The origin of the genetic code has been attributed in part to an accidental assignment of codons to amino acids. Although several lines of evidence indicate the subsequent expansion and improvement of the genetic code, the hypothesis of Francis Crick concerning a frozen accident occurring at the early stage of genetic code evolution is still widely accepted. Considering Crick’s hypothesis, mathematical descriptions of hypothetical scenarios involving a huge number of possible coexisting random genetic codes could be very important to explain (...) the origin and evolution of a selected genetic code. This work aims to contribute in this regard, that is, it provides a theoretical framework in which statistical parameters of error functions are calculated. Given a genetic code and an amino acid property, the functional code robustness is estimated by means of a known error function. In this work, using analytical calculations, general expressions for the average and standard deviation of the error function distributions of completely random codes with standard stop codons were obtained. As a possible biological application of these results, any set of amino acids and any pure or mixed amino acid properties can be used in the calculations, such that, in case of having to select a set of amino acids to create a genetic code, possible advantages of natural selection of the genetic codes could be discussed. (shrink)

Theoretical minimal RNA rings are candidate primordial genes evolved for non‐redundant coding of the genetic code's 22 coding signals (one codon per biogenic amino acid, a start and a stop codon) over the shortest possible length: 29520 22‐nucleotide‐long RNA rings solve this min‐max constraint. Numerous RNA ring properties are reminiscent of natural genes. Here we present analyses showing that all RNA rings lack dinucleotide CG (a mutable, chemically instable dinucleotide coding for Arginine), bearing a resemblance to known (...) CG‐depleted genomes. CG in “incomplete” RNA rings (not coding for all coding signals, with only 3–12 nucleotides) gradually decreases towards CG absence in complete, 22‐nucleotide‐long RNA rings. Presumably, feedback loops during RNA ring growth during evolution (when amino acid assignment fixed the genetic code) assigned Arg to codons lacking CG (AGR) to avoid CG. Hence, as a chemical property of base pairs, CG mutability restructured the genetic code, thereby establishing itself as genetically encoded biological information. (shrink)

Gene expression is an inherently complex process and errors often occur during the transcription and processing of mRNAs. Several surveillance mechanisms have evolved to check the fidelity at each step of mRNA manufacture. Two recent reports describe the identification of a novel pathway in eukaryotes that recognizes and degrades mRNAs that lack a stop codon.1,2 The non‐stop decay mechanism releases ribosomes stalled at the 3′ end of a mRNA and stimulates the exosome to rapidly degrade the transcript. (...) BioEssays 24:785–788, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

The rational design of theoretical minimal RNA rings predetermines AUG as the universal start codon. This design maximizes coded amino acid diversity over minimal sequence length, defining in silico theoretical minimal RNA rings, candidate ancestral genes. RNA rings code for 21 amino acids and a stop codon after three consecutive translation rounds, and form a degradation‐delaying stem‐loop hairpin. Twenty‐five RNA rings match these constraints, ten start with the universal initiation codon AUG. No first codon bias (...) exists among remaining RNA rings. RNA ring design predetermines AUG as initiation codon. This is the only explanation yet for AUG as start codon. RNA ring design determines additional RNA ring gene‐ and tRNA‐like properties described previously, because it presumably mimics constraints on life's primordial RNAs. (shrink)

The genetic code is a set of instructions that determine how the information in our genetic material is translated into amino acids. In general, it is universal for all organisms, from viruses and bacteria to humans. However, in the last few decades, exceptions to this rule have been identified both in pro‐ and eukaryotes. In this review, we discuss the 16 described alternative eukaryotic nuclear genetic codes and observe theories of their appearance in evolution. We consider possible molecular mechanisms that (...) allow codon reassignment. Most reassignments in nuclear genetic codes are observed for stop codons. Moreover, in several organisms, stop codons can simultaneously encode amino acids and serve as termination signals. In this case, the meaning of the codon is determined by the additional factors besides the triplets. A comprehensive review of various non‐standard coding events in the nuclear genomes provides a new insight into the translation mechanism in eukaryotes. (shrink)

