A cross-sectional study of the first two years of mandatory training for doctors participating in voluntary assisted dying.

OBJECTIVES: Voluntary assisted dying (VAD) was legalized in Victoria, Australia, in June 2019. Victoria was the first jurisdiction in the world to require doctors to undertake training before providing VAD. This study examines data from doctors who completed the mandatory training in the first 2 years of the VAD system's operation (up to 30 June 2021). It describes the doctors who are undertaking VAD training, their post-training attitudes toward VAD participation, and their experiences of the mandatory training. METHODS: Through the online training, doctors completed a short demographic survey and undertook formal assessment of knowledge (90% pass mark). They also were invited to complete an optional survey evaluating the training. RESULTS: In total, 289 doctors passed the training, most commonly males (56%) aged 36-65 years (82%) from an urban location (72%). Most were more than 10 years post fellowship (68%) and practising as general practitioners (51%) or medical oncologists (16%). The training most commonly took 6 h (range 2 h to over 9 h). Most doctors passed the assessment at the first (65%) or second (19%) attempt. Almost all participants (97%) found the training helpful or very helpful and most reported being confident or very confident in their knowledge (93%) and application (88%) of the VAD legislation. SIGNIFICANCE OF RESULTS: Doctors reported the training was helpful and improved their confidence in knowing the law and applying it in clinical practice. The profile of trained doctors (particularly their location and specialty) suggests continued growth of participating doctors is needed to facilitate patient access to VAD. It is important that this safeguard does not discourage doctors' participation.

Clinical supervision in general practice training: the interweaving of supervisor, trainee and patient entrustment with clinical oversight, patient safety and trainee learning.

Australian general practice trainees typically consult with patients from their first week of training, seeking in-consultation supervisory assistance only when not sufficiently confident to complete patient consultations independently. Trainee help-seeking plays a key role in supervisor oversight of trainee consultations. This study used focus groups and interviews with general practice supervisors to explore their approaches to trainee help-seeking and in-consultation supervision. Supervisor approaches are discussed under three themes: establishing a help-seeking culture; perceptions of in-consultation assistance required; and scripts for help provision. Within these themes, three interwoven entrustment processes were identified: supervisor entrustment; trainee self-entrustment; and 'patient entrustment' (patient confidence in the trainee's clinical management). Entrustment appears to develop rapidly, holistically and informally in general practice training, partly in response to workflow pressure and time constraints. Typical supervisor scripts and etiquette for help-provision involve indirect, soft correction strategies to build trainee self-entrustment. These scripts appear to be difficult to adapt appropriately to under-performing trainees. Importantly, supervisor scripts also promote patient entrustment, increasing the likelihood of patients returning to the trainee and training practice for subsequent review, which is a major mechanism for ensuring patient safety in general practice. Theories of entrustment in general practice training must account for the interplay between supervisor, trainee and patient entrustment processes, and work-related constraints. Gaps between entrustment as espoused in theory, and entrustment as enacted, may suggest limitations of entrustment theory when extended to the general practice context, and/or room for improvement in the oversight of trainee consultations in general practice training.

With a grain of salt? Supervisor credibility and other factors influencing trainee decisions to seek in-consultation assistance: a focus group study of Australian general practice trainees.

