Conventional approaches for therapeutic targeting of viral pathogens have consistently faced obstacles arising from the development of resistant strains and a lack of broad-spectrum application. Influenza represents a particularly problematic therapeutic challenge since high viral mutation rates have often confounded many conventional antivirals. Newly emerging or engineered strains of influenza represent an even greater threat as typified by recent interest in avian subtypes of influenza. Based on the limitations associated with targeting virally-encoded molecules, we have taken an orthogonal approach of targeting host pathways in a manner that prevents viral propagation or spares the host from virus-mediated pathogenicity. To this end, we report herein the application of an improved technology for target discovery, Random Homozygous Gene Perturbation (RHGP), to identify host-oriented targets that are well-tolerated in normal cells but that prevent influenza-mediated killing of host cells. Improvements in RHGP facilitated a thorough screening of the entire genome, both for overexpression or loss of expression, to identify targets that render host cells resistant to influenza infection. We identify a set of host-oriented targets that prevent influenza killing of host cells and validate these targets using multiple approaches. These studies provide further support for a new paradigm to combat viral disease and demonstrate the power of RHGP to identify novel targets and mechanisms.
Background: Human Immunodeficiency Virus (HIV) is a global threat to public health. Current therapies that directly target the virus often are rendered ineffective due to the emergence of drugresistant viral variants. An emerging concept to combat drug resistance is the idea of targeting host mechanisms that are essential for the propagation of the virus, but have a minimal cellular effect.
Introduction Patient‐centred care (PCC) has come to the forefront for many institutions, funding agencies and clinicians, and is integrated into care. Does a disconnect in understanding still exist between patients, healthcare organizations and clinicians in what PCC means and how outstanding issues might be addressed? Methods We conducted interviews and focus groups with self‐reported chronic care patients and clinicians providing care to these patients exploring PCC experiences, expectations and practices. These data were initially analysed using inductive thematic analysis. This paper reports on the findings of a secondary analysis examining the alignment between patients and clinicians on five key predetermined dimensions of PCC. Results Eighteen patients participated, representing a range of chronic conditions. Thirty‐eight clinicians participated. One thousand and three hundred patient and 1800 clinician codes were identified and grouped into 5 main topics with 140 unique themes (patients) and 9 main topics with 54 unique themes (clinicians). A total of 166 quotes (patient = 93, clinician = 73) were identified for this PCC definition alignment analysis. Partial or complete alignment of patient and clinician perspectives was seen on most dimensions. Key disconnects were observed in patient involvement, patient empowerment and clinician–patient communication. Only 18% of patients reported experiencing patient‐centred communication, whereas 57% of clinicians reported using patient‐focused communication approaches. Conclusion Overall, study patients and clinicians endorse that many PCC elements occur. This study highlights key differences between patients and clinicians, suggesting persistent challenges. Clinician participants relayed their PCC approaches of informing and educating patients; however, patients often perceive these approaches as didactic, role‐diminishing and noncollaborative. Collaborative approaches, such as shared decision‐making, hold promise to bridge persistent PCC gaps and should be integrated into medical education programmes. Patient or Public Contribution This project was conceived and executed with a co‐design approach wherein patients with chronic conditions who are trained in research (i.e., see descriptions of Patient and Community Engagement Research in the text) were involved in all stages of the research project alongside other researchers on the project team. Healthcare providers were involved as participants and as principal investigators in the project.
Governments face challenges in resolving complex health and social policy conflicts, such as the community water fluoridation (CWF) impasse in Calgary. Track Two diplomacy, informal dialogues facilitated by an impartial third party, is proposed to address these issues amid epistemic conflict and declining public trust in fellow citizens, science, and government. This study examined Track Two diplomacy’s application in Calgary’s CWF policy conflict. Collaborating with policymakers and community partners, the research team explored a Track Two–CWF process and conducted 21 semi-structured interviews with policymakers, scholars, practitioners, observers, and civil society representatives. Data interpretation explored contextual factors, conflict transformation potential, and design features for a Track Two process. A conflict map revealed factors contributing to impasse: the polarizing nature of a binary policy question on fluoridation; disciplinary silos; failed public engagement; societal populism; societal lack of disposition to dialogue; individual factors (adverse impact of conflict on stakeholders, adherence to extreme positions, issue fatigue, apathy, and lack of humility); together with policy-making factors (perceived lack of leadership, lack of forum to dialogue, polarization and silos). Participants suggested reframing the issue as nonbinary, involving a skilled facilitator, convening academics, and considering multiple dialogue tracks for a Track Two process. The first theory of change would focus on personal attitudes, relationships, and culture. Participants expressed cautious optimism about Track Two diplomacy’s potential. Track Two diplomacy offers a promising approach to reframe intractable public health policy conflicts by moving stakeholders from adversarial positions to jointly assessing and solving problems. Further empirical evidence is needed to test the suggested process.
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