Key ethical issues discussed at CDC-sponsored international, regional meetings to explore cultural perspectives and contexts on pandemic influenza preparedness and response

Background: Recognizing the importance of having a broad exploration of how cultural perspectives may shape thinking about ethical considerations, the Centers for Disease Control and Prevention (CDC) funded four regional meetings in Africa, Asia, Latin America, and the Eastern Mediterranean to explore these perspectives relevant to pandemic influenza preparedness and response. The meetings were attended by 168 health professionals, scientists, academics, ethicists, religious leaders, and other community members representing 40 countries in these regions. Methods: We reviewed the meeting reports, notes and stories and mapped outcomes to the key ethical challenges for pandemic influenza response described in the World Health Organization’s (WHO’s) guidance, Ethical Considerations in Developing a Public Health Response to Pandemic Influenza: transparency and public engagement, allocation of resources, social distancing, obligations to and of healthcare workers, and international collaboration. Results: The important role of transparency and public engagement were widely accepted among participants. However, there was general agreement that no “one size fits all” approach to allocating resources can address the variety of economic, cultural and other contextual factors that must be taken into account. The importance of social distancing as a tool to limit disease transmission was also recognized, but the difficulties associated with this measure were acknowledged. There was agreement that healthcare workers often have competing obligations and that government has a responsibility to assist healthcare workers in doing their job by providing appropriate training and equipment. Finally, there was agreement about the importance of international collaboration for combating global health threats. Conclusion: Although some cultural differences in the values that frame pandemic preparedness and response efforts were observed, participants generally agreed on the key ethical principles discussed in the WHO’s guidance. Most significantly the input gathered from these regional meetings pointed to the important role that procedural ethics can play in bringing people and countries together to respond to the shared health threat posed by a pandemic influenza despite the existence of cultural differences

Social Connection, Relationships and Older Lesbian and Gay People

This paper presents data from a small study exploring the impacts of homophobia on the lives of older lesbian and gay Australians. Eleven in-depth interviews were conducted with older lesbians (6) and gay men (5) ranging in age from 65 to 79 years. The study found that participants’ sense of self was shaped by the dominant medical, legal and religious institutions of their youth that defined them as sick, immoral or criminal. Participants described enforced “cure” therapies, being imprisoned, having employment terminated and being disowned and disinherited by family. In this context, intimate relationships and social networks provided refuge where trust was rebuilt and sexuality affirmed. Many created safe spaces for themselves. This equilibrium was threatened with increasing age, disability and the reliance on health and social services. Participants feared a return to institutional control and a need to “straighten up” or hide their sexuality. In response, partners stepped into the role of caregiver, at times beyond their capacity and at a cost to their relationship. The study describes the importance of understanding social connections in the lives of older lesbians and gay men. It highlights the need for inclusive services to ensure that social networks are supported and that health and well-being are promoted

Effect of Patient Age on Management Decisions in Breast Cancer: Consensus from a National Consultation

This qualitative study investigated attitudes, perceptions, and practices of breast cancer specialists with reference to the effect of patient age on management decisions in breast cancer, and attempted to identify national consensus on this issue

Cytoplasmic expression systems triggered by mRNA yield increased gene expression in post-mitotic neurons

Non-viral vectors are promising vehicles for gene therapy but delivery of plasmid DNA to post-mitotic cells is challenging as nuclear entry is particularly inefficient. We have developed and evaluated a hybrid mRNA/DNA system designed to bypass the nuclear barrier to transfection and facilitate cytoplasmic gene expression. This system, based on co-delivery of mRNA(A64) encoding for T7 RNA polymerase (T7 RNAP) with a T7-driven plasmid, produced between 10- and 2200-fold higher gene expression in primary dorsal root ganglion neuronal (DRGN) cultures isolated from Sprague–Dawley rats compared to a cytomegalovirus (CMV)-driven plasmid, and 30-fold greater expression than the enhanced T7-based autogene plasmid pR011. Cell-free assays and in vitro transfections highlighted the versatility of this system with small quantities of T7 RNAP mRNA required to mediate expression at levels that were significantly greater than with the T7-driven plasmid alone or supplemented with T7 RNAP protein. We have also characterized a number of parameters, such as mRNA structure, intracellular stability and persistence of each nucleic acid component that represent important factors in determining the transfection efficiency of this hybrid expression system. The results from this study demonstrate that co-delivery of mRNA is a promising strategy to yield increased expression with plasmid DNA, and represents an important step towards improving the capability of non-viral vectors to mediate efficient gene transfer in cell types, such as in DRGN, where the nuclear membrane is a significant barrier to transfection

