Complete nucleotide sequences of bovine alpha S2- and beta-casein cDNAs: comparisons with related sequences in other species

The nucleotide sequences corresponding to bovine alpha S2- and beta- casein mRNAs have been determined by cDNA analysis. Both sequences appear to be complete at their 5' ends. The nucleotide sequence of alpha S2-casein, when compared with the corresponding cavine A sequence, helps to define the boundaries of a large amino acid repeat (approximately 80 residues) whereas comparisons with the nucleotide sequences of rat gamma- and mouse epsilon-casein mRNAs also reveal extensive sequence similarities. An alignment of these four sequences shows that the divergence of their translated regions has been characterized by the duplication and deletion of discrete segments of sequence that probably correspond to exons. A high degree of nucleotide substitution is also found when the four sequences are compared, except for well-conserved leader-peptide and phosphorylation-site sequences and, to a lesser extent, the 5'-untranslated regions. Similar comparison of the bovine and rat beta-caseins shows that their divergence has involved a high rate of nucleotide substitution but that no major insertions or deletions of sequence have occurred. The several splice sites that have veen defined in the rat beta-casein gene are likely to have been conserved in the bovine. The contrasting evolutionary histories of the alpha- and beta-casein coding sequences correlate with the distinctive functions of these proteins in the casein micelle system in milk.      

Treatment limitation decisions under uncertainty: the value of subsequent euthanasia

This paper examines how decisions to limit treatment to critically ill patients under uncertainty can be made rationally. Expected utility theory offers one way of making rational decisions under uncertainty. One problem with using this approach is that we may not know the value of each option. One rational course open is to treat until further information becomes available. However, treatment can limit the range of options open. With treatment, a patient may recover such that he no longer requires life-supporting treatment. However, his life may be not worth living. If active euthanasia of %on-terminal'conditions is prohibited, the option of dying will no longer be available. Taking a rational'wait and see'course may result in being trapped within an unbearable life. On the other hand, sometimes present practice'lets nature takes its course'. Critically ill patients are allowed to die because it is believed that their lives will be not worth living. It is likely that some patients are allowed to die when there is some objective chance of worthwhile future life. This paper argues that a policy of treating critically ill patients until the nature of future options can be better evaluated, in company with an offer of subsequent euthanasia where appropriate, allows a more rational and humane approach to treatment limitation decisions under uncertainty.     

Quarantine,isolation and the duty of easy rescue in public health

We address the issue of whether, why and under what conditions, quarantine and isolation are morally justified, with a particular focus on measures implemented in the developing world. We argue that the benefits of quarantine and isolation justify some level of coercion or compulsion by the state, but that the state should be able to provide the strongest justification possible for implementing such measures. While a constrained form of consequentialism might provide a justification for such public health interventions, we argue that a stronger justification is provided by a principle of State Enforced Easy Rescue: a state may permissibly compel individuals to engage in activities that entail a small cost to them but a large benefit to others, because individuals have a moral duty of easy rescue to engage in those activities. The principle of State Enforced Easy Rescue gives rise to an Obligation Enforcement Requirement: the state should create the conditions such that submitting to coercive or compulsive measures becomes a fundamental moral duty of individuals, i.e. a duty of easy rescue. When the state can create such conditions, it has the strongest justification possible for implementing coercive or compulsive measures, because individuals have a moral duty to temporarily relinquish the rights that such measures would infringe. Our argument has significant implications for how public health emergencies in the developing world should be tackled. Where isolation and quarantine measures are necessary, states or the international community have a moral obligation to provide certain benefits to those quarantined or isolated.     

Zika,contraception and the non‐identity problem

The 2016 outbreak of the Zika arbovirus was associated with large numbers of cases of the newly‐recognised Congenital Zika Syndrome (CZS). This novel teratogenic epidemic raises significant ethical and practical issues. Many of these arise from strategies used to avoid cases of CZS, with contraception in particular being one proposed strategy that is atypical in epidemic control. Using contraception to reduce the burden of CZS has an ethical complication: interventions that impact the timing of conception alter which people will exist in the future. This so‐called ‘non‐identity problem’ potentially has significant social justice implications for evaluating contraception, that may affect our prioritisation of interventions to tackle Zika. This paper combines ethical analysis of the non‐identity problem with empirical data from a novel survey about the general public's moral intuitions. The ethical analysis examines different perspectives on the non‐identity problem, and their implications for using contraception in response to Zika. The empirical section reports the results of an online survey of 93 members of the US general public exploring their intuitions about the non‐identity problem in the context of the Zika epidemic. Respondents indicated a general preference for a person‐affecting intervention (mosquito control) over an impersonal intervention (contraception). However, their responses did not appear to be strongly influenced by the non‐identity problem. Despite its potential philosophical significance, we conclude from both theoretical considerations and analysis of the attitudes of the community that the non‐identity problem should not affect how we prioritise contraception relative to other interventions to avoid CZS.     

