The Value of Cancer Prevention vs Treatment

We present an integrated valuation model for diseases that pose some chance of death. The model extends the standard one-period value-of-statistical-life model to three health prospects: healthy, ill, and dead. We derive willingness-to-pay values for preven- tion eorts that reduce a disease’s incidence rate as well as for treatments that lower the corresponding health deterioration and mortality rates. We find that the demand value of prevention always exceeds that of treatment. People often overweight small risks and underweight large ones. We use the rank dependent utility framework to explore how the demand for prevention and treatment alters when people evaluate probabilities in a non-linear manner. For incidence and mortality rates associated with common types of cancers, the inverse-S shaped probability weighting found in experimental studies leads to a significant increment in the demand values of both treatment and prevention

Gating the pore of the calcium-activated chloride channel TMEM16A

The binding of cytoplasmic Ca2+ to the anion-selective channel TMEM16A triggers a conformational change around its binding site that is coupled to the release of a gate at the constricted neck of an hourglass-shaped pore. By combining mutagenesis, electrophysiology, and cryo-electron microscopy, we identified three hydrophobic residues at the intracellular entrance of the neck as constituents of this gate. Mutation of each of these residues increases the potency of Ca2+ and results in pronounced basal activity. The structure of an activating mutant shows a conformational change of an α-helix that contributes to Ca2+ binding as a likely cause for the basal activity. Although not in physical contact, the three residues are functionally coupled to collectively contribute to the stabilization of the gate in the closed conformation of the pore, thus explaining the low open probability of the channel in the absence of Ca2+

Time of Arrival from Bohmian Flow

We develop a new conception for the quantum mechanical arrival time distribution from the perspective of Bohmian mechanics. A detection probability for detectors sensitive to quite arbitrary spacetime domains is formulated. Basic positivity and monotonicity properties are established. We show that our detection probability improves and generalises earlier proposals by Leavens and McKinnon. The difference between the two notions is illustrated through application to a free wave packet.Comment: 18 pages, 8 figures, to appear in Journ. Phys. A; representation of ref. 5 improved (thanks to Rick Leavens

Features of 80S mammalian ribosome and its subunits

It is generally believed that basic features of ribosomal functions are universally valid, but a systematic test still stands out for higher eukaryotic 80S ribosomes. Here we report: (i) differences in tRNA and mRNA binding capabilities of eukaryotic and bacterial ribosomes and their subunits. Eukaryotic 40S subunits bind mRNA exclusively in the presence of cognate tRNA, whereas bacterial 30S do bind mRNA already in the absence of tRNA. 80S ribosomes bind mRNA efficiently in the absence of tRNA. In contrast, bacterial 70S interact with mRNA more productively in the presence rather than in the absence of tRNA. (ii) States of initiation (Pi), pre-translocation (PRE) and post-translocation (POST) of the ribosome were checked and no significant functional differences to the prokaryotic counterpart were observed including the reciprocal linkage between A and E sites. (iii) Eukaryotic ribosomes bind tetracycline with an affinity 15 times lower than that of bacterial ribosomes (Kd 30 μM and 1–2 μM, respectively). The drug does not effect enzymatic A-site occupation of 80S ribosomes in contrast to non-enzymatic tRNA binding to the A-site. Both observations explain the relative resistance of eukaryotic ribosomes to this antibiotic

A Qualitative Analysis of Motivators to Participation in Suicide-Focused Research from a Community-Based Australian Sample

Suicide prevention strategies internationally appear to be falling short of making a meaningful impact on global suicide deaths. Increasing the rates of general community participation in suicide research may improve knowledge generalisability as it relates to suicidal behaviour and leads to new suicide prevention approaches. This study aims to explore the motivations of a community-based sample to participate in suicide research. A subsample of the Australian general population took part in an online survey which is part of a multilevel suicide prevention trial. The survey concluded with an optional open-text question asking about peoples’ motivations for participating in the study; 532 participants left a response to this question. These responses were qualitatively analysed using Thematic Network Analysis. Motivations to participate in suicide research were represented by four global themes: altruism, solve systemic problems, lived experience, and personal benefit. Of these themes, three were focused on the benefit of others, while only the final theme articulated motivation to participate that was self-focused. The impact of suicide is felt throughout the wider community. This new understanding of the motivations of community-based samples to participate in suicide research should be used to increase participation rates and reach people who would not normally contribute their voice to suicide researc

Bohmian trajectories and Klein's paradox

We compute the Bohmian trajectories of the incoming scattering plane waves for Klein's potential step in explicit form. For finite norm incoming scattering solutions we derive their asymptotic space-time localization and we compute some Bohmian trajectories numerically. The paradox, which appears in the traditional treatments of the problem based on the outgoing scattering asymptotics, is absent.Comment: 14 pages, 3 figures; minor format change

Valuing non-marginal changes in mortality and morbidity risk

Many stated-preference studies that seek to estimate the marginal willingness-to-pay (WTP) for reductions in mortality or morbidity risk su˙er from inadequate scope sensitivity. One possible reason is that the risk reductions presented to respondents are too small to be meaningful. Survey responses may thus not accurately reflect respondents’ preferences for health and safety. In this paper we propose a novel approach to estimating the value per statistical life (VSL) or the value per statistical case (VSC) based on larger risk reductions measurable as percentages. While such non-marginal risk reductions are easier to understand, they introduce well known biases. We propose a methodology to de-bias VSL and VSC estimates derived from the evaluation of non-marginal risk reductions and present a proof of concept using simulated stated preference data