The ascidian natural product eusynstyelamide B is a novel topoisomerase II poison that induces DNA damage and growth arrest in prostate and breast cancer cells

As part of an anti-cancer natural product drug discovery program, we recently identified eusynstyelamide B (EB), which displayed cytotoxicity against MDA-MB-231 breast cancer cells (IC50 = 5 μM) and induced apoptosis. Here, we investigated the mechanism of action of EB in cancer cell lines of the prostate (LNCaP) and breast (MDA-MB-231). EB inhibited cell growth (IC50 = 5 μM) and induced a G2 cell cycle arrest, as shown by a significant increase in the G2/M cell population in the absence of elevated levels of the mitotic marker phospho-histone H3. In contrast to MDA-MB-231 cells, EB did not induce cell death in LNCaP cells when treated for up to 10 days. Transcript profiling and Ingenuity Pathway Analysis suggested that EB activated DNA damage pathways in LNCaP cells. Consistent with this, CHK2 phosphorylation was increased, p21CIP1/WAF1 was up-regulated and CDC2 expression strongly reduced by EB. Importantly, EB caused DNA double-strand breaks, yet did not directly interact with DNA. Analysis of topoisomerase II-mediated decatenation discovered that EB is a novel topoisomerase II poison.

Cosmoscapes and the promotion of uncosmopolitan values

Globality generates increasingly diffuse networks of human and non-human innovators, carriers and icons of exotic, polyethnic cosmopolitan difference; and this diffusion is increasingly hard to ignore or police (Latour 1993). In fact, such global networks of material-symbolic exchange can frequently have the unintended consequence of promoting status systems and cultural relationships founded on uncosmopolitan values such as cultural appropriation and status-based social exclusion. Moreover, this materialsymbolic engagement with cosmopolitan difference could also be rather mundane, engaged in routinely without any great reflexive consciousness or capacity to destabilise current relations of cultural power, or interpreted unproblematically as just one component of a person’s social environment. Indeed, Beck’s (2006) argument is that cosmopolitanism, in an age of global risk, is being forced upon us unwillingly, so there should be no surprise if it is a bitter pill for some to swallow. Within these emergent cosmopolitan networks, which we call ‘cosmoscapes’, there is no certainty about the development of ethical or behavioural stances consistent with claims foundational to the current literature on cosmopolitanism. Reviewing historical and contemporary studies of globality and its dynamic generative capacity, this paper considers such literatures in the context of studies of cultural consumption and social status. When one positions these diverse bodies of literature against one another, it becomes clear that the possibility of widespread cosmopolitan cultural formations is largely unpromising.

Zinc supplementation at conventional doses does not improve the disturbance of taste perception in hemodialysis patients

Objective: To determine the effect of zinc supplementation on taste perception in a group of hemodialysis patients. Design and Setting: Double-blind randomized placebo-controlled study in a teaching hospital dialysis unit. Patients: Fifteen stable hemodialysis patients randomized to placebo (6 male, 2 female; median age, 67; range, 30 to 72 years) or treatment (5 male, 2 female; median age, 60; range, 31 to 76 years). Intervention: Treatment group received zinc sulfate 220 mg per day for 6 weeks, and the placebo group received an apparently identical dummy pill. Main Outcome Measures: Taste scores by visual analogue scales, normalized protein catabolic rate and plasma, whole blood and red cell zinc levels. Results: At baseline, sweet and salt tastes were identified correctly by both groups. Sour was often confused with salt. Sour solutions of different concentrations were not distinguishable. Taste scores were not different after 6 weeks for either group. There was no significant increment in zinc levels or normalized protein catabolic rate for either group. Conclusion: We found a disturbance of taste perception in hemodialysis patients, particularly for the sour modality, which was not corrected by this regimen of zinc supplementation. These results cast doubts on the conclusions of earlier studies that indicated an improvement in taste after zinc supplementation.

Changing patterns of contraceptive use in Australian women

Background: This longitudinal analysis examines how patterns of contraceptive use changed over 11 years among Australian women born between 1973 and 1978. Study Design: The analysis included 6708 women sampled from the Australian universal health insurance database who completed four self-report postal surveys between 1996 and 2006. Change over time in use of any method of contraception and the common single methods of the oral contraceptive pill and condom was examined using a longitudinal logistic regression model. Results: The oral contraceptive pill was the most commonly used single method at each survey (27-44%) but decreased over time. Over time, contraceptive users were increasingly more likely to be single or in a de facto relationship or to have had two or more births. Conclusions: Women's contraceptive use and the factors associated with contraceptive use change over time as women move into relationships, try to conceive, have babies and complete their families.

