by the World Health Organization and the Bill and Melinda Gates Foundation to discuss these findings, and present five key consensus messages as a basis for wider discussion and debate in the WASH and nutrition sectors. We judge these trials to have high internal validity, constituting good evidence that these specific interventions had no effect on childhood linear growth, and mixed effects on childhood diarrhea. These results suggest that, in settings such as these, more comprehensive or ambitious WASH interventions may be needed to achieve a major impact on child health. CONCLUSION: These results are important because such basic interventions are often deployed in low-income rural settings with the expectation of improving child health, although this is rarely the sole justification. Our view is that these three new trials do not show that WASH in general cannot influence child linear growth, but they do demonstrate that these specific interventions had no influence in settings where stunting remains an important public health challenge. We support a call for transformative WASH, in so much as it encapsulates the guiding principle that - in any context - a comprehensive package of WASH interventions is needed that is tailored to address the local exposure landscape and enteric disease burden

Expression of androgen receptor splice variants in clinical breast cancers

Published: November 05, 2015The importance of androgen receptor (AR) signaling is increasingly being recognized in breast cancer, which has elicited clinical trials aimed at assessing the efficacy of androgen deprivation therapy (ADT) for metastatic disease. In prostate cancer, resistance to ADT is frequently associated with the emergence of androgen-independent splice variants of the AR (AR variants, AR-Vs) that lack the LBD and are constitutively active. Women with breast cancer may be prone to a similar phenomenon. Herein, we show that in addition to the prototypical transcript, the AR gene produces a diverse range of AR-V transcripts in primary breast tumors. The most frequently and highly expressed variant was AR-V7 (exons 1/2/3/CE3), which was detectable at the mRNA level in > 50% of all breast cancers and at the protein level in a subset of ERα-negative tumors. Functionally, AR-V7 is a constitutively active and ADT-resistant transcription factor that promotes growth and regulates a transcriptional program distinct from AR in ERα-negative breast cancer cells. Importantly, we provide ex vivo evidence that AR-V7 is upregulated by the AR antagonist enzalutamide in primary breast tumors. These findings have implications for treatment response in the ongoing clinical trials of ADT in breast cancer.Theresa E. Hickey, Connie M. Irvine, Heidi Dvinge, Gerard A. Tarulli, Adrienne R. Hanson, Natalie K. Ryan, Marie A. Pickering, Stephen N. Birrell, Dong Gui Hu, Peter I. Mackenzie, Roslin Russell, Carlos Caldas, Ganesh V. Raj, Scott M. Dehm, Stephen R. Plymate, Robert K. Bradley, Wayne D. Tilley, Luke A. Selt

The relationship between gambling event frequency, motor response inhibition, arousal, and dissociative experience

Speed of play has been identified as a key structural characteristic in gambling behaviour, where games involving higher playing speeds enhance the experience of gambling. Of interest in the present study is the consistent finding that games with higher event frequencies are preferred by problem gamblers and are associated with more negative gambling outcomes, such as difficulty quitting the game and increased monetary loss. The present study investigated the impact of gambling speed of play on executive control functioning, focusing on how increased speeds of play impact motor response inhibition, and the potential mediating role arousal and dissociative experience play in this relationship. Fifty regular non-problem gamblers took part in a repeated-measures experiment where they gambled with real money on a simulated slot machine across five speed of play conditions. Response inhibition was measured using an embedded Go/No-Go task, where participants had to withhold motor responses, rather than operating the spin button on the slot machine when a specific colour cue was present. Results indicated that response inhibition performance was significantly worse during faster speeds of play, and that the role of arousal in this relationship was independent of any motor priming affect. The implications of these findings for gambling legislation and gambling harm-minimisation approaches are discussed

Active children through individual vouchers – evaluation (ACTIVE): protocol for a mixed method randomised control trial to increase physical activity levels in teenagers

BackgroundMany teenagers are insufficiently active despite the health benefits of physical activity (PA). There is strong evidence to show that inactivity and low fitness levels increase the risk of non-communicable diseases such as coronary heart disease (CHD), type 2 diabetes and breast and colon cancers (Lee et al. Lancet 380:219–29, 2012). A major barrier facing adolescents is accessibility (e.g. cost and lack of local facilities). The ACTIVE project aims to tackle this barrier through a multi-faceted intervention, giving teenagers vouchers to spend on activities of their choice and empowering young people to improve their fitness and PA levels.DesignACTIVE is a mixed methods randomised control trial in 7 secondary schools in Swansea, South Wales. Quantitative and qualitative measures including PA (cooper run test (CRT), accelerometery over 7 days), cardiovascular (CV) measures (blood pressure, pulse wave analysis) and focus groups will be undertaken at 4 separate time points (baseline, 6 months,12 months and follow-up at 18 months). Intervention schools will receive a multi-component intervention involving 12 months of £20 vouchers to spend on physical activities of their choice, a peer mentor scheme and opportunities to attend advocacy meetings. Control schools are encouraged to continue usual practice. The primary aim is to examine the effect of the intervention in improving cardiovascular fitness.DiscussionThis paper describes the protocol for the ACTIVE randomised control trial, which aims to increase fitness, physical activity and socialisation of teenagers in Swansea, UK via a voucher scheme combined with peer mentoring. Results can contribute to the evidence base on teenage physical activity and, if effective, the intervention has the potential to inform future physical activity interventions and policy

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Sex, Gender and Work Segregation in the Cultural Industries

This chapter addresses work ‘segregation’ by sex in the cultural industries. We outline some of the main forms this takes, according to our observations: the high presence of women in marketing and public relations roles; the high numbers of women in production co-ordination and similar roles; the domination of men of more prestigious creative roles; and the domination by men of technical jobs. We then turn to explanation: what gender dynamics drive such patterns of work segregation according to sex? Drawing on interviews, we claim that the following stereotypes or prevailing discourses, concerning the distinctive attributes of women and men, may influence such segregation: that women are more caring, supportive and nurturing; that women are better communicators; that women are ‘better organized’; and that men are more creative because they are less bound by rules

Use of cancer-specific yeast-secreted in vivo biotinylated recombinant antibodies for serum biomarker discovery

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