BACKGROUND: 'Ad hoc' help-seeking by trainees from their supervisors during trainee consultations is important for patient safety, and trainee professional development. We explored trainee objectives and activities in seeking supervisor assistance, and trainee perceptions of the outcomes of this help-seeking (including the utility of supervisor responses). METHODS: Focus groups with Australian general practice trainees were undertaken. All data was audio-recorded and transcribed, coded using in-vivo and descriptive codes, and analysed by the constant comparison of provisional interpretations and themes with the data. Findings are reported under the over-arching categories of help-seeking objectives, activities and outcomes. RESULTS: Early in their general practice placements trainees needed information about practice facilities, and the "complex maze" of local patient resources and referral preferences: some clinical presentations were also unfamiliar, and many trainees were unaccustomed to making patient management decisions. Subsequent help-seeking was often characterised informally as "having a chat" or "getting a second opinion" so as not to "miss anything" when trainees were "not 100% sure". Trainees emphasised the importance of being (and demonstrating that they were) clinically safe. Workflow constraints, and supervisory and doctor-patient relationships, had a powerful influence on trainee help-seeking activities. An etiquette for providing help in front of patients was described. Trainees assessed the credibility of supervisors based on their approach to risk and their clinical expertise in the relevant area. Several trainees reported reservations about their supervisor's advice on occasions. CONCLUSION: A trainee's subsequent help-seeking is strongly influenced by how their supervisor responds when their help is sought. Trainees prefer to seek help from credible supervisors who respond promptly and maintain trainee 'face' in front of patients. Trainees learn through help-seeking to make their own clinical decisions but may remain uncertain about professional and societal expectations, and curious about how other general practitioners practise. Trainees value opportunities throughout their training to observe expert general practice.

Ncoa3 functions as an essential Esrrb coactivator to sustain embryonic stem cell self-renewal and reprogramming.

Embryonic stem cell (ESC) pluripotency depends on a well-characterized gene regulatory network centered on Oct4, Sox2, and Nanog. In contrast, little is known about the identity of the key coregulators and the mechanisms by which they may potentiate transcription in ESCs. Alongside core transcription factors, the orphan nuclear receptor Esrrb (estrogen-related receptor ß) is vital for the maintenance of ESC identity and furthermore is uniquely associated with the basal transcription machinery. Here, we show that Ncoa3, an essential coactivator, is required to mediate Esrrb function in ESCs. Ncoa3 interacts with Esrrb via its ligand-binding domain and bridges Esrrb to RNA polymerase II complexes. Functionally, Ncoa3 is critical for both the induction and maintenance of pluripotency. Through chromatin immunoprecipitation (ChIP) sequencing and microarray experiments, we further demonstrate that Ncoa3 shares overlapping gene regulatory functions with Esrrb and cooperates genome-wide with the Oct4-Sox2-Nanog circuitry at active enhancers to up-regulate genes involved in self-renewal and pluripotency. We propose an integrated model of transcriptional and coactivator control, mediated by Ncoa3, for the maintenance of ESC self-renewal and somatic cell reprogramming.

Doctors' perceptions of how resource limitations relate to futility in end-of-life decision making: a qualitative analysis.

OBJECTIVE: To increase knowledge of how doctors perceive futile treatments and scarcity of resources at the end of life. In particular, their perceptions about whether and how resource limitations influence end-of-life decision making. This study builds on previous work that found some doctors include resource limitations in their understanding of the concept of futility. SETTING: Three tertiary hospitals in metropolitan Brisbane, Australia. DESIGN: Qualitative study using in-depth, semistructured, face-to-face interviews. Ninety-six doctors were interviewed in 11 medical specialties. Transcripts of the interviews were analysed using thematic analysis. RESULTS: Doctors' perceptions of whether resource limitations were relevant to their practice varied, and doctors were more comfortable with explicit rather than implicit rationing. Several doctors incorporated resource limitations into their definition of futility. For some, availability of resources was one factor of many in assessing futility, secondary to patient considerations, but a few doctors indicated that the concept of futility concealed rationing. Doctors experienced moral distress due to the resource implications of providing futile treatment and the lack of administrative supports for bedside rationing. CONCLUSIONS: Doctors' ability to distinguish between futility and rationing would be enhanced through regulatory support for explicit rationing and strategies to support doctors' role in rationing at the bedside. Medical policies should address the distinction between resource limitations and futility to promote legitimacy in end-of-life decision making.

Australian Policies on "Futile" or "Non-beneficial" Treatment at the End of Life: A Qualitative Content Analysis.

A challenge in end-of-life care is requests by patients or their substitute decision-makers for treatment that doctors consider is "futile" or "non-beneficial". Concerns that these concepts are uncertain and subjective have led to calls for medical policies to clarify terminology and to provide procedural solutions to prevent and address disputes. This article provides a comprehensive analysis of how Australian medical guidelines and policies on withholding or withdrawing potentially life-sustaining treatment address futility. It demonstrates that while the concept is found throughout medical policies and guidelines, the terminology employed is inconsistent. There is also variability in the extent of guidance given about unilateral decision-making and mechanisms for dispute resolution. This is problematic, given that the question of further treatment can often only be determined in relation to the individual patient's goals and values. We conclude by advocating for the development of a unified policy approach to futile or non-beneficial treatment in Australia.

Gestational disruptions in metabolic rhythmicity of the liver, muscle, and placenta affect fetal size.

Maternal metabolic adaptations are essential for successful pregnancy outcomes. We investigated how metabolic gestational processes are coordinated, whether there is a functional link with internal clocks, and whether disruptions are related to metabolic abnormalities in pregnancy, by studying day/night metabolic pathways in murine models and samples from pregnant women with normally grown and large-for-gestational age infants. In early mouse pregnancy, expression of hepatic lipogenic genes was up-regulated and uncoupled from the hepatic clock. In late mouse pregnancy, rhythmicity of energy metabolism-related genes in the muscle followed the patterns of internal clock genes in this tissue, and coincided with enhanced lipid transporter expression in the fetoplacental unit. Diurnal triglyceride patterns were disrupted in human placentas from pregnancies with large-for-gestational age infants and this overlapped with an increase in BMAL1 expression. Metabolic adaptations in early pregnancy are uncoupled from the circadian clock, whereas in late pregnancy, energy availability is mediated by coordinated muscle-placenta metabolic adjustments linked to internal clocks. Placental triglyceride oscillations in the third trimester of human pregnancy are lost in large-for-gestational age infants and may be regulated by BMAL1. In summary, disruptions in metabolic and circadian rhythmicity are associated with increased fetal size, with implications for the pathogenesis of macrosomia.-Papacleovoulou, G., Nikolova, V., Oduwole, O., Chambers, J., Vazquez-Lopez, M., Jansen, E., Nicolaides, K., Parker, M., Williamson, C. Gestational disruptions in metabolic rhythmicity of the liver, muscle, and placenta affect fetal size.

Australian doctors' knowledge of and compliance with the law relating to end-of-life decisions: implications for LGBTI patients.

In most developed countries, competent patients have the legal right to refuse any medical treatment; Advance Care Planning mechanisms extend this right to non-competent patients. However, some groups, including lesbian, gay, bisexual, transgender and intersex (LGBTI) people, risk their wishes not being respected if they lose capacity, more than others. Little is known about medical practitioners' knowledge of, or attitudes to, the law in this area, especially in relation to LGBTI people, or how the law influences their decision-making. An Australian postal survey explored knowledge and attitudes of medical specialists to legal issues relating to withdrawing/ withholding life-sustaining treatment from adults without capacity. One scenario (the focus of this paper) asked which of four plausible substitute decision-makers, including a same-sex partner, had the legal authority to make such decisions. The overall response rate was 32% (867/2702). Less than one-third of respondents correctly identified the same-sex partner as the legally authorised decision-maker. LGBTI people face multiple obstacles to having their end-of-life wishes respected. Where healthcare providers are also ignorant of the partner's legal right to make such decisions, the problem is compounded. Improved legal education for clinicians and promotion of educational resources for members of the LGBTI community is needed.

Changes in LXR signaling influence early-pregnancy lipogenesis and protect against dysregulated fetoplacental lipid homeostasis.

