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In their recent paper1, Maples et al. surveyed users of the Replika app2. Among their results, they reported that participants were relatively lonely and used Replika for diverse purposes, and emphasized that "3% reported that Replika halted their suicidal ideation"1. However, important context about how Replika has been marketed and used was missing. We provide context about Replika's sexual component, and discuss the threat of industry interests to scientific integrity.

Covid-19 forced higher education sectors across the world to digitize the entire university experience online. There are now calls for universities to continue chasing continued and further digitization, often from for-profit businesses and those in Silicon Valley who have been promising to disrupt the sector for decades. We argue that the pandemic has illustrated how crucial universities are to their local communities, and efforts should be made to emphasize their physical place and space. The destruction of American cities in favor of auto-centric suburbs provides a parallel for the possible future of higher education. The Cult of Efficiency mindset and accountability models that dominated neoliberal discourse offered the impetus for highway construction through city centers, often razing Black neighborhoods and ruining communities and culture along the way. The calls for the full digitization of universities echo this same possible destruction for the sector. This is not a Luddite warning to reject all digitization, instead, it is a rejection of the hyper-capitalization of higher education and the disruption promised by for-profit businesses, along with a reminder that the sector should be a local public good.

My professional lifetime has seen progress in the biomedical sciences that beggars belief. This has lead to astonishing advances in the ability to prevent and treat disease and, in the developed world at least, people live longer and healthier lives than ever before. Paradoxically, this has gone hand in hand with the growth of a vocal and influential anti-science lobby that not only rejects much modern science but is also deeply suspicious of new medical interventions. The prospect of cell therapy in the near or middle future is their current target especially where the use of embryonic stem cells or of cell nuclear transfer techniques is concerned. The prospect of cell therapy is welcomed with enthusiasm by patients with genetic and degenerative diseases who hope to benefit from them. On the other hand the whole idea is regarded as repugnant by the anti-science lobby. While some of this opposition is essentially luddite in nature, there are some more persuasive arguments raised particularly to any research than uses embryonic or foetal materials. These arguments will be examined critically. The moral problems of denying the sick the hope of effective treatments have to be weighed against those seen in the development of such treatments. (This article is closely based on an already published paper. P. Lachmann, Stem cell research: why is it regarded as a threat? An investigation of the economic and ethical arguments made against research with human embryonic stem cells.

United States health care is engaged in an ambitious project to make its clinical and administrative records "100% electronic." Substantial benefits are expected in both clinical care delivery and medical research (especially for public health surveillance and outcomes/effectiveness studies). Substantial costs also potentially accrue, beyond the large outlays for an expanded computer and telecommunications infrastructure. Privacy and confidentiality are obviously at risk if such systems cannot be made secure. Limited empirical evidence currently available suggests health information systems security may not be very good, at least in the "average" institutional setting. Privacy-focused critics of electronic record-keeping are sometimes accused of taking Luddite stands, insufficiently attentive to IT's benefits. It may also be fair to worry about a certain Panglossian tendency in "industry" commentary, insufficiently attentive to potential problems. Better federal and state laws structuring health data use will help; the industry must also attend more candidly to the technical uncertainties.

I offer an interpretation of hackers' technological choices through a theoretical framework of critique and recuperation in technological cycles, building on prior research that brings the pragmatic sociology of Boltanski and Chiapello to bear on matters in Science and Technology Studies. I argue that contextualizing technology choices in the development of capitalism through innovation illuminates their political significance. I start with the counterintuitive observation that some browser extensions popular with hackers, like RequestPolicy, make it considerably harder for them to look at websites. This observation showcases the Luddite aspects of hackerdom, in that they are willing to 'break' popular websites that would otherwise cheat on the user. In line with an undercurrent of hacker studies, in this case study I find hackers fighting technological progress they see as social decline.