Theoretical minimal RNA rings attempt to mimick life’s primitive RNAs. At most 25 22-nucleotide-long RNA rings code once for each biotic amino acid, a start and a stop codon and form a stem-loop hairpin, resembling consensus tRNAs. We calculated, for each RNA ring’s 22 potential splicing positions, similarities of predicted secondary structures with tRNA vs. rRNA secondary structures. Assuming rRNAs partly derived from tRNA accretions, we predict positive associations between relative secondary structure similarities with rRNAs over tRNAs and (...) genetic code integration orders of RNA ring anticodon cognate amino acids. Analyses consider for each secondary structure all nucleotide triplets as potential anticodon. Anticodons for ancient, chemically inert cognate amino acids are most frequent in the 25 RNA rings. For RNA rings with primordial cognate amino acids according to tRNA-homology-derived anticodons, tRNA-homology and coding sequences coincide, these are separate for predicted cognate amino acids that presumably integrated late the genetic code. RNA ring secondary structure similarity with rRNA over tRNA secondary structures associates best with genetic code integration orders of anticodon cognate amino acids when assuming split anticodons (one and two nucleotides at the spliced RNA ring 5′ and 3′ extremities, respectively), and at predicted anticodon location in the spliced RNA ring’s midst. Results confirm RNA ring homologies with tRNAs and CDs, ancestral status of tRNA half genes split at anticodons, the tRNA-rRNA axis of RNA evolution, and that single theoretical minimal RNA rings potentially produce near-complete proto-tRNA sets. Hence genetic code pre-existence determines 25 short circular gene- and tRNA-like RNAs. Accounting for each potential splicing position, each RNA ring potentially translates most amino acids, realistically mimicks evolution of the tRNA-rRNA translation machinery. These RNA rings ‘of creation’ remind the uroboros’ (snake biting its tail) symbolism for creative regeneration. (shrink)

Mutations that disrupt biological rhythms have existed in microbial and metazoan eukaryotes for some time. They have recently begun to be studied with increasing intensity, both in terms of phenotypic effects of the relevant genetic variants, and with regard to molecular isolation and analysis of the genes defined by two of the ‘clock mutations’. These genetic loci, called period (per) in Drosophila and frequency (frq) in Neurospora, influence not only the basic characteristics of circadian rhythmicity, but also temperature compensation of (...) such daily cycle durations, ‘re‐setting’ of the rhythms' phases, and (for the per mutants) behavioral oscillations associated with much shorter than circadian periodicities. Molecular cloning of Drosophila's per gene, accompanied crucially by the locus's identification in germ‐line transformants, has led to information on its expression ‐ temporally, spatially, and in regard to heterogeneity of mRNA types. Nucleotide‐sequencing analyses of genomic DNA (and/or cDNA) from normal and mutated per alleles have (1) led to the suggestion that this clock gene encodes a family of proteoglycans (which was further indicated by application of antibody reagents obtained by manipulation of one of the gene's exons); and (2) shown that the three types of per mutations ‐ which shorten or lengthen rhythm periodicities or appear to eliminate them ‐ are associated with interesting amino‐acid substitutions or a stop codon, respectively. Analogous molecular findings are awaited from Neurospora, whose frq gene has very recently been cloned and definitively identified, in part via transformation experiments. (shrink)

The α‐actinins are an ancient family of actin‐binding proteins that play structural and regulatory roles in cytoskeletal organisation and muscle contraction. α‐actinin‐3 is the most‐highly specialised of the four mammalian α‐actinins, with its expression restricted largely to fast glycolytic fibres in skeletal muscle. Intriguingly, a significant proportion (∼18%) of the human population is totally deficient in α‐actinin‐3 due to homozygosity for a premature stop codon polymorphism (R577X) in the ACTN3 gene. Recent work in our laboratory has revealed a (...) strong association between R577X genotype and performance in a variety of athletic endeavours. We are currently exploring the function and evolutionary history of the ACTN3 gene and other α‐actinin family members. The α‐actinin family provides a fascinating case study in molecular evolution, illustrating phenomena such as functional redundancy in duplicate genes, the evolution of protein function, and the action of natural selection during recent human evolution. BioEssays 26:786–795, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Mitochondrial genomes represent relict bacterial genomes derived from a progenitor α‐proteobacterium that gave rise to all mitochondria through an ancient endosymbiosis. Evolution has massively reduced these genomes, yet despite relative simplicity their organization and expression has developed considerable novelty throughout eukaryotic evolution. Few organisms have reengineered their mitochondrial genomes as thoroughly as the protist lineage of dinoflagellates. Recent work reveals dinoflagellate mitochondrial genomes as likely the most gene‐impoverished of any free‐living eukaryote, encoding only two to three proteins. The organization and (...) expression of these genomes, however, is far from the simplicity their gene content would suggest. Gene duplication, fragmentation, and scrambling have resulted in an inflated and complex genome organization. Extensive RNA editing then recodes gene transcripts, and trans‐splicing is required to assemble full‐length transcripts for at least one fragmented gene. Even after these processes, messenger RNAs (mRNAs) lack canonical start codons and most transcripts have abandoned stop codons altogether. (shrink)