Human pregnancy is associated with enhanced de novo lipogenesis in the early stages followed by hyperlipidemia during advanced gestation. Liver X receptors (LXRs) are oxysterol-activated nuclear receptors that stimulate de novo lipogenesis and also promote the efflux of cholesterol from extrahepatic tissues followed by its transport back to the liver for biliary excretion. Although LXR is recognized as a master regulator of triglyceride and cholesterol homeostasis, it is unknown whether it facilitates the gestational adaptations in lipid metabolism. To address this question, biochemical profiling, protein quantification, and gene expression studies were used, and gestational metabolic changes in T0901317-treated wild-type mice and Lxrab-/- mutants were investigated. Here, we show that altered LXR signaling contributes to the enhanced lipogenesis in early pregnancy by increasing the expression of hepatic Fas and stearoyl-CoA desaturase 1 (Scd1). Both the pharmacological activation of LXR with T0901317 and the genetic ablation of its two isoforms disrupted the increase in hepatic fatty acid biosynthesis and the development of hypertriglyceridemia during early gestation. We also demonstrate that absence of LXR enhances maternal white adipose tissue lipolysis, causing abnormal accumulation of triglycerides, cholesterol, and free fatty acids in the fetal liver. Together, these data identify LXR as an important factor in early-pregnancy lipogenesis that is also necessary to protect against abnormalities in fetoplacental lipid homeostasis.

The role of law in decisions to withhold and withdraw life-sustaining treatment from adults who lack capacity: a cross-sectional study.

OBJECTIVES: To determine the role played by law in medical specialists' decision-making about withholding and withdrawing life-sustaining treatment from adults who lack capacity, and the extent to which legal knowledge affects whether law is followed. DESIGN: Cross-sectional postal survey of medical specialists. SETTING: The two largest Australian states by population. PARTICIPANTS: 649 medical specialists from seven specialties most likely to be involved in end-of-life decision-making in the acute setting. MAIN OUTCOME MEASURES: Compliance with law and the impact of legal knowledge on compliance. RESULTS: 649 medical specialists (of 2104 potential participants) completed the survey (response rate 31%). Responses to a hypothetical scenario found a potential low rate of legal compliance, 32% (95% CI 28% to 36%). Knowledge of the law and legal compliance were associated: within compliers, 86% (95% CI 83% to 91%) had specific knowledge of the relevant aspect of the law, compared with 60% (95% CI 55% to 65%) within non-compliers. However, the reasons medical specialists gave for making decisions did not vary according to legal knowledge. CONCLUSIONS: Medical specialists prioritise patient-related clinical factors over law when confronted with a scenario where legal compliance is inconsistent with what they believe is clinically indicated. Although legally knowledgeable specialists were more likely to comply with the law, compliance in the scenario was not motivated by an intention to follow law. Ethical considerations (which are different from, but often align with, law) are suggested as a more important influence in clinical decision-making. More education and training of doctors is needed to demonstrate the role, relevance and utility of law in end-of-life care.

Comparing doctors' legal compliance across three Australian states for decisions whether to withhold or withdraw life-sustaining medical treatment: does different law lead to different decisions?

BACKGROUND: Law purports to regulate end-of-life care but its role in decision-making by doctors is not clear. This paper, which is part of a three-year study into the role of law in medical practice at the end of life, investigates whether law affects doctors' decision-making. In particular, it considers whether the fact that the law differs across Australia's three largest states - New South Wales (NSW), Victoria and Queensland - leads to doctors making different decisions about withholding and withdrawing life-sustaining treatment from adults who lack capacity. METHODS: A cross-sectional postal survey of the seven specialties most likely to be involved in end-of-life care in the acute setting was conducted between 18 July 2012 and 31 January 2013. The sample comprised all medical specialists in emergency medicine, geriatric medicine, intensive care, medical oncology, palliative medicine, renal medicine and respiratory medicine on the AMPCo Direct database in those three Australian states. The survey measured medical specialists' level of legal compliance, and reasons for their decisions, concerning the withholding or withdrawal of life-sustaining treatment. Multivariable logistic regression was used to examine predictors of legal compliance. Linear regression was used to examine associations between the decision about life-sustaining treatment and the relevance of factors involved in making these decisions, as well as state differences in these associations. RESULTS: Response rate was 32% (867/2702). A majority of respondents in each state said that they would provide treatment in a hypothetical scenario, despite an advance directive refusing it: 72% in NSW and Queensland; 63% in Victoria. After applying differences in state law, 72% of Queensland doctors answered in accordance with local law, compared with 37% in Victoria and 28% in NSW (p < 0.001). Doctors reported broadly the same decision-making approach despite differences in local law. CONCLUSIONS: Law appears to play a limited role in medical decision-making at the end of life with doctors prioritising patient-related clinical and ethical considerations. Different legal frameworks in the three states examined did not lead to different decisions about providing treatment. More education is needed about law and its role in this area, particularly where law is inconsistent with traditional practice.

