The Jean Chretien Pledge to Africa act: Patent law and humanitarian aid

This article evaluates the implementation of the WTO General Council Decision in 2003, which resolved that developed nations could export patented pharmaceutical drugs to member states in order to address public health issues - such as HIV/AIDS, tuberculosis, malaria and other epidemics. The Jean Chretien Pledge to Africa Act 2004 (Canada) provides authorisation for the export of pharmaceutical drugs from Canada to developing countries to address public health epidemics. The European Union has issued draft regulations governing the export of pharmaceutical drugs. A number of European countries - including Norway, the Netherlands, France, and Switzerland - are seeking to pass domestic legislation to give force to the WTO General Council Decision. Australia has shown little initiative in seeking to implement such international agreements dealing with access to essential medicines. It is argued that Australia should implement humanitarian legislation to embody the WTO General Council Decision, emulating models in Canada, Norway, and the European Union. Ideally, there should be no right of first refusal; the list of pharmaceutical drugs should be open-ended; and the eligible importing countries should not be limited to members of the WTO.

Integration over song classification replicates: song variant analysis in the hihi

Human expert analyses are commonly used in bioacoustic studies and can potentially limit the reproducibility of these results. In this paper, a machine learning method is presented to statistically classify avian vocalizations. Automated approaches were applied to isolate bird songs from long field recordings, assess song similarities, and classify songs into distinct variants. Because no positive controls were available to assess the true classification of variants, multiple replicates of automatic classification of song variants were analyzed to investigate clustering uncertainty. The automatic classifications were more similar to the expert classifications than expected by chance. Application of these methods demonstrated the presence of discrete song variants in an island population of the New Zealand hihi (Notiomystis cincta). The geographic patterns of song variation were then revealed by integrating over classification replicates. Because this automated approach considers variation in song variant classification, it reduces potential human bias and facilitates the reproducibility of the results.

Connecting soundscape to landscape: Which acoustic index best describes landscape configuration?

Soundscape assessment has been proposed as a remote ecological monitoring tool for measuring biodiversity, but few studies have examined how soundscape patterns vary with landscape configuration and condition. The goal of our study was to examine a suite of published acoustic indices to determine whether they provide comparable results relative to varying levels of landscape fragmentation and ecological condition in nineteen forest sites in eastern Australia. Our comparison of six acoustic indices according to time of day revealed that two indices, the acoustic complexity and the bioacoustic index, presented a similar pattern that was linked to avian song intensity, but was not related to landscape and biodiversity attributes. The diversity indices, acoustic entropy and acoustic diversity, and the normalized difference soundscape index revealed high nighttime sound, as well as a dawn and dusk chorus. These indices appear to be sensitive to nocturnal biodiversity which is abundant at night in warm, subtropical environments. We argue that there is need to better understand temporal partitioning of the soundscape by specific taxonomic groups, and this should involve integrated research on amphibians, insects and birds during a 24 h cycle. The three indices that best connected the soundscape with landscape characteristics, ecological condition and bird species richness were acoustic entropy, acoustic evenness and the normalized difference soundscape index. This study has demonstrated that remote soundscape assessment can be implemented as an ecological monitoring tool in fragmented Australian forest landscapes. However, further investigation should be dedicated to refining and/or combining existing acoustic indices and also to determine if these indices are appropriate in other landscapes and for other survey purposes.

Incentives for global public health: Patent law and access to essential medicines

This portrait of the global debate over patent law and access to essential medicines focuses on public health concerns about HIV/AIDS, malaria, tuberculosis, the SARS virus, influenza, and diseases of poverty. The essays explore the diplomatic negotiations and disputes in key international fora, such as the World Trade Organization, the World Health Organization and the World Intellectual Property Organization. Drawing upon international trade law, innovation policy, intellectual property law, health law, human rights and philosophy, the authors seek to canvass policy solutions which encourage and reward worthwhile pharmaceutical innovation while ensuring affordable access to advanced medicines. A number of creative policy options are critically assessed, including the development of a Health Impact Fund, prizes for medical innovation, the use of patent pools, open-source drug development and forms of 'creative capitalism'.

Clustering acoustic events in environmental recordings for species richness surveys

Environmental acoustic recordings can be used to perform avian species richness surveys, whereby a trained ornithologist can observe the species present by listening to the recording. This could be made more efficient by using computational methods for iteratively selecting the richest parts of a long recording for the human observer to listen to, a process known as “smart sampling”. This allows scaling up to much larger ecological datasets. In this paper we explore computational approaches based on information and diversity of selected samples. We propose to use an event detection algorithm to estimate the amount of information present in each sample. We further propose to cluster the detected events for a better estimate of this amount of information. Additionally, we present a time dispersal approach to estimating diversity between iteratively selected samples. Combinations of approaches were evaluated on seven 24-hour recordings that have been manually labeled by bird watchers. The results show that on average all the methods we have explored would allow annotators to observe more new species in fewer minutes compared to a baseline of random sampling at dawn.