Translation of the genetic code occurs in a cycle where ribosomes engage mRNAs, synthesize protein, and then disengage in order to repeat the process again. The final part of this process—ribosome recycling, where ribosomes dissociate from mRNAs—involves a complex molecular choreography of specific protein factors to remove the large and small subunits of the ribosome in a coordinated fashion. Errors in this process can lead to the accumulation of ribosomes at stop codons or translation of downstream open reading frames (...) (ORFs). Ribosome recycling is also critical when a ribosome stalls during the elongation phase of translation and must be rescued to allow continued translation of the mRNA. Here we discuss the molecular interactions that drive ribosome recycling, and their regulation in the cell. We also examine the consequences of inefficient recycling with regards to disease, and its functional roles in synthesis of novel peptides, regulation of gene expression, and control of mRNA‐associated proteins. Alterations in ribosome recycling efficiency have the potential to impact many cellular functions but additional work is needed to understand how this regulatory power is utilized. (shrink)

Name der Zeitschrift: Byzantinische Zeitschrift Jahrgang: 111 Heft: 1 Seiten: 157-212.

The canonical genetic code ubiquitously translates nucleotide into peptide sequence with several alterations known in viruses, bacteria, mitochondria, plastids, and single‐celled eukaryotes. A new hypothesis to explain genetic code changes, termed tRNA loss driven codon reassignment, has been proposed recently when the polyphyly of the yeast codon reassignment events has been uncovered. According to this hypothesis, the driving force for genetic code changes are tRNA or translation termination factor loss‐of‐function mutations or loss‐of‐gene events. The free codon can (...) subsequently be captured by all tRNAs that have an appropriately mutated anticodon and are efficiently charged. Thus, codon capture most likely happens by near‐cognate tRNAs and tRNAs whose anticodons are not part of the recognition sites of the respective aminoacyl‐tRNA‐synthetases. This hypothesis comprehensively explains the CTG codon translation as alanine in Pachysolen yeast together with the long known translation of the same codon as serine in Candida albicans and related species, and can also be applied to most other known. (shrink)

Although voluntarily stopping eating and drinking as a way to hasten one’s death is not yet a widely recognized practice in the United States, it has received increasing attention in the medical and bioethics literature in recent years. After a brief review of the broader context of human death and dying, this article poses and examines 11 conceptual, personal, and public policy questions about VSED. The article identifies essential features of VSED and discusses whether VSED is a type of suicide. (...) It identifies reasons why people may or may not choose VSED, and it considers responses by family members and professional caregivers to people who have chosen VSED. It also considers how public policies may permit and regulate or restrict the practice of VSED. Examination of these questions is designed to increase understanding of VSED and to inform moral evaluation of this practice. (shrink)

Since 2016, there has been an explosion of academic work and journalism that fixes its subject matter using the terms ‘fake news’ and ‘post-truth’. In this paper, I argue that this terminology is not up to scratch, and that academics and journalists ought to completely stop using the terms ‘fake news’ and ‘post-truth’. I set out three arguments for abandonment. First, that ‘fake news’ and ‘post-truth’ do not have stable public meanings, entailing that they are either nonsense, context-sensitive, or (...) contested. Secondly, that these terms are unnecessary, because we already have a rich vocabulary for thinking about epistemic dysfunction. Thirdly, I observe that ‘fake news’ and ‘post-truth’ have propagandistic uses, meaning that using them legitimates anti-democratic propaganda, and runs the risk of smuggling bad ideology into conversations. (shrink)