The transcriptional co-factor RIP140 regulates mammary gland development by promoting the generation of key mitogenic signals.

Nuclear receptor interacting protein (Nrip1), also known as RIP140, is a co-regulator for nuclear receptors that plays an essential role in ovulation by regulating the expression of the epidermal growth factor-like family of growth factors. Although several studies indicate a role for RIP140 in breast cancer, its role in the development of the mammary gland is unclear. By using RIP140-null and RIP140 transgenic mice, we demonstrate that RIP140 is an essential factor for normal mammary gland development and that it functions by mediating oestrogen signalling. RIP140-null mice exhibit minimal ductal elongation with no side-branching, whereas RIP140-overexpressing mice show increased cell proliferation and ductal branching with age. Tissue recombination experiments demonstrate that RIP140 expression is required in both the mammary epithelial and stromal compartments for ductal elongation during puberty and that loss of RIP140 leads to a catastrophic loss of the mammary epithelium, whereas RIP140 overexpression augments the mammary basal cell population and shifts the progenitor/differentiated cell balance within the luminal cell compartment towards the progenitors. For the first time, we present a genome-wide global view of oestrogen receptor-α (ERα) binding events in the developing mammary gland, which unravels 881 ERα binding sites. Unbiased evaluation of several ERα binding sites for RIP140 co-occupancy reveals selectivity and demonstrates that RIP140 acts as a co-regulator with ERα to regulate directly the expression of amphiregulin (Areg), the progesterone receptor (Pgr) and signal transducer and activator of transcription 5a (Stat5a), factors that influence key mitogenic pathways that regulate normal mammary gland development.

What does "futility" mean? An empirical study of doctors' perceptions.

OBJECTIVE: To investigate how doctors define and use the terms "futility" and "futile treatment" in end-of-life care. DESIGN, SETTING, PARTICIPANTS: A qualitative study using semi-structured interviews with 96 doctors from a range of specialties which treat adults at the end of life. Doctors were recruited from three large Brisbane teaching hospitals and were interviewed between May and July 2013. RESULTS: Doctors' conceptions of futility focused on the quality and prospect of patient benefit. Aspects of benefit included physiological effect, weighing benefits and burdens, and quantity and quality of life. Quality and length of life were linked, but many doctors discussed instances in which benefit was determined by quality of life alone. Most described assessing the prospects of achieving patient benefit as a subjective exercise. Despite a broad conceptual consensus about what futility means, doctors noted variability in how the concept was applied in clinical decision making. More than half the doctors also identified treatment that is futile but nevertheless justified, such as short term treatment that supports the family of a dying person. CONCLUSIONS: There is an overwhelming preference for a qualitative approach to assessing futility, which inevitably involves variability in clinical decision making. Patient benefit is at the heart of doctors' definitions of futility. Determining patient benefit requires discussing with patients and their families their values and goals as well as the burdens and benefits of further treatment.

Palliative care and other physicians' knowledge, attitudes and practice relating to the law on withholding/withdrawing life-sustaining treatment: Survey results.