Fertility and infertility : studies in reproductive epidemiology in Australia

Worldwide, there are few large-scale epidemiological studies on infertility. In Australia, population-based research on infertility is limited to a few small-scale studies. Therefore, the prevalence of infertility and unmet need for specialist medical advice and treatment cannot be estimated reliably. Women who have used assisted reproductive technologies (ART) are recorded in treatment registries. However, there are many infertile women who are excluded from these clinical populations because they neither seek advice nor use treatment. The thesis was based on a biopsychosocial model of health and used the methods of reproductive epidemiology to address the lack of national data on the prevalence of infertility in Australia. Firstly, numbers of births and pregnancy losses were investigated in two generations of women participating in the Australian Longitudinal Study on Women’s Health (ALSWH). The ALSWH is a broad-ranging, longitudinal examination of biological, psychological and social factors that impact on women’s health and wellbeing. Women from three age cohorts were randomly sampled from the population using the universal public health insurance (i.e., Medicare) database and ALSWH participants were representative of the female population. However, the studies in the thesis only involved data from two cohorts. The younger cohort were born in 1973-78 and completed up to four mailed surveys between 1996 (when they were aged 18-23 years, n=14247) and 2006 (28-33 years, n=9145). The mid-aged cohort were born in 1946-51 and completed four mailed surveys between 1996 (when they were aged 45-50 years n=13715) and 2004 (53-58 years, n=10905). Compared to other studies that focus on outcomes of single pregnancies, these studies included all pregnancy outcomes by developing comprehensive reproductive histories for each woman. Pregnancy outcomes included birth, miscarriage, stillbirth, termination and ectopic pregnancy. Women in the youngest cohort (born in 1973-78) were only just reaching their peak childbearing years and many (44%) had yet to report their first pregnancy outcome. Women from the mid-aged cohort (born 1946-51) had completed their reproductive lives and 92% were able to report on their lifetime pregnancy outcomes. Pregnancy losses, especially miscarriage, were common for both generations of women. Secondly, the prevalence of infertility, seeking medical advice and using treatment was identified for these two generations of women. For the older generation, the lifetime prevalence of infertility and demand for treatment was investigated in the context of the specialist medical services which became available circa 1980. By this time, however, most of these older women had already been pregnant and completed their families. For women who experienced infertility (11%), their options for advice and treatment were limited and less than half (42%) had used any treatment. More recently for the younger generation of women, who were aged 28-33 years in 2006, specialist advice and treatment were extensively available. Among women who had tried to conceive or had been pregnant (n=5936), 17% had experienced infertility and the majority (72%) were able to access medical advice. However, after seeking advice only half of these infertile women had used treatment with fertility hormones or in vitro fertilisation (IVF). Overall for infertile women aged up to 33 years, only one-third had used these treatments. Thirdly, the barriers to accessing medical advice and using treatment for infertility were identified for women aged less than 34 years. Among a community sample of infertile women aged 28-33 years (ALSWH participants), self-reported depression was found to be a barrier to accessing medical advice. The characteristics of these infertile women in the community who had (n=121) or had not (n=110) used treatment were compared to infertile women aged 27-33 years (n=59) attending four fertility clinics. Compared to infertile women in the community, living in major cities and having private health insurance were associated with early use of treatment for infertility at specialist clinics by women aged <34 years. In contrast to most clinical studies of IVF, the final study reported in the thesis took into account repeated IVF cycles and the impact of women’s individual histories on IVF outcomes. Among 121 infertile women (aged 27-46 years) who had 286 IVF cycles, older age and prolonged use of the oral contraceptive pill were associated with fewer eggs collected. Further, women in particular occupations had lower proportions of eggs fertilised normally than women in other occupational groups. These studies form the first large-scale epidemiological examination of infertility in Australia. The finding that two-thirds of women with infertility had not used treatment indicates that there is an unmet need for specialist treatment in women aged less than 34 years. However, barriers to accessing treatment prevent women using ART at a younger age when there is a higher chance of pregnancy.