The aim of the paper is to bring out exactly what makes first-personal contents special, by showing that they perform a distinctive cognitive function. Namely, they are stopping points of inquiry. First, I articulate this idea and then I use it to clear the ground from a troublesome conflation. That is, the conflation of this particular function all first-person thoughts have with the property of immunity to error through misidentification, which only some I-thoughts enjoy. Afterward, I show the implications of (...) this idea for a theory of first-person content and of immunity to error though misidentification. I then make some comparisons with Pryor’s notion of wh-misidentification and immunity thereof and with Cappelen and Dever’s position on immunity to error through misidentification and show why they are defective. (shrink)

Research has begun to suggest that cognitive ability contributes to emotional processes and responses. The present study sought novel evidence for this hypothesis by examining the relationship between individual differences in the capacity for inhibitory control and responses to a common emotion-induction procedure involving autobiographical memories. Participants first completed a stop-signal task to measure inhibitory control and then underwent an anger, anxiety, or neutral emotion induction. Performance on the stop-signal task predicted emotional responses such that participants with poorer (...) inhibitory control reported larger increases in anger following the anger induction and larger increases in anxiety across emotion induction conditions, relative to better inhibitors. These results suggest that individual differences in cognitive ability may influence the intensity of emotional states induced by common laboratory methods of emotion induction. (shrink)

Stopping rules — rules dictating when to stop accumulating data and start analyzing it for the purposes of inferring from the experiment — divide Bayesians, Likelihoodists and classical statistical approaches to inference. Although the relationship between Bayesian philosophy of science and stopping rules can be complex (cf. Steel 2003), in general, Bayesians regard stopping rules as irrelevant to what inference should be drawn from the data. This position clashes with classical statistical accounts. For orthodox statistics, stopping rules do matter (...) to what inference should be drawn from the data. "The dispute over stopping rule is far from being a marginal quibble, but is instead a striking illustration of the divergence of fundamental aims and standards separating Bayesians and advocates of orthodox statistical methods" (Steel 2004, 195) ... (shrink)

Error statistics is an important methodological view in philosophy of statistics and philosophy of science that can be applied to scientific experiments such as clinical trials. In this paper, I raise two potential issues for ES when it comes to guiding, and explaining early stopping of randomized controlled trials : ES provides limited guidance in cases of early unfavorable trends due to the possibility of trend reversal; ES is silent on how to prospectively control error rates in experiments requiring multiple (...) interim analyses. The method of conditional power, together with a rationing principle for RCTs, can assist ES in addressing such issues. (shrink)

Refusal of lifesaving treatment, and such refusal by advance directive, are widely recognized as ethically and legally permissible. Voluntarily stopping eating and drinking is not. Ethically and legally, how does VSED compare with these two more established ways for patients to control the end of life? Is it more questionable because with VSED the patient intends to cause her death, or because those who assist it with palliative care could be assisting a suicide?In fact the ethical and legal basis for (...) VSED is virtually as strong as for refusing lifesaving treatment and less problematic than the basis for refusing treatment by advance directive. VSED should take its proper place among the accepted, permissible ways by which people can control the time and manner of death. (shrink)

“Don’t be jealous of your sister.” “Don’t be angry with your father.” “You should be more forgiving.” “You ought to feel terrible for what you’ve done.” “You ought to feel ashamed of yourself!” It is common practice within our society to morally reprimand people for their emotions, thereby expressing a kind of moralism: the idea that there are morally right and morally wrong ways to feel. Drawing on an alternative way of engaging with emotions derived from my experience working clinically (...) with people with personality disorders, I argue against the value of this common practice and the moralization of emotions that underpins it. Stop telling people what to feel! (shrink)

Aversive memories have the potential to impair one’s psychological well-being. It is desirable to reduce the anguish over such memories, as well as the chance that they will be retrieved. In two experiments, we investigated whether retrieval stopping reduces the distress elicited by negative memories retrieved from cues and how the effects of retrieval stopping are modulated by mental disorders, such as depression and anxiety. Participants engaged in retrieval stopping of aversive scene memories without any diversionary thoughts (direct suppression, Experiment (...) 1) or with diversionary positive thoughts (thought substitution, Experiment 2). Direct suppression reduced arousal elicited by the retrieval of aversive memories, while thought substitution did not only reduce arousal but also increased positive valence. Self-reported anxious/depressive symptoms negatively modulated the effects of direct suppression. For no or mild anxious/depressed individuals, direct suppression alleviated negative valence and high arousal when retrieving aversive memories. The negative relationship was not observed between the severity of the symptoms and the effect of thought substitution. These findings suggest that both retrieval stopping strategies can reduce distress from aversive memories. (shrink)

