Therapeutic options for metastatic castration resistant prostate cancer : has the situation improved?

Limited treatment options for Castration Resistant Prostate Cancer (CRPC) still remain a major challenge. Despite therapeutic advances, most patients with malignant PCa have a poor prognosis. Since the year 2000, we have rapidly expanded our understanding of the molecular mechanisms underlying CRPC and this has led to an unprecedented number of new drug approvals within a short span of time. Recently, four new agents namely Abiraterone Acetate, Enzalutamide, Cabazitaxel, and Radium-223 have been shown to be effective in the post-chemotherapy setting in CRPC. The continued dependency of CRPC on androgen synthesis has seen the development of a number of new anti-androgen therapies, with abiraterone acetate and Enzalutamide being the most promising discoveries. Immunotherapeutic approaches have also found their niche in PCa with Sipuleucel-T shown to be effective in minimally asymptomatic CRPC. Research focussed on bone-targeting therapies has witnessed the arrival of promising new drugs with Denosumab and Radium-223 displaying improved survival of patients with CRPC. This review briefly discusses the findings and limitations from ongoing and completed clinical trials of novel treatments and regimens. In addition, potential mechanisms of therapy resistance and future challenges are discussed.

Using DNA as a drug - bioprocessing and delivery strategies

DNA may take a leading role in a future generation of blockbuster therapeutics. DNA has inherent advantages over other biomolecules such as protein, RNA and virus-like particles including safety, production simplicity and higher stability at ambient temperatures. Vaccination is the principal measure for preventing influenza and reducing the impact of pandemics; however, vaccines take up to 8-9 months to produce, and the global production capacity is woefully low. With production times as short as 2 weeks, improved safety and stability, bioprocess engineering developments, and the ability to perform numerous therapeutic roles, DNA has the potential to meet the demands of emerging and existing diseases. DNA is experiencing sharp growths in demand as indicated by its use in gene therapy trials and DNA vaccine related patents. Of particular interest for therapeutic use is plasmid DNA (pDNA), a form of non-genomic DNA that makes use of cellular machinery to express proteins or antigens. The production stages of fermentation and downstream purification are considered in this article. Forward looking approaches to purifying and delivering DNA are reported, including affinity chromatography and nasal inhalation. The place that pDNA may take in the preparation for and protection against pandemics is considered. If DNA therapeutics and vaccines prove to be effective, the ultimate scale of production will be huge which shall require associated bioprocess engineering research and development for purification of this large, unique biomolecule.

DNA molecules and human therapeutics

Nucleic acid molecules are championing a new generation of reverse engineered biopharmaceuticals. In terms of potential application in gene medicine, plasmid DNA (pDNA) vectors have exceptional therapeutic and immunological profiles as they are free from safety concerns associated with viral vectors, display non-toxicity and are simpler to develop. This review addresses the potential applications of pDNA molecules in vaccine design/development and gene therapy via recombinant DNA technology as well as a staged delivery mechanism for the introduction of plasmid-borne gene to target cells via the nasal route.

Non-market use and non-use values for preserving ecosystem services over time : a choice experiment application to coral reef ecosystems in New Caledonia

Non-use values (i.e. economic values assigned by individuals to ecosystem goods and services unrelated to current or future uses) provide one of the most compelling incentives for the preservation of ecosystems and biodiversity. Assessing the non-use values of non-users is relatively straightforward using stated preference methods, but the standard approaches for estimating non-use values of users (stated decomposition) have substantial shortcomings which undermine the robustness of their results. In this paper, we propose a pragmatic interpretation of non-use values to derive estimates that capture their main dimensions, based on the identification of a willingness to pay for ecosystem protection beyond one's expected life. We empirically test our approach using a choice experiment conducted on coral reef ecosystem protection in two coastal areas in New Caledonia with different institutional, cultural, environmental and socio-economic contexts. We compute individual willingness to pay estimates, and derive individual non-use value estimates using our interpretation. We find that, a minima, estimates of non-use values may comprise between 25 and 40% of the mean willingness to pay for ecosystem preservation, less than has been found in most studies.

Reduction of diesel engine exhaust emissions using non-thermal plasma technology

Non-thermal plasma (NTP) is a promising candidate for controlling engine exhaust emissions. Plasma is known as the fourth state of matter, where both electrons and positive ions co-exist. Both gaseous and particle emissions of diesel exhaust undergo chemical changes when they are exposed to plasma. In this project diesel particulate matter (DPM) mitigation from the actual diesel exhaust by using NTP technology has been studied. The effect of plasma, not only on PM mass but also on PM size distribution, physico-chemical structure of PM and PM removal mechanisms, has been investigated. It was found that NTP technology can significantly reduce both PM mass and number. However, under some circumstances particles can be formed by nucleation. Energy required to create the plasma with the current technology is higher than the benchmark set by the commonly used by the automotive industry. Further research will enable the mechanism of particle creation and energy consumption to be optimised.

Therapeutic practice with refugee clients: a qualitative study of therapist experience

Background There is limited research on the subjective experience of therapists and their understanding of therapeutic process when working with people from refugee backgrounds. Objective The present study provides a qualitative account of therapists’ conceptions of therapeutic practice and experiences of working therapeutically with refugee clients. Method Participants were 12 mental health workers who had worked therapeutically with people from refugee backgrounds, with an average of 7.6 years (range 1.5-16 years) experience in this field. Participants completed a semi-structured interview and completed a brief quantitative survey. Findings Thematic analysis revealed a number of super-ordinate themes. Four key themes are explored in the current study: principles of therapeutic practice; therapy as a relational experience; the role of context in informing therapeutic work with refugee clients; and the impact of therapeutic work on the therapist. Discussion The results revealed the complexity and demands of working with people from refugee backgrounds. Further, the lack of research evidence for the methods of therapeutic practice described in the current study highlights the distinction between naturalistic therapeutic practice and the current state of the evidence regarding therapeutic interventions for refugee clients. The findings have important implications for training and supporting therapists to work with people who have fled their countries of origin and who have often been exposed to highly traumatic events.