The ethics of digital well-being: a multidisciplinary perspective

This chapter serves as an introduction to the edited collection of the same name, which includes chapters that explore digital well-being from a range of disciplinary perspectives, including philosophy, psychology, economics, health care, and education. The purpose of this introductory chapter is to provide a short primer on the different disciplinary approaches to the study of well-being. To supplement this primer, we also invited key experts from several disciplines—philosophy, psychology, public policy, and health care—to share their thoughts on what they believe are the most important open questions and ethical issues for the multi-disciplinary study of digital well-being. We also introduce and discuss several themes that we believe will be fundamental to the ongoing study of digital well-being: digital gratitude, automated interventions, and sustainable co-well-being

Immune-mediated competition in rodent malaria is most likely caused by induced changes in innate immune clearance of merozoites

Malarial infections are often genetically diverse, leading to competitive interactions between parasites. A quantitative understanding of the competition between strains is essential to understand a wide range of issues, including the evolution of virulence and drug resistance. In this study, we use dynamical-model based Bayesian inference to investigate the cause of competitive suppression of an avirulent clone of Plasmodium chabaudi (AS) by a virulent clone (AJ) in immuno-deficient and competent mice. We test whether competitive suppression is caused by clone-specific differences in one or more of the following processes: adaptive immune clearance of merozoites and parasitised red blood cells (RBCs), background loss of merozoites and parasitised RBCs, RBC age preference, RBC infection rate, burst size, and within-RBC interference. These processes were parameterised in dynamical mathematical models and fitted to experimental data. We found that just one parameter μ, the ratio of background loss rate of merozoites to invasion rate of mature RBCs, needed to be clone-specific to predict the data. Interestingly, μ was found to be the same for both clones in single-clone infections, but different between the clones in mixed infections. The size of this difference was largest in immuno-competent mice and smallest in immuno-deficient mice. This explains why competitive suppression was alleviated in immuno-deficient mice. We found that competitive suppression acts early in infection, even before the day of peak parasitaemia. These results lead us to argue that the innate immune response clearing merozoites is the most likely, but not necessarily the only, mediator of competitive interactions between virulent and avirulent clones. Moreover, in mixed infections we predict there to be an interaction between the clones and the innate immune response which induces changes in the strength of its clearance of merozoites. What this interaction is unknown, but future refinement of the model, challenged with other datasets, may lead to its discovery

The stellar halo of the Galaxy

Stellar halos may hold some of the best preserved fossils of the formation history of galaxies. They are a natural product of the merging processes that probably take place during the assembly of a galaxy, and hence may well be the most ubiquitous component of galaxies, independently of their Hubble type. This review focuses on our current understanding of the spatial structure, the kinematics and chemistry of halo stars in the Milky Way. In recent years, we have experienced a change in paradigm thanks to the discovery of large amounts of substructure, especially in the outer halo. I discuss the implications of the currently available observational constraints and fold them into several possible formation scenarios. Unraveling the formation of the Galactic halo will be possible in the near future through a combination of large wide field photometric and spectroscopic surveys, and especially in the era of Gaia.Comment: 46 pages, 16 figures. References updated and some minor changes. Full-resolution version available at http://www.astro.rug.nl/~ahelmi/stellar-halo-review.pd

Very high energy particle acceleration powered by the jets of the microquasar SS 433

SS 433 is a binary system containing a supergiant star that is overflowing its Roche lobe with matter accreting onto a compact object (either a black hole or neutron star). Two jets of ionized matter with a bulk velocity of $\sim0.26c$ extend from the binary, perpendicular to the line of sight, and terminate inside W50, a supernova remnant that is being distorted by the jets. SS 433 differs from other microquasars in that the accretion is believed to be super-Eddington, and the luminosity of the system is $\sim10^{40}$ erg s$^{-1}$. The lobes of W50 in which the jets terminate, about 40 pc from the central source, are expected to accelerate charged particles, and indeed radio and X-ray emission consistent with electron synchrotron emission in a magnetic field have been observed. At higher energies (>100 GeV), the particle fluxes of $\gamma$ rays from X-ray hotspots around SS 433 have been reported as flux upper limits. In this energy regime, it has been unclear whether the emission is dominated by electrons that are interacting with photons from the cosmic microwave background through inverse-Compton scattering or by protons interacting with the ambient gas. Here we report TeV $\gamma$-ray observations of the SS 433/W50 system where the lobes are spatially resolved. The TeV emission is localized to structures in the lobes, far from the center of the system where the jets are formed. We have measured photon energies of at least 25 TeV, and these are certainly not Doppler boosted, because of the viewing geometry. We conclude that the emission from radio to TeV energies is consistent with a single population of electrons with energies extending to at least hundreds of TeV in a magnetic field of $\sim16$~micro-Gauss.Comment: Preprint version of Nature paper. Contacts: S. BenZvi, B. Dingus, K. Fang, C.D. Rho , H. Zhang, H. Zho