BACKGROUND: To effectively care for people who are terminally ill, including those without decision-making capacity, palliative care physicians must know and understand the legal standing of Advance Care Planning in their jurisdiction of practice. This includes the use of advance directives/living wills and substitute decision-makers who can legally consent to or refuse treatment if there is no valid advance directive. AIM: This study aimed to investigate the knowledge, attitudes and practices of medical specialists most often involved in end-of-life care in relation to the law on withholding/withdrawing life-sustaining treatment from adults without decision-making capacity. DESIGN/PARTICIPANTS: A pre-piloted survey was posted to specialists in palliative, emergency, geriatric, renal and respiratory medicine; intensive care; and medical oncology in three Australian States. Surveys were analysed using SPSS 20 and SAS 9.3. RESULTS: The overall response rate was 32% (867/2702) - 52% from palliative care specialists. Palliative care specialists and geriatricians had significantly more positive attitudes towards the law (χ42(2) = 94.352; p < 0.001) and higher levels of knowledge about the withholding/withdrawing life-sustaining treatment law (χ7(2) = 30.033; p < 0.001) than did the other specialists, while still having critical gaps in their knowledge. CONCLUSION: A high level of knowledge of the law is essential to ensure that patients' wishes and decisions, expressed through Advance Care Planning, are respected to the maximum extent possible within the law, thereby according with the principles and philosophy of palliative care. It is also essential to protect health professionals from legal action resulting from unauthorised provision or cessation of treatment.

Reasons doctors provide futile treatment at the end of life: a qualitative study.

OBJECTIVE: Futile treatment, which by definition cannot benefit a patient, is undesirable. This research investigated why doctors believe that treatment that they consider to be futile is sometimes provided at the end of a patient's life. DESIGN: Semistructured in-depth interviews. SETTING: Three large tertiary public hospitals in Brisbane, Australia. PARTICIPANTS: 96 doctors from emergency, intensive care, palliative care, oncology, renal medicine, internal medicine, respiratory medicine, surgery, cardiology, geriatric medicine and medical administration departments. Participants were recruited using purposive maximum variation sampling. RESULTS: Doctors attributed the provision of futile treatment to a wide range of inter-related factors. One was the characteristics of treating doctors, including their orientation towards curative treatment, discomfort or inexperience with death and dying, concerns about legal risk and poor communication skills. Second, the attributes of the patient and family, including their requests or demands for further treatment, prognostic uncertainty and lack of information about patient wishes. Third, there were hospital factors including a high degree of specialisation, the availability of routine tests and interventions, and organisational barriers to diverting a patient from a curative to a palliative pathway. Doctors nominated family or patient request and doctors being locked into a curative role as the main reasons for futile care. CONCLUSIONS: Doctors believe that a range of factors contribute to the provision of futile treatment. A combination of strategies is necessary to reduce futile treatment, including better training for doctors who treat patients at the end of life, educating the community about the limits of medicine and the need to plan for death and dying, and structural reform at the hospital level.

Is There a Role for Law in Medical Practice When Withholding and Withdrawing Life-Sustaining Medical Treatment? Empirical Findings on Attitudes of Doctors.

The law regulates many aspects of decision-making around the withholding and withdrawing of life-sustaining medical treatment from adults who lack decision-making capacity and are approaching the end of their lives. For example, it governs whether an adult's advance directive is binding and applicable and, if not, who is authorised to make the treatment decision and the criteria that should guide the decision. Doctors who treat patients at the end of life should be aware of the prevailing law so that they can practise within those legal parameters. However, the law in this field is complex and challenging for doctors to know and understand. Doctors will be prepared to invest time into learning about the law only if they believe that the law is worth knowing and that practising medicine in a legally compliant way is a desirable goal. This article provides insight into doctors' attitudes about the role of law in medical practice in this field, and argues that education is required for doctors to reconceptualise knowledge of the law as constituting an integral component of their clinical expertise.

The Knowledge and Practice of Doctors in Relation to the Law That Governs Withholding and Withdrawing Life-Sustaining Treatment from Adults Who Lack Capacity.

Law establishes a framework for making decisions about withholding and withdrawing life-sustaining treatment from adults who lack capacity. However, to what extent do doctors know and follow this law? This article reports on a three-year empirical study that sought to answer these questions. The research found that doctors have significant legal knowledge gaps in this area. It also found that doctors do not attach significant weight to legal considerations in their decision-making. This article argues that law does have a role to play in end-of-life care. However, law reform is needed to make the law more accessible, medical education needs to be improved, and a change in attitude by doctors to medical law is required.