Key Ethical Issues Discussed at CDC-Sponsored International, Regional Meetings to Explore Cultural Perspectives and Contexts on Pandemic Influenza Preparedness and Response

Background: Recognizing the importance of having a broad exploration of how cultural perspectives may shape thinking about ethical considerations, the Centers for Disease Control and Prevention (CDC) funded four regional meetings in Africa, Asia, Latin America, and the Eastern Mediterranean to explore these perspectives relevant to pandemic influenza preparedness and response. The meetings were attended by 168 health professionals, scientists, academics, ethicists, religious leaders, and other community members representing 40 countries in these regions. Methods: We reviewed the meeting reports, notes and stories and mapped outcomes to the key ethical challenges for pandemic influenza response described in the World Health Organization’s (WHO’s) guidance, Ethical Considerations in Developing a Public Health Response to Pandemic Influenza: transparency and public engagement, allocation of resources, social distancing, obligations to and of healthcare workers, and international collaboration. Results: The important role of transparency and public engagement were widely accepted among participants. However, there was general agreement that no “one size fits all” approach to allocating resources can address the variety of economic, cultural and other contextual factors that must be taken into account. The importance of social distancing as a tool to limit disease transmission was also recognized, but the difficulties associated with this measure were acknowledged. There was agreement that healthcare workers often have competing obligations and that government has a responsibility to assist healthcare workers in doing their job by providing appropriate training and equipment. Finally, there was agreement about the importance of international collaboration for combating global health threats. Conclusion: Although some cultural differences in the values that frame pandemic preparedness and response efforts were observed, participants generally agreed on the key ethical principles discussed in the WHO’s guidance. Most significantly the input gathered from these regional meetings pointed to the important role that procedural ethics can play in bringing people and countries together to respond to the shared health threat posed by a pandemic influenza despite the existence of cultural differences

A versatile reducible polycation-based system for efficient delivery of a broad range of nucleic acids

Synthetic vectors based on reducible polycations consisting of histidine and polylysine residues (HIS RPCs) were evaluated for their ability to deliver nucleic acids. Initial experiments showed that RPC-based vectors with at least 70% histidine content mediated efficient levels of gene transfer without requirement for the endosomolytic agent chloroquine. Significant gene transfer was observed in a range of cell types achieving up to a 5-fold increase in the percentage of transfected cells compared to 25 kDa PEI, a gold standard synthetic vector. In contrast to 25 kDa PEI, HIS RPCs also mediated efficient transfer of other nucleic acids, including mRNA encoding green fluorescent protein in PC-3 cells and siRNA directed against the neurotrophin receptor p75(NTR) in post-mitotic cultures of rat dorsal root ganglion cell neurons. Experiments to elevate intracellular glutathione and linear profiling of cell images captured by multiphoton fluorescent microscopy highlighted that parameters such as the molecular weight and rate of cleavage of HIS RPCs were important factors in determining transfection activity. Altogether, these results demonstrate that HIS RPCs represent a novel and versatile type of vector that can be used for efficient cytoplasmic delivery of a broad range of nucleic acids. This should enable different or a combination of therapeutic strategies to be evaluated using a single type of polycation-based vector

Focused Ion Beam Fabrication

Contains reports on five research projects.DARPA/Naval Electronic Systems Command (Contract MDA-903-85-C-0215)Charles Stark Draper Laboratory (Contract DL-H-261827)U.S. Navy - Office of Naval Research (Contract N00014-84-K-0073)Nippon Telephone and TelegraphHitachi Central Research Laborator

1958: Abilene Christian College Bible Lectures - Full Text

“GOD” Being the Abilene Christian College Annual Bible Lectures 1958 Price: $3.00 Published by FIRM FOUNDATION PUBLISHING HOUSE Box 77 Austin, Texa

Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience

Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue