The power of effective study design in animal experimentation: Exploring the statistical and ethical implications of asking multiple questions of a data set.

One of the chief advantages of using highly standardised biological models including model organisms is that multiple variables can be precisely controlled so that the variable of interest is more easily studied. However, such an approach often obscures effects in sub-populations resulting from natural population heterogeneity. Efforts to expand our fundamental understanding of multiple sub-populations are in progress. However, such stratified or personalised approaches require fundamental modifications of our usual study designs that should be implemented in Brain, Behavior and Immunity (BBI) research going forward. Here we explore the statistical feasibility of asking multiple questions (including incorporating sex) within the same experimental cohort using statistical simulations of real data. We illustrate and discuss the large explosion in sample numbers necessary to detect effects with appropriate power for every additional question posed using the same data set. This exploration highlights the strong likelihood of type II errors (false negatives) for standard data and type I errors when dealing with complex genomic data, where studies are too under-powered to appropriately test these interactions. We show this power may differ for males and females in high throughput data sets such as RNA sequencing. We offer a rationale for the use of alternative experimental and statistical strategies based on interdisciplinary insights and discuss the real-world implications of increasing the complexities of our experimental designs, and the implications of not attempting to alter our experimental designs going forward.

Neoliberalism and Indigenous oral health inequalities: a global perspective.

Neoliberalism is the dominant ideology underpinning the operation of many governments. Its tenets include policies of economic liberalization such as privatization, deregulation, free trade and reduced public expenditures on infrastructure and social services. Champions of neoliberalism claim that expansion of global trade has rescued millions from abject poverty and that direct foreign investment successfully transfers technology to developing economies. However, critics have urged governments to pay greater attention to how neoliberalism shapes population health. Indigenous populations experience inequalities in ways that are unique and distinct from the experiences of other marginalised groups. This is largely due to colonial influences that have resulted in sustained loss of lands, identity, languages and the control to live life in a traditional, cultural way that is meaningful. Oral health is simultaneously a reflection of material circumstances, structural inequities and access to health services. Indigenous populations carry a disproportionate burden of oral health inequalities at a global level. In this commentary, we contend that neoliberalism has overwhelmingly contributed to these inequities in three ways: (1) increased dominance of transnational corporations; (2) privatization of health and; (3) the neoliberal emphasis on personal responsibility.

Specific unwillingness to donate eyes: the impact of disfigurement, knowledge and procurement on corneal donation.

Although willingness, attitudes and beliefs surrounding solid-organ donation have been extensively investigated, much less is known about corneal donation. Despite evidence that a substantial number of families who agree to multiorgan donation also specifically refuse corneal donation, it is unclear why this occurs and what can be done to increase rates of corneal donation. We conducted a survey of 371 Australian adults regarding their views on corneal donation. Although willingness to donate corneas generally reflected a person's willingness to donate all of one's organs, unwillingness to donate corneas appeared to be due to other factors. Specifically, decisions not to donate appear to be driven by a range of concerns surrounding disfigurement. The survey also provides eye banks with reassurance about the acceptability of whole globe procurement, and recognition that research into blindness is a highly valued part of corneal donation. Finally, the survey identifies that many individuals see benefit in having their family engaged in the decision-making process, suggesting that decisions about donation are more complex than a simple appeal to the autonomy of the deceased.

Direct-to-consumer advertising under the radar: the need for realistic drugs policy in Australia.

Direct-to-consumer advertising of prescription medicines (DTCA-PM) is currently banned in Australia. DTCA-PM is thought to increase health-care costs by increasing demand for drugs that are both expensive and potentially harmful. However, DTCA-PM is occurring in Australia despite the current prohibition. We argue that successful regulation of the practice has been undermined as a result of changes brought about by the ongoing communications revolution, the increasing centrality of patient choice in medical decision-making and the impossibility of drawing and maintaining a sharp distinction between information and advertising. The prohibition is further threatened by recent international trade agreements. These factors make DTCA-PM inevitable and legislative and professional bodies need to acknowledge this to create a more effective health-care policy.

Psychosocial and ethical issues in surgical approaches to end-stage lung disease.

Heart-lung transplantation became a treatment option for end-stage lung parenchymal and vascular disease in 1981. Although many advances have occurred in the field surrounding donor selection, allograft preservation, surgical techniques, immunosuppression, and rejection and infection treatments, a shortage of cadaveric donors continues. This results in increased waiting times for the candidates, which in itself introduces an array of physical and psychological issues that must be addressed before transplant. This article examines the psychological factors evident in this period. In addition, ethical issues related to the allocation system and their impact on organ availability and, therefore, the time spent waiting for a lung transplant are presented.

Establishing the role of pre-implantation genetic diagnosis with human leucocyte antigen typing: what place do "saviour siblings" have in paediatric transplantation?

BACKGROUND: Not all children in need of a haematopoietic stem cell transplant have a suitable relative or unrelated donor available. Recently, in vitro fertilisation (IVF) with pre-implantation genetic diagnosis (PGD) for human leucocyte antigen (HLA) tissue typing has been used to selectively transfer an IVF embryo in order to produce a child who may provide umbilical cord blood for transplantation to an ill sibling. Such children are sometimes called "saviour siblings". OBJECTIVE: To examine the published clinical and epidemiological evidence relevant to the use of this technology, with the aim of clarifying those situations where IVF and PGD for HLA typing should be discussed with parents of an ill child. DESIGN: A critical analysis of published literature on comparative studies of umbilical cord blood versus other sources of stem cells for transplantation; comparative studies of matched unrelated donor versus matched related donor transplantation; and the likelihood of finding an unrelated stem cell donor. CONCLUSION: IVF and PGD for HLA typing is only applicable when transplantation is non-urgent and parents are of reproductive age. Discussions regarding this technology may be appropriate where no suitable related or unrelated donor is available for a child requiring a transplant, or where no suitable related donor is available and transplantation is only likely to be entertained with a matched sibling donor. Discussion may also be considered in the management of any child lacking a matched related donor who requires a non-urgent transplant or may require a transplant in the future.

Consent in crisis: the need to reconceptualize consent to tissue banking research.

The issues surrounding consent to tissue banking research in Australia are complex and have created a forum of intense debate, thus providing a window of opportunity to critically appraise and challenge standard models of consent for research in general and for tissue banking research in particular. The usual practical difficulties associated with meeting the criteria for valid consent to research (including adequate information provision and voluntariness) are amplified in the case of tissue banking research. A number of models, based on widely accepted ethical principles, have been proposed to improve the process of obtaining consent to tissue banking research, all of which assume that the consent of individual tissue donors is needed to meet the criteria for valid consent. Feminist and communitarian theories use many of the same criteria for valid consent but interpret these criteria differently and de-emphasize the importance of individual autonomy as the central criterion for valid consent. An enriched model of consent incorporating feminist and communitarian ideas could satisfy the currently accepted criteria for valid consent while also furthering a broader range of community values.