A “stopping rule” in a sequential experiment is a rule or procedure for deciding when that experiment should end. Accordingly, the “stopping rule principle” states that, in a sequential experiment, the evidential relationship between the final data and an hypothesis under consideration does not depend on the experiment’s stopping rule: the same data should yield the same evidence, regardless of which stopping rule was used. In this essay, I reconstruct and rebut five independent arguments for the SRP. Reminding oneself that (...) the stopping rule is a part of an experiment’s design and is no more mysterious than many other design aspects helps elucidate why some of these arguments for the SRP are unsound. (shrink)

In this paper, I present a puzzle about epistemic rationality. It seems plausible that it should be rational to believe a proposition if you have sufficient evidential support for it. It seems plausible that it rationality requires you to conform to the categorical requirements of rationality. It also seems plausible that our first-order attitudes ought to mesh with our higher-order attitudes. It seems unfortunate that we cannot accept all three claims about rationality. I will present three ways of trying to (...) resolve this tension and argue that the best way to do this is to reject the idea that strong evidential support is the stuff rationality is made of. In the course of doing this, I shall argue that there is a special class of propositions about the requirements of rationality that we cannot make rational mistakes about and explain how this can be. (shrink)

We study the performance of heuristics relative to the performance of optimal solutions in the rich domain of sequential search, where the decision to stop the search depends only on the applicant’s relative rank. Considering multiple variants of the secretary problem, that vary from one another in their formulation and method of solution, we find that descriptive heuristics perform well only when the optimal solution prescribes a single threshold value. We show that a computational heuristic originally proposed as an (...) approximate solution to a single variant of the secretary problem performs equally well in many other variants where the optimal solution prescribes multiple threshold values that gradually relax the criterion for stopping the search. Finally, we propose a new heuristic with near optimal performance in a competitive or strategic variant of the secretary problem with multiple employers competing with one another to hire job applicants. Both heuristics share a simple computational component: the ratio of the number of interviewed applicants to the number of those remaining to be searched. We present the subgame-perfect Nash equilibrium for this competitive variant and an algorithm for its computation. (shrink)

The stopping rule for a sequential experiment is the rule or procedure for determining when that experiment should end. Accordingly, the stopping rule principle (SRP) states that the evidential relationship between the final data from a sequential experiment and a hypothesis under consideration does not depend on the stopping rule: the same data should yield the same evidence, regardless of which stopping rule was used. I clarify and provide a novel defense of two interpretations of the main argument against the (...) SRP, the foregone conclusion argument. According to the first, the SRP allows for highly confirmationally unreliable experiments, which concept I make precise, to confirm highly. According to the second, it entails the evidential equivalence of experiments differing significantly in their confirmational reliability. I rebut several attempts to deflate or deflect the foregone conclusion argument, drawing connections with replication in science and the likelihood principle. (shrink)

This book is about the turn toward consciousness by which we pass from ignorance to knowledge. The stop is the spark of initiation that arouses our habitual inattentiveness, motivating us toward a higherunderstanding.

Contrary to W. Murray Hunt’s suggestion, living things deserve moral consideration and inanimate objects do not precisely because living things can intelligibly be said to have interests (and inanimate objects cannot intelligibly said to have interests). Interests are crucial because the concept of morality is noncontingently related to beneficence or nonmaleficence, notions which misfire completely in theabsence of entities capable of being benefited or harmed.

This article explores a distinctive representational strategy used in stop-motion animation: the object substitution. Using as its central example a children’s TV episode in which brushes stand in for dogs, it explains how this strategy produces a complex relationship between depiction and representation. The analysis highlights the pragmatic underpinnings of various theories of pictorial and cinematic representation, arguing that, in a substitution, depicted elements constitute explicatures and represented ones implicatures. Connecting this strategy to humans’ capacity for pareidolia (seeing things (...) in other things), it contends that an object substitution achieves its effects—and reconciles its marked incongruities—by prompting viewers to pleasurably reverse-engineer the far-fetched projective imagining that motivated its use. This process, which is a form of conceptual blending, is based on relations that are neither straightforwardly iconic nor purely arbitrary. (shrink)