Identification and functional characterisation of CRK12:CYC9, a novel cyclin-dependent kinase (CDK)-cyclin complex in Trypanosoma brucei

The protozoan parasite, Trypanosoma brucei, is spread by the tsetse fly and causes trypanosomiasis in humans and animals. Both the life cycle and cell cycle of the parasite are complex. Trypanosomes have eleven cdc2-related kinases (CRKs) and ten cyclins, an unusually large number for a single celled organism. To date, relatively little is known about the function of many of the CRKs and cyclins, and only CRK3 has previously been shown to be cyclin-dependent in vivo. Here we report the identification of a previously uncharacterised CRK:cyclin complex between CRK12 and the putative transcriptional cyclin, CYC9. CRK12:CYC9 interact to form an active protein kinase complex in procyclic and bloodstream T. brucei. Both CRK12 and CYC9 are essential for the proliferation of bloodstream trypanosomes in vitro, and we show that CRK12 is also essential for survival of T. brucei in a mouse model, providing genetic validation of CRK12:CYC9 as a novel drug target for trypanosomiasis. Further, functional characterisation of CRK12 and CYC9 using RNA interference reveals roles for these proteins in endocytosis and cytokinesis, respectively

A Scoping Review of Home Produced Heroin and Amphetamine Type Stimulant Substitutes: Implications for Prevention, Treatment and Policy

Several home-produced substances such as krokodil and boltushka are prevalent in many Eastern European countries. Anecdotal reports of its use have been circulating in Germany and Norway; however, this has not been confirmed. Its use has also been reported by the media in the USA, although only one confirmed report of its use exists. Home-produced drugs are associated with high levels of morbidity and a number of complex health issues such as the spread of blood borne viruses, gangrene, and internal organ damage. The high incidence of HIV rates amongst people who inject home-produced substances is a public health concern. The resulting physical health consequences of injecting these crude substances are very severe in comparison to heroin or amphetamine acquired in black markets. Due to this fact and the increased mortality associated with these substances, professionals in the area of prevention, treatment, and policy development need to be cognisant of the presentation, harms, and the dangers associated with home-produced substances globally. This scoping review aimed to examine existing literature on the subject of home-produced heroin and amphetamine-type stimulant substitutes. The review discussed the many implications such research may have in the areas of policy and practice. Data were gathered through the use of qualitative secondary resources such as journal articles, reports, reviews, case studies, and media reports. The home production of these substances relies on the utilisation of precursor drugs such as less potent stimulants, tranquillizers, analgesics, and sedatives or natural plant ingredients. The Internet underpins the facilitation of this practice as recipes, and diverted pharmaceutical sales are available widely online, and currently, ease of access to the Internet is evident worldwide. This review highlights the necessity of prevention, education, and also harm reduction related to home-produced drugs and also recommends consistent monitoring of online drug fora, online drug marketplaces, and unregulated pharmacies

NPR3 and NPR4 are receptors for the immune signal salicylic acid in plants

Salicylic acid (SA) is a plant immune signal produced upon pathogen challenge to induce systemic acquired resistance (SAR). It is the only major plant hormone for which the receptor has not been firmly identified. SAR in Arabidopsis requires the transcription cofactor NPR1 (nonexpresser of PR genes 1), whose degradation serves as a molecular switch for SAR. Here we show that NPR1 paralogues, NPR3 and NPR4, are SA receptors that bind SA with different affinities and function as adaptors of the Cullin 3 ubiquitin E3 ligase to mediate NPR1 degradation in an SA-regulated manner. Accordingly, the npr3 npr4 mutant accumulates higher levels of NPR1 and is insensitive to SAR induction. Moreover, this mutant is defective in pathogen effector-triggered programmed cell death and immunity. Our study reveals the mechanism of SA perception in determining cell death and survival in response to pathogen challenge

