Access to essential medicines: Public health and international law

Historically, there have been intense conflicts over the ownership and exploitation of pharmaceutical drugs and diagnostic tests dealing with infectious diseases. Throughout the 1980’s, there was much scientific, legal, and ethical debate about which scientific group should be credited with the discovery of the human immunodeficiency virus, and the invention of the blood test devised to detect antibodies to the virus. In May 1983, Luc Montagnier, Françoise Barré-Sinoussi, and other French scientists from the Pasteur Institute in Paris, published a paper in Science, detailing the discovery of a virus called lymphadenopathy (LAV). A scientific rival, Robert Gallo of the National Cancer Institute, identified the AIDS virus and published his findings in the May 1984 issue of Science. In May 1985, the United States Patent and Trademark Office awarded the American patent for the AIDS blood test to Gallo and the Department of Health and Human Services. In December 1985, the Institut Pasteur sued the Department of Health and Human Services, contending that the French were the first to identify the AIDS virus and to invent the antibody test, and that the American test was dependent upon the French research. In March 1987, an agreement was brokered by President Ronald Reagan and French Prime Minister Jacques Chirac, which resulted in the Department of Health and Human Services and the Institut Pasteur sharing the patent rights to the blood test for AIDS. In 1992, the Federal Office of Research Integrity found that Gallo had committed scientific misconduct, by falsely reporting facts in his 1984 scientific paper. A subsequent investigation by the National Institutes of Health, the United States Congress, and the US attorney-general cleared Gallo of any wrongdoing. In 1994, the United States government and French government renegotiated their agreement regarding the AIDS blood test patent, in order to make the distribution of royalties more equitable... The dispute between Luc Montagnier and Robert Gallo was not an isolated case of scientific rivalry and patent races. It foreshadowed further patent conflicts over research in respect of HIV/AIDS. Michael Kirby, former Justice of the High Court of Australia diagnosed a clash between two distinct schools of philosophy - ‘scientists of the old school... working by serendipity with free sharing of knowledge and research’, and ‘those of the new school who saw the hope of progress as lying in huge investments in scientific experimentation.’ Indeed, the patent race between Robert Gallo and Luc Montagnier has been a precursor to broader trade disputes over access to essential medicines in the 1990s and 2000s. The dispute between Robert Gallo and Luc Montagnier captures in microcosm a number of themes of this book: the fierce competition for intellectual property rights; the clash between sovereign states over access to medicines; the pressing need to defend human rights, particularly the right to health; and the need for new incentives for research and development to combat infectious diseases as both an international and domestic issue.

Damned to fame: The moral rights of the Beckett estate

The Company B production of Samuel Beckett's Waiting for Godot raises important questions about copyright law, moral rights, and dramatic works. The playwright's nephew and executor, Edward Beckett, threatened to bring a legal action against the Sydney company for breach of contract on the grounds that unauthorised music appeared in the production. The Company B production denied that the contract made any such express provisions. The director Neil Armfield complained: 'In coming here with its narrow prescriptions, its dead controlling hand, the Beckett estate seems to me to be the enemy of art'. In the biography Damned to fame, James Knowlson documents a number of other proceedings taken by Beckett and his agents to control the productions of his work: 'He was often represented as a tyrannical figure, an arch-controller of his work, ready to unleash fiery thunderbolts onto the head of any bold, innovative director, unwilling to follow his text and stage directions to the last counted dot and precisely timed pause.' However, Knowlson notes that Beckett was inconsistent in his willingness to use legal action: 'It made a tremendous difference if he liked and respected the persons involved or if he had been able to listen to their reasons for wanting to attempt something highly innovative or even slightly different'. Famously, in 1988, Beckett brought legal action against a Dutch theatre company, which wanted to stage a production of Waiting for Godot, with women acting all the roles. His lawyer argued that the integrity of the text was violated because actresses were substituted for the male actors asked for in the text. The judge in the Haarlem court ruled that the integrity of the play had not been violated, because the performance showed fidelity to the dialogue and the stage directions of the play. By contrast, in 1992, a French court held a stage director was liable for an infringement of Beckett's moral right of integrity because the director had staged Waiting for Godot with the two lead roles played by women. In 1998, a United States production of Waiting for Godot with a racially mixed cast attracted legal threats amid accusations it had 'injected race into the play'. In the 2000 New York Fringe Festival, a company made light of this ongoing conflict between the Beckett estate and artistic directors. The work was entitled: The complete lost works of Samuel Beckett as found in an envelope (partially burned) in a dustbin in Paris labelled 'Never to be performed. Never. Ever. EVER! Or I'll sue! I'LL SUE FROM THE GRAVE!'. The plot concerned a fight between three producers and the Beckett estate. In the wake of such disputes, Beckett and later his estate sought to tighten production contracts to state that no additions, omissions or alterations should be made to the text of the play or the stage directions and that no music, special effects or other supplements should be added without prior consent.

Designing a quality health information system: Case study analysis of maternal and child health in Papua New Guinea

Papua New Guinea (PNG) is facing what must seem like an insurmountable challenge to deliver quality healthcare servicesfor women living in both rural and urban areas. Glo bal governing bodies and donor agencies including WHO and UN have indicated that PNG does not have an appropriate health information system. Although there are some systems in place, to date, little research has been conducted on improving or resolving the data integrity and integration issues of the existing health information systems and automating the capture of women and newborns information in PNG. This current research study concentrates on the adoption of eHealth, as an innovative tool to strengthen the health information systems in PNG to meet WHO standards. The research targets maternal and child health focussing on child birth records asan exemplar...

Novel protective covering to enhance concrete resistance against projectile impact

A novel protective covering with a layered and staggered structure was proposed to protect concrete against projectile impact. Experimental study was conducted to investigate the ballistic behaviour of the concrete targets against 12.7 mm armour-piercing incendiary projectile at velocities ranging from 537.7 to 596.5 m/s. The results showed that the concrete targets with protective covering exhibited superior integrity with no damage on the distal surface, whereas the concrete targets without protective covering were fractured with penetrating cracks throughout the thickness of the target. Moreover, the protected concrete targets displayed significantly reduced penetration depth compared with the concrete targets without protective covering. The protective covering with epoxy adhesive interlayers had a bigger protection factor than that with silicone sealant interlayers, but the former suffered more severe damage than the latter.

Analysis of one-pass block cipher based authenticated encryption schemes

This project analyses and evaluates the integrity assurance mechanisms used in four Authenticated Encryption schemes based on symmetric block ciphers. These schemes are all cross chaining block cipher modes that claim to provide both confidentiality and integrity assurance simultaneously, in one pass over the data. The investigations include assessing the validity of an existing forgery attack on certain schemes, applying the attack approach to other schemes and implementing the attacks to verify claimed probabilities of successful forgeries. For these schemes, the theoretical basis of the attack was developed, the attack algorithm implemented and computer simulations performed for experimental verification.

Adopting healthcare big data in Sri Lankan healthcare sector

The concept of big data has already outperformed traditional data management efforts in almost all industries. Other instances it has succeeded in obtaining promising results that provide value from large-scale integration and analysis of heterogeneous data sources for example Genomic and proteomic information. Big data analytics have become increasingly important in describing the data sets and analytical techniques in software applications that are so large and complex due to its significant advantages including better business decisions, cost reduction and delivery of new product and services [1]. In a similar context, the health community has experienced not only more complex and large data content, but also information systems that contain a large number of data sources with interrelated and interconnected data attributes. That have resulted in challenging, and highly dynamic environments leading to creation of big data with its enumerate complexities, for instant sharing of information with the expected security requirements of stakeholders. When comparing big data analysis with other sectors, the health sector is still in its early stages. Key challenges include accommodating the volume, velocity and variety of healthcare data with the current deluge of exponential growth. Given the complexity of big data, it is understood that while data storage and accessibility are technically manageable, the implementation of Information Accountability measures to healthcare big data might be a practical solution in support of information security, privacy and traceability measures. Transparency is one important measure that can demonstrate integrity which is a vital factor in the healthcare service. Clarity about performance expectations is considered to be another Information Accountability measure which is necessary to avoid data ambiguity and controversy about interpretation and finally, liability [2]. According to current studies [3] Electronic Health Records (EHR) are key information resources for big data analysis and is also composed of varied co-created values [3]. Common healthcare information originates from and is used by different actors and groups that facilitate understanding of the relationship for other data sources. Consequently, healthcare services often serve as an integrated service bundle. Although a critical requirement in healthcare services and analytics, it is difficult to find a comprehensive set of guidelines to adopt EHR to fulfil the big data analysis requirements. Therefore as a remedy, this research work focus on a systematic approach containing comprehensive guidelines with the accurate data that must be provided to apply and evaluate big data analysis until the necessary decision making requirements are fulfilled to improve quality of healthcare services. Hence, we believe that this approach would subsequently improve quality of life.

The doctrine of necessity and the detention and restraint of people with intellectual impairment: Is there any justification?

In Australia, the legal basis for the detention and restraint of people with intellectual impairment is ad hoc and unclear. There is no comprehensive legal framework that authorises and regulates the detention of, for example, older people with dementia in locked wards or in residential aged care, people with disability in residential services or people with acquired brain injury in hospital and rehabilitation services. This paper focuses on whether the common law doctrine of necessity (or its statutory equivalents) should have a role in permitting the detention and restraint of people with disabilities. Traditionally, the defence of necessity has been recognised as an excuse, where the defendant, faced by a situation of imminent peril, is excused from the criminal or civil liability because of the extraordinary circumstances they find themselves in. In the United Kingdom, however, in In re F (Mental Patient: Sterilisation) and R v Bournewood Community and Mental Health NHS Trust, ex parte L, the House of Lords broadened the defence so that it operated as a justification for treatment, detention and restraint outside of the emergency context. This paper outlines the distinction between necessity as an excuse and as a defence, and identifies a number of concerns with the latter formulation: problems of democracy, integrity, obedience, objectivity and safeguards. Australian courts are urged to reject the United Kingdom approach and retain an excuse-based defence, as the risks of permitting the essentially utilitarian model of necessity as a justification are too great.

Medical Data Access Accountability in EHR Systems, A Practical Perspective

The world has experienced a large increase in the amount of available data. Therefore, it requires better and more specialized tools for data storage and retrieval and information privacy. Recently Electronic Health Record (EHR) Systems have emerged to fulfill this need in health systems. They play an important role in medicine by granting access to information that can be used in medical diagnosis. Traditional systems have a focus on the storage and retrieval of this information, usually leaving issues related to privacy in the background. Doctors and patients may have different objectives when using an EHR system: patients try to restrict sensible information in their medical records to avoid misuse information while doctors want to see as much information as possible to ensure a correct diagnosis. One solution to this dilemma is the Accountable e-Health model, an access protocol model based in the Information Accountability Protocol. In this model patients are warned when doctors access their restricted data. They also enable a non-restrictive access for authenticated doctors. In this work we use FluxMED, an EHR system, and augment it with aspects of the Information Accountability Protocol to address these issues. The Implementation of the Information Accountability Framework (IAF) in FluxMED provides ways for both patients and physicians to have their privacy and access needs achieved. Issues related to storage and data security are secured by FluxMED, which contains mechanisms to ensure security and data integrity. The effort required to develop a platform for the management of medical information is mitigated by the FluxMED's workflow-based architecture: the system is flexible enough to allow the type and amount of information being altered without the need to change in your source code.

Decellularized periodontal ligament cell sheets with recellularization potential

The periodontal ligament is the key tissue facilitating periodontal regeneration. This study aimed to fabricate decellularized human periodontal ligament cell sheets for subsequent periodontal tissue engineering applications. The decellularization protocol involved the transfer of intact human periodontal ligament cell sheets onto melt electrospun polycaprolactone membranes and subsequent bi-directional perfusion with NH4OH/Triton X-100 and DNase solutions. The protocol was shown to remove 92% of DNA content. The structural integrity of the decellularized cell sheets was confirmed by a collagen quantification assay, immunostaining of human collagen type I and fibronectin, and scanning electron microscopy. ELISA was used to demonstrate the presence of residual basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) in the decellularized cell sheet constructs. The decellularized cell sheets were shown to have the ability to support recellularization by allogenic human periodontal ligament cells. This study describes the fabrication of decellularized periodontal ligament cell sheets that retain an intact extracellular matrix and resident growth factors and can support repopulation by allogenic cells. The decellularized hPDL cell sheet concept has the potential to be utilized in future "off-the-shelf" periodontal tissue engineering strategies.

Dependence of light attenuation and backscattering on collagen concentration and chondrocyte density in agarose scaffolds

Optical coherence tomography (OCT) has been applied for high resolution imaging of articular cartilage. However, the contribution of individual structural elements of cartilage on OCT signal has not been thoroughly studied. We hypothesize that both collagen and chondrocytes, essential structural components of cartilage, act as important light scatterers and that variation in their concentrations can be detected by OCT through changes in backscattering and attenuation. To evaluate this hypothesis, we established a controlled model system using agarose scaffolds embedded with variable collagen concentrations and chondrocyte densities. Using OCT, we measured the backscattering coefficient (µb) and total attenuation coefficient (µt) in these scaffolds. Along our hypothesis, light backscattering and attenuation in agarose were dependent on collagen concentration and chondrocyte density. Significant correlations were found between µt and chondrocyte density (ρ = 0.853, p < 0.001) and between µt and collagen concentration (ρ = 0.694, p < 0.001). µb correlated significantly with chondrocyte density (ρ = 0.504, p < 0.001) but not with collagen concentration (ρ = 0.103, p = 0.422) of the scaffold. Thus, quantitation of light backscattering and, especially, attenuation could be valuable when evaluating the integrity of soft tissues, such as articular cartilage with OCT.

Pancreatic islet basement membrane loss and remodeling after mouse islet isolation and transplantation: Impact for allograft rejection

The isolation of islets by collagenase digestion can cause damage and impact the efficiency of islet engraftment and function. In this study, we assessed the basement membranes (BMs) of mouse pancreatic islets as a molecular biomarker for islet integrity, damage after isolation, and islet repair in vitro as well as in the absence or presence of an immune response after transplantation. Immunofluorescence staining of BM matrix proteins and the endothelial cell marker platelet endothelial cell adhesion molecule-1 (PECAM-1) was performed on pancreatic islets in situ, isolated islets, islets cultured for 4 days, and islet grafts at 3-10 days posttransplantation. Flow cytometry was used to investigate the expression of BM matrix proteins in isolated islet β-cells. The islet BM, consisting of collagen type IV and components of Engelbreth-Holm-Swarm (EHS) tumor laminin 111, laminin α2, nidogen-2, and perlecan in pancreatic islets in situ, was completely lost during islet isolation. It was not reestablished during culture for 4 days. Peri- and intraislet BM restoration was identified after islet isotransplantation and coincided with the migration pattern of PECAM-1(+) vascular endothelial cells (VECs). After islet allotransplantation, the restoration of VEC-derived peri-islet BMs was initiated but did not lead to the formation of the intraislet vasculature. Instead, an abnormally enlarged peri-islet vasculature developed, coinciding with islet allograft rejection. The islet BM is a sensitive biomarker of islet damage resulting from enzymatic isolation and of islet repair after transplantation. After transplantation, remodeling of both peri- and intraislet BMs restores β-cell-matrix attachment, a recognized requirement for β-cell survival, for isografts but not for allografts. Preventing isolation-induced islet BM damage would be expected to preserve the intrinsic barrier function of islet BMs, thereby influencing both the effector mechanisms required for allograft rejection and the antirejection strategies needed for allograft survival.

Nanoindentation study of the mechanical behavior of TiO2 nanotube arrays

Titanium dioxide (TiO2) nanotube arrays are attracting increasing attention for use in solar cells, lithium-ion batteries, and biomedical implants. To take full advantage of their unique physical properties, such arrays need to maintain adequate mechanical integrity in applications. However, the mechanical performance of TiO2 nanotube arrays is not well understood. In this work, we investigate the deformation and failure of TiO2 nanotube arrays using the nanoindentation technique. We found that the load–displacement response of the arrays strongly depends on the indentation depth and indenter shape. Substrate-independent elastic modulus and hardness can be obtained when the indentation depth is less than 2.5% of the array height. The deformation mechanisms of TiO2 nanotube arrays by Berkovich and conical indenters are closely associated with the densification of TiO2 nanotubes under compression. A theoretical model for deformation of the arrays under a largeradius conical indenter is also proposed.