This article explores two related widespread mistakes in thinking about sexual harassment. One is a mistake made by philosophers doing philosophical work on the topic of sexual harassment: an excessive focus on attempting to define the term ‘sexual harassment’. This is a perfectly legitimate topic for discussion and indeed a necessary one, but its dominance of the literature has tended to prevent philosophers from adequately exploring other topics that are of at least equal importance, particularly that of bystanders' responsibilities. The (...) other mistake is one made not just by philosophers but by most people attempting to deal with real-world behaviour that is either sexual harassment or closely related to sexual harassment: an excessive focus on whether or not formal charges of sexual harassment are possible or appropriate. (This is clearly related to the first mistake in that a part of deciding whether charges are appropriate is deciding whether the behaviour meets the definition of sexual harassment.) I argue that these are not merely unfortunate errors in attempting to conceptualise certain problematic behaviours; they have extremely damaging real world effects. (shrink)

Some feminist discourses blame some men for gender inequality, gender domination, and gender-based violence. Some women use such discourse as a perfect scenario to criticize some men’s behavior. Indeed, they usually do so with Oppressed Traditional Masculinities but not with Dominant Traditional Masculinities, who are the men who were violent with those women and with whom some of those women chose to have relationships. However, there have always been men who have been on the side of women and have never (...) committed violence against them. Therefore, New Alternative Masculinities reject being indicated as guilty of the violence committed against women by DTM. Through a communicative approach, applying six semi-structured interviews with a communicative orientation and a communicative data analysis of all information, this article explores both women’s communicative acts that blame OTM for what DTM have done to women and NAM’s reactions to these accusations to stop such blaming to make it possible to overcome hegemonic discourses. (shrink)

This book is about the turn toward consciousness by which we pass from ignorance to knowledge. The stop is the spark of initiation that arouses our habitual inattentiveness, motivating us toward a higherunderstanding.

What if you're not who you think you are? What if you don't really know the people closest to you? And what if your most deeply-held beliefs turn out to be. wrong? In Stop Being Reasonable, philosopher Eleanor Gordon-Smith tells gripping true stories that show the limits of human reason. Susie realises her husband harbours a terrible secret, Dylan leaves the cult he's been raised in since birth, Alex discovers he can no longer return to his former identity after (...) impersonating someone else on reality TV. All of them radically alter their beliefs about the things that matter most. What makes them change course? What does this say about our own beliefs? And, in an increasingly divided world, what does it teach us about how we might change the minds of others? Stop Being Reasonable is a mind-changing exploration of the murky place where philosophy and real life meet. (shrink)

The paper analyzes the impact of massive capital flows and possible sudden stops on current account reversals. The aim of this paper is to consider the relationship between sudden stops and current account reversals in the eurozone and to explain the possibility of a balance-of-payment crisis within a monetary union. Peripheral eurozone countries experienced significant private-capital inflows from the core countries, followed by unambiguously massive outflows. Due to this, peripheral countries ran sustained current account deficits while core countries ran surpluses. (...) At the end we analyze the evolution of current-account balances in the non-euro area EU countries and the peripheral euro-area countries, and we find out that current account deficits could be maintained over a longer period of time in the peripheral euro-area countries. (shrink)

This issue’s “Legal Briefing” column covers recent legal developments involving voluntarily stopping eating and drinking (VSED). Over the past decade, clinicians and bioethicists have increasingly recognized VSED as a medically and ethically appropriate means to hasten death. Most recently, in September 2013, the National Hospice and Palliative Care Organization (NHPCO) called on its 2,000 member hospices to develop policies and guidelines addressing VSED. And VSED is getting more attention not only in healthcare communities, but also in the general public. For (...) example, VSED was recently highlighted on the front page of the New York Times and in other national and local media. Nevertheless, despite the growing interest in VSED, there remains little onpoint legal authority and only sparse bioethics literature analyzing its legality. This article aims to fill this gap. Specifically, we focus on new legislative, regulatory, and judicial acts that clarify the permissibility of VSED. We categorize these legal developments into the following seven categories: 1. Definition of VSED2. Uncertainty Whether Oral Nutrition and Hydration Are Medical Treatment3. Uncertainty Regarding Providers’ Obligations to Patients Who Choose VSED4. Judicial Guidance from Australia5. Judicial Guidance from the United Kingdom6. Judicial Guidance from Canada7. Case of Margot Bentley. (shrink)