Pathways to ensure universal and affordable access to hepatitis C treatment

Direct-acting antivirals (DAAs) have dramatically changed the landscape of hepatitis C treatment and prevention. The World Health Organization has called for the elimination of hepatitis C as a public health threat by 2030. However, the discrepancy in DAA prices across low-, middle- and high-income countries is considerable, ranging from less than US$100 to approximately US$ 40,000 per course, thus representing a major barrier for the scale-up of treatment and elimination. This article describes DAA pricing and pathways to accessing affordable treatment, providing case studies from Australia, Egypt and Portugal. Pathways to accessing DAAs include developing comprehensive viral hepatitis plans to facilitate price negotiations, voluntary and compulsory licenses, patent opposition, joint procurement, and personal importation schemes. While multiple factors influence the price of DAAs, a key driver is a country's capacity and willingness to negotiate with pharmaceutical companies. If negotiations do not lead to a reasonable price, governments have the option to utilise flexibilities outlined in the Agreement on Trade-Related Aspects of Intellectual Property Rights. Affordable access to DAAs is underpinned by collaboration between government, civil society, global organisations and pharmaceutical companies to ensure that all patients can access treatment. Promoting these pathways is critical for influencing policy, improving access to affordable DAAs and achieving hepatitis C elimination

Association of cesarean delivery and formula supplementation with the intestinal microbiome of 6-week-old infants

Author Posting. © American Medical Association, 2016. This article is posted here by permission of American Medical Association for personal use, not for redistribution. The definitive version was published in JAMA Pediatrics 170 (2016): 212-219, doi:10.1001/jamapediatrics.2015.3732.The intestinal microbiome plays a critical role in infant development, and delivery mode and feeding method (breast milk vs formula) are determinants of its composition. However, the importance of delivery mode beyond the first days of life is unknown, and studies of associations between infant feeding and microbiome composition have been generally limited to comparisons between exclusively breastfed and formula-fed infants, with little consideration given to combination feeding of both breast milk and formula.This work was supported in part by grants from the National Institutes of Health (grants NIEHS P01ES022832, NIEHS P20ES018175, NIGMS P20GM104416, NLM K01LM011985, NLM R01LM009012, and NLM R01 LM010098) and the US Environmental Protection Agency (grants RD83459901 and RD83544201).2017-01-1

Social Change and Betty Friedan's The Feminine Mystique: A Study of the Charismatic Author-Leader

In this thesis I explore the significance of the publication of Betty Friedan's The Feminine Mystique (1963) to the emergence of the second wave Women's Liberation Movement in the US in the late 1960s. To this end, I deploy key concepts provided through social movement theory (eg collective identity, collective action frames, social problem construction). I also incorporate Max Weber and Antonio Gramsci's insights on the indispensable role played by leaders who demonstrate a clear and effective political will. Weber's three part model of pure charisma is used as a general template for understanding the impact of Friedan's text. I critique aspects of Weber's theory of charisma, in particular his failure to appreciate that the written word can mark the initial emergence phase of charisma rather than its routinisation. I augment Weber's insights on charismatic leadership by attending to Gramsci's emphasis on the necessity of winning the 'war of ideas' that must be waged at the level of civil society within advanced capitalist societies. I examine Gramsci's understanding of the power available to the organic intellectual who is aligned with the interests of subaltern groups and who succeeds in revealing the hegemonic commitments of accepted 'common sense'. In the latter part of this thesis, I apply these many useful concepts to my case study analysis of Betty Friedan's The Feminine Mystique. I argue that Friedan's accessible, middlebrow text gave birth to a new discursive politics which was critically important not only for older women, but for a younger generation of more radicalised women. I emphasise how Friedan's text mounted a concerted attack on the discursive construction of femininity under patriarchal capitalism. I question Friedan's diagnostic claim that the problems American women faced were adequately captured by the terminology of the trapped housewife syndrome. I conclude by arguing that social movement researchers have to date failed to appreciate the leadership potential of the charismatic author-leader who succeeds in addressing and offering a solution to a pressing social problem through the medium of a best-selling, middlebrow text

Mapping polyclonal antibody responses to bacterial infection using next generation phage display