I-MOVE multi-centre case control study 2010-11: overall and stratified estimates of influenza vaccine effectiveness in Europe

Background

In the third season of I-MOVE (Influenza Monitoring Vaccine Effectiveness in Europe), we undertook a multicentre case-control study based on sentinel practitioner surveillance networks in eight European Union (EU) member states to estimate 2010/11 influenza vaccine effectiveness (VE) against medically-attended influenza-like illness (ILI) laboratory-confirmed as influenza.

Methods

Using systematic sampling, practitioners swabbed ILI/ARI patients within seven days of symptom onset. We compared influenza-positive to influenza laboratory-negative patients among those meeting the EU ILI case definition. A valid vaccination corresponded to > 14 days between receiving a dose of vaccine and symptom onset. We used multiple imputation with chained equations to estimate missing values. Using logistic regression with study as fixed effect we calculated influenza VE adjusting for potential confounders. We estimated influenza VE overall, by influenza type, age group and among the target group for vaccination.

Results

We included 2019 cases and 2391 controls in the analysis. Adjusted VE was 52% (95% CI 30-67) overall (N = 4410), 55% (95% CI 29-72) against A(H1N1) and 50% (95% CI 14-71) against influenza B. Adjusted VE against all influenza subtypes was 66% (95% CI 15-86), 41% (95% CI -3-66) and 60% (95% CI 17-81) among those aged 0-14, 15-59 and ≥60 respectively. Among target groups for vaccination (N = 1004), VE was 56% (95% CI 34-71) overall, 59% (95% CI 32-75) against A(H1N1) and 63% (95% CI 31-81) against influenza B.

Conclusions

Results suggest moderate protection from 2010-11 trivalent influenza vaccines against medically-attended ILI laboratory-confirmed as influenza across Europe. Adjusted and stratified influenza VE estimates are possible with the large sample size of this multi-centre case-control. I-MOVE shows how a network can provide precise summary VE measures across Europe.     

Adaptive evolution of G-protein coupled receptor genes

The phylogeny and patterns of nucleotide substitutions in the visual pigment genes, adrenergic receptor genes, muscarinic receptor genes, and in the human mas oncogene were studied by comparing their DNA sequences. The evolutionary tree obtained shows that the visual pigment genes and mas oncogene form one cluster and that the receptor genes form another. In the evolution of rhodopsin genes, synonymous substitutions outnumber nonsynonymous substitutions. This is consistent with the neutral theory of molecular evolution. However, the early evolutionary stages of alpha- and beta-adrenergic and muscarinic receptors are notable for significantly more nonsynonymous substitutions than synonymous substitutions, suggesting the acquisition of novel functional adaptations. Variable rates of nonsynonymous changes in different domains of these proteins reveal DNA segments that might have been important in their functional adaptations.      

Rational desires and the limitation of life-sustaining treatment

It is accepted that treatment of previously competent, now incompetent patients can be limited if that is what the patient would desire, if she were now competent. Expressed past preferences or an advance directive are often taken to constitute sufficient evidence of what a patient would now desire. I distinguish between desires and rational desires. I argue that for a desire to be an expression of a person's autonomy, it must be or satisfy that person's rational desires. A person rationally desires a course of action if that person desires it while being in possession of all available relevant facts, without committing relevant error of logic, and "vividly imagining" what its consequences would be like for her. I argue that some competent, expressed desires obstruct autonomy. I show that several psychological mechanisms operate to prevent a person rationally evaluating what future life in a disabled state would be like. Rational evaluation is difficult. However, treatment limitation, if it is to respect autonomy, must be in accord with a patient's rational desires, and not merely her expressed desires. I illustrate the implications of these arguments for the use of advance directives and for the treatment of competent patients.