Tumor-associated mutations inO6-methylguanine DNA-methyltransferase (MGMT) reduce DNA repair functionality

MGMT is the primary vehicle for cellular removal of alkyl lesions from the O-6 position of guanine and the O-4 position of thymine. While key to the maintenance of genomic integrity, MGMT also removes damage induced by alkylating chemotherapies, inhibiting the efficacy of cancer treatment. Germline variants of human MGMT are well-characterized, but somatic variants found in tumors were, prior to this work, uncharacterized. We found that MGMT G132R, from a human esophageal tumor, and MGMT G156C, from a human colorectal cancer cell line, are unable to rescue methyltransferase-deficient Escherichia coli as well as wild type (WT) human MGMT after treatment with a methylating agent. Using pre-steady state kinetics, we biochemically characterized these variants as having a reduced rate constant. G132R binds DNA containing an O6-methylguanine lesion half as tightly as WT MGMT, while G156C has a 40-fold decrease in binding affinity for the same damaged DNA versus WT. Mammalian cells expressing either G132R or G156C are more sensitive to methylating agents than mammalian cells expressing WT MGMT. G132R is slightly resistant to O6-benzylguanine, an inhibitor of MGMT in clinical trials, while G156C is almost completely resistant to this inhibitor. The impared functionality of expressed variants G132R and G156C suggests that the presence of somatic variants of MGMT in a tumor could impact chemotherapeutic outcomes.

Evaluation framework to assess orthopaedic procedures

Introduction & aims The demand for evidence of efficacy of treatments in general and orthopaedic surgical procedures in particular is ever increasing in Australia and worldwide. The aim of this study is to share the key elements of an evaluation framework recently implemented in Australia to determine the efficacy of bone-anchored prostheses. Method The proposed evaluation framework to determine the benefit and harms of bone-anchored prostheses for individuals with limb loss was extracted from a systematic review of the literature including seminal studies focusing on clinical benefits and safety of procedures involving screw-type implant (e.g., OPRA) and press-fit fixations (e.g., EEFT, ILP, OPL). [1-64] Results The literature review highlighted that a standard and replicable evaluation framework should focus on: • The clinical benefits with a systematic recording of health-related quality of life (e.g., SF-26, Q-TFA), mobility predictor (e.g., AMPRO), ambulation abilities (e.g., TUG, 6MWT), walking abilities (e.g., characteristic spatio-temporal) and actual activity level at baseline and follow-up post Stage 2 surgery, • The potential harms with systematic recording of residuum care, infection, implant stability, implant integrity, injuries (e.g., falls) after Stage 1 surgery. There was a general consensus around the instruments to monitor most of the benefits and harms. The benefits could be assessed using a wide spectrum of complementary assessments ranging from subjective patient self-reporting to objective measurements of physical activity. However, this latter was assessed using a broad range of measurements (e.g., pedometer, load cell, energy consumption). More importantly, the lack of consistent grading of infections was sufficiently noticeable to impede cross-fixation comparisons. Clearly, a more universal grading system is needed. Conclusions Investigators are encouraged to implement an evaluation framework featuring the domains and instruments proposed above using a single database to facilitate robust prospective studies about potential benefits and harms of their procedure. This work is also a milestone in the development of national and international clinical outcome registries.

'But I've never sent them any personal details apart from my driver's licence number...': Exploring seniors' attitudes towards identity crime

Identity crime is argued to be one of the most significant crime problems of today. This paper examines identity crime, through the attitudes and practices of a group of seniors in Queensland, Australia. It examines their own actions towards the protection of their personal data in response to a fraudulent email request. Applying the concept of a prudential citizen (as one who is responsible for self-regulating their behaviour to maintain the integrity of one’s identity) it will be argued that seniors often expose identity information through their actions. However, this is demonstrated to be the result of flawed assumptions and misguided beliefs over the perceived risk and likelihood of identity crime, rather than a deliberate act. This paper concludes that to protect seniors from identity crime, greater awareness of appropriate risk-management strategies towards disclosure of their personal details is required to reduce their inadvertent exposure to identity crime.