Mapping polyclonal antibody responses to infectious diseases to identify individual epitopes has the potential to underpin the development of novel serological assays and vaccines. Here, phage-peptide library panning coupled with screening using next generation sequencing was used to map antibody responses to bacterial infections. In the first instance, pigs experimentally infected with Salmonella enterica serovar Typhimurium was investigated. IgG samples from twelve infected pigs were probed in parallel and phage binding compared to that with equivalent IgG from pre-infected animals. Seventy- seven peptide mimotopes were enriched specifically against sera from multiple infected animals. Twenty-seven of these peptides were tested in ELISA and twenty-two were highly discriminatory for sera taken from pigs post-infection (P < 0.05) indicating that these peptides are mimicking epitopes from the bacteria. In order to further test this methodology, it was applied to differentiate antibody responses in poultry to infections with distinct serovars of Salmonella enterica. Twenty-seven peptides were identified as being enriched specifically against IgY from multiple animals infected with S. Enteritidis compared to those infected with S. Hadar. Nine of fifteen peptides tested in ELISA were highly discriminatory for IgY following S. Enteritidis infection (p < 0.05) compared to infections with S. Hadar or S. Typhimurium

Demand for environmentally friendly vehicles: A review and new evidence

Although the need for more environmentally friendly vehicles was recognized some decades ago, this new market has not yet established itself. Consumer behavior needs to be studied to ascertain when people will decide to purchase hybrid or electric vehicles rather than conventional ones. An in-depth review of the state-of-the-art has identified existing deficiencies and these are addressed in this paper, proposing a new approach that is applied to the case of Santander in Spain. Emphasis is placed on the role of citizens in researching the local market and their requirements with respect to such vehicles; our model assumes variability in user preferences, an utmost requirement as concluded from the literature review. Results suggest that the highest demand for cleaner vehicles would be achieved in two ways: firstly, by penalizing conventional vehicles in terms of costs/km; secondly, by providing incentives directed at lowering the purchasing price of hybrid and electric vehicles. Finally, as demand becomes more elastic, the preferred strategy should initially focus on hybrid vehicles

Computational approaches for network-based integrative multi-omics analysis

Advances in omics technologies allow for holistic studies into biological systems. These studies rely on integrative data analysis techniques to obtain a comprehensive view of the dynamics of cellular processes, and molecular mechanisms. Network-based integrative approaches have revolutionized multi-omics analysis by providing the framework to represent interactions between multiple different omics-layers in a graph, which may faithfully reflect the molecular wiring in a cell. Here we review network-based multi-omics/multi-modal integrative analytical approaches. We classify these approaches according to the type of omics data supported, the methods and/or algorithms implemented, their node and/or edge weighting components, and their ability to identify key nodes and subnetworks. We show how these approaches can be used to identify biomarkers, disease subtypes, crosstalk, causality, and molecular drivers of physiological and pathological mechanisms. We provide insight into the most appropriate methods and tools for research questions as showcased around the aetiology and treatment of COVID-19 that can be informed by multi-omics data integration. We conclude with an overview of challenges associated with multi-omics network-based analysis, such as reproducibility, heterogeneity, (biological) interpretability of the results, and we highlight some future directions for network-based integration

Special considerations for studies of extracellular vesicles from parasitic helminths: a community-led roadmap to increase rigour and reproducibility

Over the last decade, research interest in defining how extracellular vesicles (EVs) shape cross-species communication has grown rapidly. Parasitic helminths, worm species found in the phyla Nematoda and Platyhelminthes, are well-recognised manipulators of host immune function and physiology. Emerging evidence supports a role for helminth-derived EVs in these processes and highlights EVs as an important participant in cross-phylum communication. While the mammalian EV field is guided by a community-agreed framework for studying EVs derived from model organisms or cell systems [e.g., Minimal Information for Studies of Extracellular Vesicles (MISEV)], the helminth community requires a supplementary set of principles due to the additional challenges that accompany working with such divergent organisms. These challenges include, but are not limited to, generating sufficient quantities of EVs for descriptive or functional studies, defining pan-helminth EV markers, genetically modifying these organisms, and identifying rigorous methodologies for in vitro and in vivo studies. Here, we outline best practices for those investigating the biology of helminth-derived EVs to complement the MISEV guidelines. We summarise community-agreed standards for studying EVs derived from this broad set of non-model organisms, raise awareness of issues associated with helminth EVs and provide future perspectives for how progress in the field will be achieved