Reproductive health : findings from the Australian Longitudinal Study on Women’s Health. Chapter 3: Use of contraception

Chapter 3: Use of contraception. p15-32 Key findings: This section examines trends in the use of contraception between 1996 and 2006 by women who participated in the surveys for the 1973-1978 cohort of the Australian Longitudinal Study on Women’s Health. 1. The oral contraceptive pill was the most commonly used method of contraception at each survey, but its use decreased over time. 2.Of women who consistently used contraception, 40% used the oral contraceptive pill as their only method of contraception in at least three out of four surveys. 3. The proportion of women using condoms as their only method of contraception remained steady over time (15-18%) but only 3% of all women used condoms only at every survey. 4. The proportion of women using both condoms and the oral contraceptive pill remained steady at 13-14% of all women from Survey 1 to 3, but decreased to 8% of all women at Survey 4. 5. The use of methods other than the oral contraceptive pill and/or condoms increased at Survey 4. 6. The proportion of women using an implant (e.g. Implanon) remained steady between Surveys 3 and 4, with 3% of women using an implant only. Around one third of implant users at Survey 3 continued to use this method at Survey 4. 7. The main reasons for not using contraception at Surveys 3 and 4 were pregnancy, trying to conceive, or no male sexual partners. 8. Women who used contraception were more likely to be in de facto relationships or single, be up to date with Pap tests and have had two or more births. 9. Women who did not use contraception were more likely to be non-drinkers and/or do low levels of exercise, have had one birth and have experienced miscarriage. 10. Contraception changed in expected ways according to reproductive events: women who reported only miscarriages between surveys also stopped using contraception in the same period; most women who did not report reproductive events continued to use the same method of contraception; and women who had a termination tended to switch methods.

“As many options as there are, there are just not enough for me” : a qualitative analysis of contraceptive use and barriers to access among Australian women

There is currently little information available about reasons for contraceptive use or non-use among young Australian women and the reasons for choosing specific types of contraceptive methods. A comprehensive life course perspective of women's experiences in using and obtaining contraceptives is lacking, particularly relating to women's perceived or physical barriers to access. This paper presents an analysis of qualitative data gathered from free-text comments provided by women born between 1973 and 1978 as part of their participation in the Australian Longitudinal Study on Women's Health. The Australian Longitudinal Study on Women's Health is a large cohort study involving over 40,000 women from three age groups (aged 18-23, aged 40-45 and aged 70-75) who were selected from the database of Medicare the Australian universal health insurance system in 1995. The women have been surveyed every 3 years about their health by mailed self-report surveys, and more recently online. Written comments from 690 women across five surveys from 1996 (when they were aged 18-23 years) to 2009 (aged 31-36 years) were examined. Factors relating to contraceptive use and barriers to access were identified and explored using thematic analysis. Side-effects, method satisfaction, family timing, and hormonal balance were relevant to young women using contraception. Most women who commented about a specific contraceptive method wrote about the oral contraceptive pill. While many women were positive or neutral about their method, noting its convenience or non-contraceptive benefits, many others were concerned about adverse effects, affordability, method failure, and lack of choice. Negative experiences with health services, lack of information, and cost were identified as barriers to access. As the cohort aged over time, method choice, changing patterns of use, side-effects, and negative experiences with health services remained important themes. Side-effects, convenience, and family timing play important roles in young Australian women's experiences of contraception and barriers to access. Contrary to assumptions, barriers to contraceptive access continue to be experienced by young women as they move into adulthood. Further research is needed about how to decrease barriers to contraceptive use and minimise negative experiences in order to ensure optimal contraceptive access for Australian women.

Contraceptive use and unintended pregnancy among 18-23 year old women in Australia : the first findings of the CUPID study

Objectives: Little is known about young adult women's experience of unintended pregnancy in Australia, nor the extent to which ineffective contraceptive use or contraceptive failure may lead to young women becoming pregnant. The CUPID study is the first in Australia to examine young adult Australian women's patterns of contraceptive use, their experience of unintended pregnancy, and their use (or not) of contraception at the time of conception. Methods: Australian women aged 18-23 years completed an online survey about contraceptive use and experience of unintended pregnancy. They were recruited through a range of methods including advertising on Facebook, and snowball sampling. Sample representativeness was established through comparison with Census data. Results: Of the 511 respondents, 403 women reported that they had ever had sex and were not currently pregnant. Among these women, the pill was the most common method of contraception used on the most recent occasion, used alone (30%) or with condoms (21%). Condoms (alone or with another method other than the pill) were used by a further 17%, and long-acting contraceptive methods by a further 16%. Other methods such as natural methods or partner vasectomy were used by 16%. The withdrawal method was surprisingly common and was mentioned by 15% of the women overall, usually in combination with another method. There were 63 women who had been pregnant, including 5 who were pregnant at the time of the survey, and of these 55 (87%) had become pregnant by accident. Of these 55 women, 69% reported using a range of contraception methods when they became pregnant by accident: Pill only (29%) and in combination with condoms (3%) and withdrawal (5%); condoms only (18%) and in combination with withdrawal (16%); emergency contraceptive pill only (3%) and in combination with withdrawal (3%) and withdrawal only (24%). Conclusions: This study highlighted the use of less effective methods of contraception among young Australian women. The withdrawal method was commonly used, often in combination with other methods, particularly before an unintended pregnancy. Among the women who had been pregnant, most reported that their pregnancy had been unintended. A third of the young women who had experienced an unintended pregnancy were using the withdrawal method. Further research is needed about the place of the withdrawal method in the contraceptive practices of young women.