Mauve: How one man invented the colour that changed the world

In an essay, "The Books of Last Things", Delia Falconer discusses the emergence of a new genre in publishing - microhistories. She cites a number of recent titles in non-fiction and fiction - Longitude, Cod, Tulips, Pushkin's Button, Nathaniel's Nutmeg, Zarafa, The Surgeon of Crowthorne, The Potato, The Perfect Storm. Delia Falconer observes of this tradition: "One has the sense, reading these books, of a surprising weight, of pleasant shock. In part, it is because we are looking at things which are generally present around us, but modestly out of sight and mind - historical nitty gritty like cod, potatoes, longitudinal clocks - which the authors have thrust suddenly, like a Biblical visitation of frogs or locusts, in our face. Things like spice and buttons and clocks are generally seen to enable history on the large scale, but are not often viewed as its worthy subjects. And by the same grand logic of history, more unusual phenomena like cabinets of curiosities or glass-making or farm lore or sailors' knots are simply odd blips on its radar screen, interesting footnotes. These new books, microhistories, reverse the usual order of history, which argues from the general to the particular, in order to prove its inevitable progress. They start from the footnotes. But by reversing the process, and walking through the back door of history, you don't necessarily end up at the front of the same house." Delia Falconer speculates about the reasons for the popularity of microhistories. She concludes: "I would like to think that reading them is not simply an exercise in nostalgia, but a challenge to the present". In Mauve, Simon Garfield provides a new way of thinking and writing about the history of intellectual property. Instead of providing a grand historical narrative of intellectual property, he tells the story of a particular invention, and its exploitation. Simon Garfield relates how English chemist William Perkin accidentally discovered a way to mass-produce colour mauve in a factory. Working on a treatment for malaria in his London home laboratory, Perkin failed to produce artificial quinine. Instead he created a dark oily sludge that turned silk a beautiful light purple. The colour was unique and became the most desirable shade in the fashion houses of Paris and London. ... The book Mauve will have a number of contemporary resonances for intellectual property lawyers and academics. Simon Garfield emphasizes the difficulties inherent in commercialising an invention and managing intellectual property. He investigates the uneasy collaboration between industry and science. Simon Garfield suggests that complaints about the efficacy of patent offices are perennial. He also highlights the problems faced by courts and law-makers in accommodating new technologies within the logic of patent law. In his elegant microhistory of the colour mauve, Simon Garfield confirms the conclusion of Brad Sherman and Lionel Bently that many aspects of modern intellectual property law can only be understood through an understanding of the past: "The image of intellectual property law that developed during the 19th century and the narrative of identity which this engendered played and continue to play an important role in the way we think about and understand intellectual property law".

The Doha deadlock: Intellectual property and climate change

In November 2001, Doha hosted trade talks over intellectual property and public health. The discussions resulted in the landmark Doha Declaration on the TRIPS Agreement and Public Health. The Doha Declaration recognised “that the TRIPS Agreement does not and should not prevent members from taking measures to protect public health” - particularly in relation to HIV/AIDS, tuberculosis, malaria and other epidemics.

Role of enhanced vector transmission of a new West Nile virus strain in an outbreak of equine disease in Australia in 2011

Background In 2011, a variant of West Nile virus Kunjin strain (WNVKUN) caused an unprecedented epidemic of neurological disease in horses in southeast Australia, resulting in almost 1,000 cases and a 9% fatality rate. We investigated whether increased fitness of the virus in the primary vector, Culex annulirostris, and another potential vector, Culex australicus, contributed to the widespread nature of the outbreak. Methods Mosquitoes were exposed to infectious blood meals containing either the virus strain responsible for the outbreak, designated WNVKUN2011, or WNVKUN2009, a strain of low virulence that is typical of historical strains of this virus. WNVKUN infection in mosquito samples was detected using a fixed cell culture enzyme immunoassay and a WNVKUN- specific monoclonal antibody. Probit analysis was used to determine mosquito susceptibility to infection. Infection, dissemination and transmission rates for selected days post-exposure were compared using Fisher’s exact test. Virus titers in bodies and saliva expectorates were compared using t-tests. Results There were few significant differences between the two virus strains in the susceptibility of Cx. annulirostris to infection, the kinetics of virus replication and the ability of this mosquito species to transmit either strain. Both strains were transmitted by Cx. annulirostris for the first time on day 5 post-exposure. The highest transmission rates (proportion of mosquitoes with virus detected in saliva) observed were 68% for WNVKUN2011 on day 12 and 72% for WNVKUN2009 on day 14. On days 12 and 14 post-exposure, significantly more WNVKUN2011 than WNVKUN2009 was expectorated by infected mosquitoes. Infection, dissemination and transmission rates of the two strains were not significantly different in Culex australicus. However, transmission rates and the amount of virus expectorated were significantly lower in Cx. australicus than Cx. annulirostris. Conclusions The higher amount of WNVKUN2011 expectorated by infected mosquitoes may be an indication that this virus strain is transmitted more efficiently by Cx. annulirostris compared to other WNVKUN strains. Combined with other factors, such as a convergence of abundant mosquito and wading bird populations, and mammalian and avian feeding behaviour by Cx. annulirostris, this may have contributed to the scale of the 2011 equine epidemic.

