Palliative care, double effect and the law in Australia

Care and decision-making at the end of life that promotes comfort and dignity is widely endorsed by public policy and the law. In ethical analysis of palliative care interventions that are argued potentially to hasten death, these may be deemed to be ethically permissible by the application of the doctrine of double effect, if the doctor’s intention is to relieve pain and not cause death. In part because of the significance of ethics in the development of law in the medical sphere, this doctrine is also likely to be recognized as part of Australia’s common law, although hitherto there have been no cases concerning palliative care brought before a court in Australia to test this. Three Australian States have, nonetheless, created legislative defences that are different from the common law with the intent of clarifying the law, promoting palliative care, and distinguishing it from euthanasia. However, these defences have the potential to provide less protection for doctors administering palliative care. In addition to requiring a doctor to have an appropriate intent, the defences insist on adherence to particular medical practice standards and perhaps require patient consent. Doctors providing end-of-life care in these States need to be aware of these legislative changes. Acting in accordance with the common law doctrine of double effect may not provide legal protection. Similar changes are likely to occur in other States and Territories as there is a trend towards enacting legislative defences that deal with the provision of palliative care

Antigenic evolution of SARS-CoV-2 in immunocompromised hosts

Prolonged infections of immunocompromised individuals have been proposed as a crucial source of new variants of SARS-CoV-2 during the COVID-19 pandemic. In principle, sustained within-host antigenic evolution in immunocompromised hosts could allow novel immune escape variants to emerge more rapidly, but little is known about how and when immunocompromised hosts play a critical role in pathogen evolution. Here, we use a simple mathematical model to understand the effects of immunocompromised hosts on the emergence of immune escape variants in the presence and absence of epistasis. We show that when the pathogen does not have to cross a fitness valley for immune escape to occur (no epistasis), immunocompromised individuals have no qualitative effect on antigenic evolution (although they may accelerate immune escape if within-host evolutionary dynamics are faster in immunocompromised individuals). But if a fitness valley exists between immune escape variants at the between-host level (epistasis), then persistent infections of immunocompromised individuals allow mutations to accumulate, therefore facilitating rather than simply speeding up antigenic evolution. Our results suggest that better genomic surveillance of infected immunocompromised individuals and better global health equality, including improving access to vaccines and treatments for individuals who are immunocompromised (especially in lower- and middle-income countries), may be crucial to preventing the emergence of future immune escape variants of SARS-CoV-2

Multi-mode fluctuating selection in host-parasite coevolution

Understanding fluctuating selection is important for our understanding of patterns of spatial and temporal diversity in nature. Host-parasite theory has classically assumed fluctuations either occur between highly specific genotypes (Matching Alleles: MA) or from specialism to generalism (Gene-for-Gene: GFG). However, while MA can only generate one mode of fluctuating selection, we show that GFG can in fact produce both rapid “within-range” fluctuations (among genotypes with identical levels of investment but which specialise on different subsets of the population) and slower cycling “between ranges” (different levels of investment), emphasising that MA is a subset of GFG. Our findings closely match empirical observations, although sampling rates need to be high to detect these novel dynamics empirically. Within-range cycling is an overlooked process by which fluctuating selection can occur in nature, suggesting that fluctuating selection may be a more common and important process than previously thought in generating and maintaining diversity

Herd immunity

Herd immunity is an important yet often misunderstood concept in epidemiology. As immunity accumulates in a population — naturally during the course of an epidemic or through vaccination — the spread of an infectious disease is limited by the depletion of susceptible hosts. If a sufficient proportion of the population is immune — above the ‘herd immunity threshold’ — then transmission generally cannot be sustained. Maintaining herd immunity is therefore critical to long-term disease control. In this primer, we discuss the concept of herd immunity from first principles, clarify common misconceptions, and consider the implications for disease control. Much is being said about herd immunity these days. But the concept, though seemingly simple, is often misunderstood. Ben Ashby and Alex Best explain what exactly herd immunity is, how it is achieved in a population, how it is lost, and what it means for disease control.</p

Duality based error control for the Signorini problem

In this paper we study the a posteriori bounds for a conforming piecewise linear finite element approximation of the Signorini problem. We prove new rigorous a posteriori estimates of residual type in $L^{p}$, for $p \in (4,\infty)$ in two spatial dimensions. This new analysis treats the positive and negative parts of the discretisation error separately, requiring a novel sign- and bound-preserving interpolant, which is shown to have optimal approximation properties. The estimates rely on the sharp dual stability results on the problem in $W^{2,(4 - \varepsilon)/3}$ for any $\varepsilon \ll 1$. We summarise extensive numerical experiments aimed at testing the robustness of the estimator to validate the theory

Population mixing promotes arms race host-parasite coevolution.

Open access article. Please cite the published version available on the Royal Society web site by following the DOI above.The consequences of host-parasite coevolution are highly contingent on the qualitative coevolutionary dynamics: whether selection fluctuates (fluctuating selection dynamic; FSD), or is directional towards increasing infectivity/resistance (arms race dynamic; ARD). Both genetics and ecology can play an important role in determining whether coevolution follows FSD or ARD, but the ecological conditions under which FSD shifts to ARD, and vice versa, are not well understood. The degree of population mixing is thought to increase host exposure to parasites, hence selecting for greater resistance and infectivity ranges, and we hypothesize this promotes ARD. We tested this by coevolving bacteria and viruses in soil microcosms and found that population mixing shifted bacteria-virus coevolution from FSD to ARD. A simple theoretical model produced qualitatively similar results, showing that mechanisms that increase host exposure to parasites tend to push dynamics towards ARD. The shift from FSD to ARD with increased population mixing may help to explain variation in coevolutionary dynamics between different host-parasite systems, and more specifically the observed discrepancies between laboratory and field bacteria-virus coevolutionary studies.Natural Environment Research Council (NERC)Marie Curie Intra-European Fellowship (FP7)The Royal Societ