“As many options as there are, there are just not enough for me” : a qualitative analysis of contraceptive use and barriers to access among Australian women

There is currently little information available about reasons for contraceptive use or non-use among young Australian women and the reasons for choosing specific types of contraceptive methods. A comprehensive life course perspective of women's experiences in using and obtaining contraceptives is lacking, particularly relating to women's perceived or physical barriers to access. This paper presents an analysis of qualitative data gathered from free-text comments provided by women born between 1973 and 1978 as part of their participation in the Australian Longitudinal Study on Women's Health. The Australian Longitudinal Study on Women's Health is a large cohort study involving over 40,000 women from three age groups (aged 18-23, aged 40-45 and aged 70-75) who were selected from the database of Medicare the Australian universal health insurance system in 1995. The women have been surveyed every 3 years about their health by mailed self-report surveys, and more recently online. Written comments from 690 women across five surveys from 1996 (when they were aged 18-23 years) to 2009 (aged 31-36 years) were examined. Factors relating to contraceptive use and barriers to access were identified and explored using thematic analysis. Side-effects, method satisfaction, family timing, and hormonal balance were relevant to young women using contraception. Most women who commented about a specific contraceptive method wrote about the oral contraceptive pill. While many women were positive or neutral about their method, noting its convenience or non-contraceptive benefits, many others were concerned about adverse effects, affordability, method failure, and lack of choice. Negative experiences with health services, lack of information, and cost were identified as barriers to access. As the cohort aged over time, method choice, changing patterns of use, side-effects, and negative experiences with health services remained important themes. Side-effects, convenience, and family timing play important roles in young Australian women's experiences of contraception and barriers to access. Contrary to assumptions, barriers to contraceptive access continue to be experienced by young women as they move into adulthood. Further research is needed about how to decrease barriers to contraceptive use and minimise negative experiences in order to ensure optimal contraceptive access for Australian women.

The Chemistry of Mycotoxins

Mycotoxins – from the Greek μύκης (mykes, mukos) “fungus” and the Latin (toxicum) “poison” – are a large and growing family of secondary metabolites and hence natural products produced by fungi, in particular by molds (1). It is estimated that well over 1,000 mycotoxins have been isolated and characterized so far, but this number will increase over the next few decades due the availability of more specialized analytical tools and the increasing number of fungi being isolated. However, the most important classes of fungi responsible for these compounds are Alternaria, Aspergillus (multiple forms), Penicillium, and Stachybotrys. The biological activity of mycotoxins ranges from weak and/or sometimes positive effects such as antibacterial activity (e.g. penicillin derivatives derived from Penicillium strains) to strong mutagenic (e.g. aflatoxins, patulin), carcinogenic (e.g. aflatoxins), teratogenic, neurotoxic (e.g. ochratoxins), nephrotoxic (e.g. fumonisins, citrinin), hepatotoxic, and immunotoxic (e.g. ochratoxins, diketopiperazines) activities (1, 2), which are discussed in detail in this volume.

Catalytic activity evaluation of industrial Pd/C catalyst via gray-box dynamic modeling and simulation of hydropurification reactor

In this paper, dynamic modeling and simulation of the hydropurification reactor in a purified terephthalic acid production plant has been investigated by gray-box technique to evaluate the catalytic activity of palladium supported on carbon (0.5 wt.% Pd/C) catalyst. The reaction kinetics and catalyst deactivation trend have been modeled by employing artificial neural network (ANN). The network output has been incorporated with the reactor first principle model (FPM). The simulation results reveal that the gray-box model (FPM and ANN) is about 32 percent more accurate than FPM. The model demonstrates that the catalyst is deactivated after eleven months. Moreover, the catalyst lifetime decreases about two and half months in case of 7 percent increase of reactor feed flowrate. It is predicted that 10 percent enhancement of hydrogen flowrate promotes catalyst lifetime at the amount of one month. Additionally, the enhancement of 4-carboxybenzaldehyde concentration in the reactor feed improves CO and benzoic acid synthesis. CO is a poison to the catalyst, and benzoic acid might affect the product quality. The model can be applied into actual working plants to analyze the Pd/C catalyst efficient functioning and the catalytic reactor performance.

