Effects of H2-Receptor Antagonists on the Exposure of Dacomitinib.

Dacomitinib is an irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor indicated for the treatment of patients with advanced non-small-cell lung cancer (NSCLC) and EGFR-activating mutations. Proton-pump inhibitors decreased dacomitinib exposure. This analysis summarizes the effect of Histamine-2 receptor antagonists (H2RAs) on dacomitinib exposure. A within-patient comparison of the steady-state trough concentrations (Ctrough,ss) of dacomitinib and its active metabolite and active moiety with and without concomitant use of H2RAs was conducted using a linear mixed effects model with pooled data from 11 clinical studies in patients with NSCLC. An oral absorption physiologically based pharmacokinetic (PBPK) model was constructed and verified using clinical pharmacokinetic (PK) data after a single dose of dacomitinib in healthy volunteers to estimate the effect of gastric pH altered by an H2RA on dacomitinib's PKs. The adjusted geometric mean of the dacomitinib Ctrough,ss of the dacomitinib parent, metabolite and active moiety following co-administration with an H2RA was approximately 86%, 104% and 100% relative to that following dacomitinib 45 mg administration without an H2RA (p > 0.05). The PBPK modeling showed negligible change in dacomitinib maximum concentration (Cmax) and area under the drug concentration-time curve (AUC) over 0-24 h after H2RA administration when compared with those administered dacomitinib alone. Co-administration of an H2RA with dacomitinib is not expected to have any clinically relevant effect on dacomitinib exposure.

Media, nationalism, and the body: Exploring masculinities, male partner violence, and HIV vulnerability among female sex workers in northern Karnataka, India.

Public health and media discourses on men and HIV prevention in India have largely focused on changing knowledge, attitudes and risk behaviour pertaining to condom use and safe sex. Little attempt has been made towards intervening in areas such as masculinity, dominant gender norms and intimate partner violence (IPV) that have been shown to have a direct link to HIV prevalence. In this paper, drawing on findings from an ethnographic study in northern Karnataka (India), we show how socio-political and communicative contexts influence and perpetuate violent behaviours by men in intimate relationships with female sex workers (FSW). We argue that constructions of masculinity, the stereotypes of which are reinforced through contemporary media, and movies, are intricately linked with processes of nationalism and play out in forms of chauvinism among working-class men. Violence, celebrated through various patriarchal discourses, legitimises and reinforces gender ideals that govern the private lives of men and their female intimate partners. This study provides a complex and nuanced understanding of structural factors that lead to IPV against FSWs and offers implications for HIV intervention planning in the region and beyond.

Exploring male adolescents' perceptions of gender relations in South India: A project ethnography of the Parivartan program.

In Northern Karnataka, South India, boys' behaviours and attitudes towards girls are regarded as one of the many important proximate structural barriers impeding girls' access to education and academic performance in rural communities. In response to these barriers, public health practitioners developed an intervention, known as the Parivartan program, to confront the wider social and structural influences that shape adolescent boys' perspectives on gender relationships and practices that subjugate adolescent girls. Drawing upon a project ethnography approach, this study presents the findings from two phases of research conducted between 2014 and 2016 among adolescent boys who participated in the Parivartan program. First, 20 baseline qualitative interviews were conducted among male participants (between the ages 14 and 18) enrolled in the program. Next, follow-up ethnographic research, which included participant observation and ethnographic field note composition, took place one year after commencement of the intervention to illuminate the effects of the program on participants' perspectives. Transcripts and field notes were coded for key themes and emergent categories focused on representing adolescent boys' views and experiences through their narrative accounts. Within the context of an intervention, our findings portray masculinity among participants as simultaneously socially contingent, shifting and still undergoing negotiation, thereby providing an entry point through which program implementers can further encourage boys to transcend patriarchal expectations. Our findings hold important lessons for the design of future HIV and gender-based interventions with adolescent boys in India.

Money boys in Chengdu, China: migration, entrepreneurial precarity and health service access.

This qualitative study highlights the complex interplay between the social and structural conditions in Chengdu, China that shape the possibilities and vulnerabilities of money boys' sexual health. Within the context of China's liberalised market economy, we explore (1) how money boys' enter the sex trade market and navigate their sexual networks; (2) how their lives are enmeshed in fields of sexual desire, stigma and coercion; and (3) how the illicit and stigmatising nature of their work poses barriers to health service access. Findings reveal how the sex trade market and clinic are precarious spaces in which entrepreneurial ethics of the self and stigma-related coercive relations simultaneously enable and constrain money boys' sexual freedom and safer sex practices. By understanding this entrepreneurial precarity through the co-articulation of clinical and organisational work spaces, public health and social service providers can have a stronger sense of how various vulnerabilities configure to affect safer sex practices.

A Novel Genus of Actinobacterial Tectiviridae.

Streptomyces phages WheeHeim and Forthebois are two novel members of the Tectiviridae family. These phages were isolated on cultures of the plant pathogen Streptomyces scabiei, known for its worldwide economic impact on potato crops. Transmission electron microscopy showed viral particles with double-layered icosahedral capsids, and frequent instances of protruding nanotubes harboring a collar-like structure. Mass-spectrometry confirmed the presence of lipids in the virion, and serial purification of colonies from turbid plaques and immunity testing revealed that both phages are temperate. Streptomycesphages WheeHeim and Forthebois have linear dsDNA chromosomes (18,266 bp and 18,251 bp long, respectively) with the characteristic two-segment architecture of the Tectiviridae. Both genomes encode homologs of the canonical tectiviral proteins (major capsid protein, packaging ATPase and DNA polymerase), as well as PRD1-type virion-associated transglycosylase and membrane DNA delivery proteins. Comparative genomics and phylogenetic analyses firmly establish that these two phages, together with Rhodococcusphage Toil, form a new genus within the Tectiviridae, which we have tentatively named Deltatectivirus. The identification of a cohesive clade of Actinobacteria-infecting tectiviruses with conserved genome structure but with scant sequence similarity to members of other tectiviral genera confirms that the Tectiviridae are an ancient lineage infecting a broad range of bacterial hosts.

Sex work in geographic perspective: a multi-disciplinary approach to mapping and understanding female sex work venues in Southwest China.

This paper examines the findings from an extensive geographic mapping study of female sex work venues located in the south western Chinese city of Zigong, in Sichuan province. Drawing upon the findings from quantitative research, secondary historical sources and field notes, composed during participant observation, we provide a nuanced portrait of how the operation of sex work can be conceptualised in spatial terms, where 'space' is regarded as something socially constructed and historically contingent. The sex work geographies we analyse hold important implications for prevention work conducted in the region. When the sexual practices between sex workers and their clients are viewed against a wider geographic and historical backdrop, focus shifts from the properties and intentionalities of individuals towards the kinds of spaces where sex work operates, the organisation of which are underpinned by economic forces that have given rise to the rapid proliferation of small urban spaces in contemporary China.