A Neptune-sized transiting planet closely orbiting a 5–10-million-year-old star

Theories of the formation and early evolution of planetary systems postulate that planets are born in circumstellar disks, and undergo radial migration during and after dissipation of the dust and gas disk from which they formed^1, 2. The precise ages of meteorites indicate that planetesimals—the building blocks of planets—are produced within the first million years of a star’s life^3. Fully formed planets are frequently detected on short orbital periods around mature stars. Some theories suggest that the in situ formation of planets close to their host stars is unlikely and that the existence of such planets is therefore evidence of large-scale migration^4, 5. Other theories posit that planet assembly at small orbital separations may be common^6, 7, 8. Here we report a newly born, transiting planet orbiting its star with a period of 5.4 days. The planet is 50 per cent larger than Neptune, and its mass is less than 3.6 times that of Jupiter (at 99.7 per cent confidence), with a true mass likely to be similar to that of Neptune. The star is 5–10 million years old and has a tenuous dust disk extending outward from about twice the Earth–Sun separation, in addition to the fully formed planet located at less than one-twentieth of the Earth–Sun separation

Predicting the Electron Requirement for Carbon Fixation in Seas and Oceans

Marine phytoplankton account for about 50% of all global net primary productivity (NPP). Active fluorometry, mainly Fast Repetition Rate fluorometry (FRRf), has been advocated as means of providing high resolution estimates of NPP. However, not measuring CO2-fixation directly, FRRf instead provides photosynthetic quantum efficiency estimates from which electron transfer rates (ETR) and ultimately CO2-fixation rates can be derived. Consequently, conversions of ETRs to CO2-fixation requires knowledge of the electron requirement for carbon fixation (Φe,C, ETR/CO2 uptake rate) and its dependence on environmental gradients. Such knowledge is critical for large scale implementation of active fluorescence to better characterise CO2-uptake. Here we examine the variability of experimentally determined Φe,C values in relation to key environmental variables with the aim of developing new working algorithms for the calculation of Φe,C from environmental variables. Coincident FRRf and 14C-uptake and environmental data from 14 studies covering 12 marine regions were analysed via a meta-analytical, non-parametric, multivariate approach. Combining all studies, Φe,C varied between 1.15 and 54.2 mol e- (mol C)-1 with a mean of 10.9±6.91 mol e- mol C)-1. Although variability of Φe,C was related to environmental gradients at global scales, region-specific analyses provided far improved predictive capability. However, use of regional Φe,C algorithms requires objective means of defining regions of interest, which remains challenging. Considering individual studies and specific small-scale regions, temperature, nutrient and light availability were correlated with Φe,C albeit to varying degrees and depending on the study/region and the composition of the extant phytoplankton community. At the level of large biogeographic regions and distinct water masses, Φe,C was related to nutrient availability, chlorophyll, as well as temperature and/or salinity in most regions, while light availability was also important in Baltic Sea and shelf waters. The novel Φe,C algorithms provide a major step forward for widespread fluorometry-based NPP estimates and highlight the need for further studying the natural variability of Φe,C to verify and develop algorithms with improved accuracy. © 2013 Lawrenz et al

Common genetic variants near the Brittle Cornea Syndrome locus ZNF469 influence the blinding disease risk factor central corneal thickness Publication

Copyright: © 2010 Lu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Central corneal thickness (CCT), one of the most highly heritable human traits (h2 typically>0.9), is important for the diagnosis of glaucoma and a potential risk factor for glaucoma susceptibility. We conducted genome-wide association studies in five cohorts from Australia and the United Kingdom (total N = 5058). Three cohorts were based on individually genotyped twin collections, with the remaining two cohorts genotyped on pooled samples from singletons with extreme trait values. The pooled sample findings were validated by individual genotyping the pooled samples together with additional samples also within extreme quantiles. We describe methods for efficient combined analysis of the results from these different study designs. We have identified and replicated quantitative trait loci on chromosomes 13 and 16 for association with CCT. The locus on chromosome 13 (nearest gene FOXO1) had an overall meta-analysis p-value for all the individually genotyped samples of 4.6×10−10. The locus on chromosome 16 was associated with CCT with p = 8.95×10−11. The nearest gene to the associated chromosome 16 SNPs was ZNF469, a locus recently implicated in Brittle Cornea Syndrome (BCS), a very rare disorder characterized by abnormal thin corneas. Our findings suggest that in addition to rare variants in ZNF469 underlying CCT variation in BCS patients, more common variants near this gene may contribute to CCT variation in the general population