Health care consumers’ perspectives on pharmacist integration into private general practitioner clinics in Malaysia: A qualitative study

Background Pharmacists are considered medication experts but are underutilized and exist mainly at the periphery of the Malaysian primary health care team. Private general practitioners (GPs) in Malaysia are granted rights under the Poison Act 1952 to prescribe and dispense medications at their primary care clinics. As most consumers obtain their medications from their GPs, community pharmacists’ involvement in ensuring safe use of medicines is limited. The integration of a pharmacist into private GP clinics has the potential to contribute to quality use of medicines. This study aims to explore health care consumers’ views on the integration of pharmacists within private GP clinics in Malaysia. Methods A purposive sample of health care consumers in Selangor and Kuala Lumpur, Malaysia, were invited to participate in focus groups and semi-structured interviews. Sessions were audio recorded and transcribed verbatim and thematically analyzed using NVivo 10. Results A total of 24 health care consumers participated in two focus groups and six semi-structured interviews. Four major themes were identified: 1) pharmacists’ role viewed mainly as supplying medications, 2) readiness to accept pharmacists in private GP clinics, 3) willingness to pay for pharmacy services, and 4) concerns about GPs’ resistance to pharmacist integration. Consumers felt that a pharmacist integrated into a private GP clinic could offer potential benefits such as to provide trustworthy information on the use and potential side effects of medications and screening for medication misadventure. The potential increase in costs passed on to consumers and GPs’ reluctance were perceived as barriers to integration. Conclusion This study provides insights into consumers’ perspectives on the roles of pharmacists within private GP clinics in Malaysia. Consumers generally supported pharmacist integration into private primary health care clinics. However, for pharmacists to expand their capacity in providing integrated and collaborative primary care services to consumers, barriers to pharmacist integration need to be addressed.

Alive SMC^2: Bayesian model selection for low-count time series models with intractable likelihoods

In this paper we present a new method for performing Bayesian parameter inference and model choice for low count time series models with intractable likelihoods. The method involves incorporating an alive particle filter within a sequential Monte Carlo (SMC) algorithm to create a novel pseudo-marginal algorithm, which we refer to as alive SMC^2. The advantages of this approach over competing approaches is that it is naturally adaptive, it does not involve between-model proposals required in reversible jump Markov chain Monte Carlo and does not rely on potentially rough approximations. The algorithm is demonstrated on Markov process and integer autoregressive moving average models applied to real biological datasets of hospital-acquired pathogen incidence, animal health time series and the cumulative number of poison disease cases in mule deer.

Turing and the Trans-Pacific Partnership: Intellectual Property, Public Health, and Access to Essential Medicines