Genetic coregulation of age of female sexual maturation and lifespan through circulating IGF1 among inbred mouse strains.

We previously reported that mouse strains with lower circulating insulin-like growth factor 1 (IGF1) level at 6 mo have significantly extended longevity. Here we report that strains with lower IGF1 have significantly delayed age of female sexual maturation, measured by vaginal patency (VP). Among strains with normal lifespans (mean lifespan >600 d), delayed age of VP associated with greater longevity (P = 0.015), suggesting a genetically regulated tradeoff at least partly mediated by IGF1. Supporting this hypothesis, C57BL/6J females had 9% lower IGF1, 6% delayed age of VP, and 24% extended lifespan compared with C57BL/6J.C3H/HeJ-Igf1, which carries a C3H/HeJ allele on chromosome (Chr) 10 that increases IGF1. To identify genetic loci/genes that regulate female sexual maturation, including loci that mediate lifespan tradeoffs, we performed haplotype association mapping for age of VP and identified significant loci on Chrs 4 (Vpq1) and 16 (Vpq2 and 3). At each locus, wild-derived strains share a unique haplotype that associates with delayed VP. Substitution of Chr 16 of C57BL/6J with Chr 16 from a wild-derived strain significantly reduced IGF1 and delayed VP. Strains with a wild-derived allele at Vpq3 have significantly extended longevity compared with strains with other alleles. Bioinformatic analysis identified Nrip1 at Vpq3 as a candidate gene. Nrip1(-/-) females have significantly reduced IGF1 and delayed age of VP compared with Nrip1(+/+) females. We conclude that IGF1 may coregulate female sexual maturation and longevity; wild-derived strains carry specific alleles that delay sexual maturation; and Nrip1 is involved in regulating sexual maturation and may affect longevity by regulating IGF1 level.

Clayton's compromises and the assisted dying debate.

Richard Huxtable has recently argued that while assisted dying has been both repeatedly condemned and commended, a compromise resolution is possible. Following critique of other purported solutions, he argues for a new legal offence of "compassionate killing" as a plausible compromise between supporters and opponents of legalised assisted dying, because it offers something of significance to both sides. However, it turns out that "compassionate killing" would leave both sides with insufficient net benefit for the proposal to qualify as a compromise between them. By analogy with another apparently intractable bioethical debate, concerning destructive embryo research, this column rejects Huxtable's solution as another "Clayton's compromise". True compromise is not possible in bioethical debates involving divisions over deeply held values and world views. Resolving such debates inevitably involves the substitution of one dominant world view with another.

"NEVER REGARD YOURSELF AS ALREADY SO THOROUGHLY INFORMED": THE WITHDRAWAL OF ITS INVITATION TO RODNEY SYME TO ADDRESS ITS 2015 CONGRESS BY THE ROYAL AUSTRALASIAN COLLEGE OF PHYSICIANS.

In 1628, William Harvey presented his revolutionary theory of the circulation to ears at the Royal College of Physicians that had been deafened by the unquestionable authority of Galen's teachings, from one and a half millennia in the past. Harvey's theory was initially rejected, despite his faith in his colleagues being eager for truth and knowledge, and never regarding themselves as so well informed that they would not welcome "further information". Recently Rodney Syme, the retired Melbourne urologist who for a long time has agitated for the legalisation of assisted dying, and also challenged the authorities to apply the current law in response to his admitted assistance to a number of individuals, was invited to address the 2015 Congress of the Royal Australasian College of Physicians. At the eleventh hour, the invitation to speak was withdrawn. In this column, we trace the course of events leading to this withdrawal of the invitation, and describe some of the correspondence to and from the College in response to the withdrawal. We draw parallels between the experiences of Harvey and Syme, and point to lessons to be learnt from the recent episode of apparent unwillingness, on the part of an institution that seeks to present itself as outward-looking, progressive and socially aware, to fulfil this promise in the increasingly important area of the end-of-life.