Temporal and environmental influences on the vocal behaviour of a nocturnal bird

Temporal and environmental variation in vocal activity can provide information on avian behaviour and call function not available to short-term experimental studies. Intersexual differences in this variation can provide insight into selection effects. Yet factors influencing vocal behaviour have not been assessed in many birds, even those monitored by acoustic methods. This applies to the New Zealand kiwi (Apterygidae), for which call censuses are used extensively in conservation monitoring, yet which have poorly understood acoustic ecology. We investigated little spotted kiwi Apteryx owenii vocal behaviour over 3 yr, measuring influences on vocal activity in both sexes from time of night, season, weather conditions and lunar cycle. We tested hypotheses that call rate variation reflects call function, foraging efficiency, historic predation risk and variability in sound transmission, and that there are inter-sexual differences in call function. Significant seasonal variation showed that vocalisations were important in kiwi reproduction, and inter-sexual synchronisation of call rates indicated that contact, pair-bonding or resource defence were key functions. All weather variables significantly affected call rates, with elevated calling during increased humidity and ground moisture indicating a relation between vocal activity and foraging conditions. A significant decrease in calling activity on cloudy nights, combined with no moonlight effect, suggests an impact of light pollution in this species. These influences on vocal activity provide insight into kiwi call function, have direct consequences for conservation monitoring of kiwi, and have wider implications in understanding vocal behaviour in a range of nocturnal birds

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Background The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk–outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990–2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8–58·5) of deaths and 41·6% (40·1–43·0) of DALYs. Risks quantified account for 87·9% (86·5–89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.

Role of pharmacists in collaborative care of travellers with chronic conditions

We refer to a paper recently published in the Journal of travel Medicine and Infectious Disease where clinicians have been shown to have in have many questions related to travellers to multiple destinations, going for prolonged duration of travel, with chronic medical conditions, and potential drug interactions.[1] This study highlighted the inadequacy of available information sources to resolve the wide range of different medical issues for travellers. In addition, the study also highlighted the significance of collaboration in travel health...

Numerical modelling of deformation behaviour of red blood cells in microvessels using the coupled SPH-DEM method

This thesis developed an advanced computational model to investigate the motion and deformation properties of red blood cells in capillaries. The novel model is based on the meshfree particle methods and is capable of modelling the large deformation of red blood cells moving through blood vessels. The developed model was employed to simulate the deformation behaviour of healthy and malaria infected red blood cells as well as the motion of red blood cells in stenosed capillaries.

Development of immunotherapies and vaccines against visceral leishmaiasis

Visceral leishmaniasis (VL) is a chronic parasitic disease prevalent in tropical and sub- tropical countries. This study focused on the development of immune-based therapy with immune checkpoint inhibitors and/or activators, as well as cytokines as a way to treat VL either alone or in combination with conventional drugs. Since many chronic infectious diseases share mechanisms of immune suppression, these findings have broader implications for other infectious diseases, such as HIV, tuberculosis and malaria.

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.

Disease control and management

Globally, the main contributors to morbidity and mortality are chronic conditions, including cardiovascular disease and diabetes. Chronic disease is costly and partially avoidable, with around 60% of deaths and nearly 50% of the global disease burden attributable to these conditions. By 2020, chronic illnesses will likely be the leading cause of disability worldwide. Existing healthcare systems that focus on acute episodic health conditions, both national and international, cannot address the worldwide transition to chronic illness; nor are they appropriate for the ongoing care and management of those already dealing with chronic diseases. As such, chronic disease management requires integrated approaches that incorporate interventions targeted at both individuals and populations, and emphasise the shared risk factors of different conditions. International and Australian strategic planning documents articulate similar elements to manage chronic disease, including the need for aligning sectoral policies for health, forming partnerships, and engaging communities in decision-making. Infectious diseases are also a common and significant contributor to ill health throughout the world. In many countries, this impact has been minimised by the combined efforts of preventative health measures and improved treatment methods. However, in low-income countries, infectious diseases remain the dominant cause of death and disability. The World Health Organization (WHO) estimates that infectious diseases (including respiratory infections) still account for around 23% (or around 14 million) of all deaths each year, and result in over 4.6 billion episodes of diarrhoeal disease and 243 million cases of malaria each year (Lozano et al. 2012, WHO 2009). In addition to the high level of mortality, infectious diseases disable many hundreds of millions of people each year, mainly in developing countries, with the global burden of disease from infectious diseases estimated to be around 300 million DALYs (disability-adjusted life years) (WHO 2012). The aim of this chapter is to outline the impact that infectious diseases and chronic diseases have on the health of the community, describe the public health strategies used to reduce the burden of those diseases, and discuss the historic and emerging disease risks to public health. This chapter examines the comprehensive approaches implemented to prevent both chronic and infectious diseases, and to manage and care for communities with these conditions.