A recent controversy in the United States over drug pricing by Turing Pharmaceuticals AG has raised larger issues in respect of intellectual property, access to medicines, and the Trans-Pacific Partnership (TPP). In August 2015, Turing Pharmaceuticals AG – a private biopharmaceutical company with offices in New York, the United States, and Zug, Switzerland - acquired the exclusive marketing rights to Daraprim in the United States from Impax Laboratories Incorporated. Martin Shkreli, Turing’s Founder and Chief Executive Officer, maintained: “The acquisition of Daraprim and our toxoplasmosis research program are significant steps along Turing’s path of bringing novel medications to patients with serious disorders, some of whom often go undiagnosed and untreated.” He emphasised: “We intend to invest in the development of new drug candidates that we hope will yield an even better clinical profile, and also plan to launch an educational effort to help raise awareness and improve diagnosis for patients with toxoplasmosis.” In September 2015, there was much public controversy over the decision of Martin Shkreli to raise the price of a 62 year old drug, Daraprim, from $US13.50 to $US750 a pill. The drug is particularly useful in respect to the treatment and prevention of malaria, and in the treatment of infections in individuals with HIV/AIDS. Daraprim is listed on the World Health Organization’s (WHO) List of Essential Medicines. In the face of much criticism, Martin Shkreli has said that he will reduce the price of Daraprim. He observed: “We've agreed to lower the price on Daraprim to a point that is more affordable and is able to allow the company to make a profit, but a very small profit.” He maintained: “We think these changes will be welcomed.” However, he has been vague and ambiguous about the nature of the commitment. Notably, the lobby group, Pharmaceutical Research and Manufacturers of America (PhARMA), disassociated itself from the claims of Turing Pharmaceuticals. The group said: “PhRMA members have a long history of drug discovery and innovation that has led to increased longevity and improved lives for millions of patients.” The group noted: “Turing Pharmaceutical is not a member of PhRMA and we do not embrace either their recent actions or the conduct of their CEO.” The biotechnology peak body Biotechnology Industry Organization also sought to distance itself from Turing Pharmaceuticals. A hot topic: United States political debate about access to affordable medicines This controversy over Daraprim is unusual – given the age of drug concerned. Daraprim is not subject to patent protection. Nonetheless, there remains a monopoly in respect of the marketplace. Drug pricing is not an isolated problem. There have been many concerns about drug pricing – particularly in respect of essential medicines for HIV/AIDS, tuberculosis, and malaria. This recent controversy is part of a larger debate about access to affordable medicines. The dispute raises larger issues about healthcare, consumer rights, competition policy, and trade. The Daraprim controversy has provided impetus for law reform in the US. US Presidential Candidate Hillary Clinton commented: “Price gouging like this in this specialty drug market is outrageous.” In response to her comments, the Nasdaq Biotechnology Index fell sharply. Hillary Clinton has announced a prescription drug reform plan to protect consumers and promote innovation – while putting an end to profiteering. On her campaign site, she has emphasised that “affordable healthcare is a basic human right.” Her rival progressive candidate, Bernie Sanders, was also concerned about the price hike. He wrote a letter to Martin Shkreli, complaining about the price increase for the drug Daraprim. Sanders said: “The enormous, overnight price increase for Daraprim is just the latest in a long list of skyrocketing price increases for certain critical medications.” He has pushed for reforms to intellectual property to make medicines affordable. The TPP and intellectual property The Daraprim controversy and political debate raises further issues about the design of the TPP. The dispute highlights the dangers of extending the rights of pharmaceutical drug companies under intellectual property, investor-state dispute settlement, and drug administration. Recently, the civil society group Knowledge Ecology International published a leaked draft of the Intellectual Property Chapter of the TPP. Knowledge Ecology International Director, James Love, was concerned the text revealed that the US “continues to be the most aggressive supporter of expanded intellectual property rights for drug companies.” He was concerned that “the proposals contained in the TPP will harm consumers and in some cases block innovation.” James Love feared: “In countless ways, the Obama Administration has sought to expand and extend drug monopolies and raise drug prices.” He maintained: “The astonishing collection of proposals pandering to big drug companies make more difficult the task of ensuring access to drugs for the treatment of cancer and other diseases and conditions.” Love called for a different approach to intellectual property and trade: “Rather than focusing on more intellectual property rights for drug companies, and a death-inducing spiral of higher prices and access barriers, the trade agreement could seek new norms to expand the funding of medical research and development (R&D) as a public good, an area where the US has an admirable track record, such as the public funding of research at the National Institutes of Health (NIH) and other federal agencies.” In addition, there has been much concern about the Investment Chapter of the TPP. The investor-state dispute settlement regime would enable foreign investors to challenge government policy making, which affected their investments. In the context of healthcare, there is a worry that pharmaceutical drug companies will deploy their investor rights to challenge public health measures – such as, for instance, initiatives to curb drug pricing and profiteering. Such concerns are not merely theoretical. Eli Lilly has brought an investor action against the Canadian Government over the rejection of its drug patents under the investor-state dispute settlement regime of the North American Free Trade Agreement (NAFTA). The Health Annex to the TPP also raises worries that pharmaceutical drug companies will able to object to regulatory procedures in respect of healthcare. It is disappointing that the TPP – in the leaks that we have seen – has only limited recognition of the importance of access to essential medicines. There is a need to ensure that there are proper safeguards to provide access to essential medicines – particularly in respect of HIV/AIDs, malaria, and tuberculosis. Moreover, there must be protection against drug profiteering and price gouging in any trade agreement. There should be strong measures against the abuse of intellectual property rights. The dispute over Turing Pharmaceuticals AG and Daraprim is an important cautionary warning in respect of some of the dangers present in the secret negotiations in respect of the TPP. There is a need to preserve consumer rights, competition policy, and public health in trade negotiations over an agreement covering the Pacific Rim.