A dietary source of retinoid or carotenoid has been shown to be necessary for the biosynthesis of functional visual pigment in flies. In the present study, the larvae or adults of Drosophila melanogaster were administered specific carotenoid-containing diets and high performance liquid chromatography was used to identify and quantify the carotenoids in extracts of wild type and ninaD visual mutant flies. When beta-carotene was fed to larvae, wild type flies were shown to hydroxylate this molecule and to accumulate zeaxanthin and a small amount of beta-cryptoxanthin. Zeaxanthin content was found to increase throughout development and was a major carotenoid peak detected in the adult fly. Carotenoids were twice as effective at mediating zeaxanthin accumulation when provided to larvae versus adults. In the ninaD mutant, zeaxanthin content was shown to be specifically and significantly altered compared to wild type, and was ineffective at mediating visual pigment synthesis when provided to both larval and adult mutant flies. It is proposed that zeaxanthin is the larval storage form for subsequent visual pigment chromophore biosynthesis during pupation, that zeaxanthin or beta-crytoxanthin is the immediate precursor for light-independent chromophore synthesis in the adult, and that the ninaD mutant is defective in this pathway.

Diagnostic metagenomics and its associated trail of publications are spreading across the world. Multiple clinical labs in the United States, Europe, and Asia have gone to considerable lengths to optimize and validate a range of protocols for agnostically detecting viral, bacterial, fungal, and eukaryotic parasite nucleic acid across a range of patient specimens to aid in diagnosis for particularly recalcitrant cases. Others see a role for diagnostic metagenomics as a frontline diagnostic to replace other microbiological testing. Areas covered: There are considerable barriers to adoption for diagnostic metagenomics, including analytical sensitivity, interpretation, actionability, turnaround time, antimicrobial susceptibility, clinical utility, laboratory workflow, trial comparators, cost, and reimbursement. Expert commentary: Metagenomics is unlikely to become 'one test to rule them all' any time soon, not least because it is not indicative of historical infection like some of the highest volume tests in the clinical virology lab, viral serologies. The high cost and low marginal utility compared to 'standard of care' diagnostics have forced metagenomics to be mostly used for last-ditch cases. However, waiting for such patients to declare themselves as being diagnostically challenging in turn likely lessens the diagnostic yield and actionability of the information. Significant reductions in the cost of metagenomic sequencing are required for it to move up in the diagnostic pipeline. This review covers these associated obstacles of metagenomics, arguing for a parsimonious role in last-ditch diagnostics and awaiting the answer of many outstanding questions regarding its adoption.

1. Time-resolved cell membrane capacitance (Cm) measurements were used in combination with fura-2 microfluorometry under whole-cell patch clamp recording to investigate the kinetics and Ca2+ sensitivity of exocytotic granule fusion evoked by depolarizing stimuli at single, isolated nerve endings of the rat neurohypophysis. 2. Single step depolarizations or trains of depolarizing pulses evoked voltage-dependent, inward Ca2+ currents (ICa) and induced both Ca(2+)-dependent and Ca(2+)-independent changes in Cm. Three distinct Cm responses were observed and were differentiated by their kinetics and Ca2+ sensitivity: a non-exocytotic transient (delta Cm,t) and an exocytotic Cm 'jump' (delta Cm,J) and a slower, often latent, exocytotic Cm rise (delta Cm,s) that outlasted the depolarizing pulse stimulus. 3. The delta Cm,t was characterized by a rapid, transient component observed in 70% of nerve endings and a voltage-activation relationship that preceded that of the ICa. The amplitude and kinetics of the delta Cm,t were unaffected by ICa block by Cd2+, Ca2+ load reduction, or alterations in intracellular Ca2+ buffering. 4. In contrast to the delta Cm,t, both the delta Cm,J and delta Cm,s were Ca2+ dependent as evidenced by their sensitivity to Cd2+ block of ICa, intraterminal application of 10 mM BAPTA and reduced [Ca2+]o or replacement of Ca2+ as the charge carrier with Ba2+. 5. The delta Cm,J was proportional to depolarization-evoked Ca2+ influx with initial exocytotic rate of approximately 350 granule fusions s-1. The amplitude of the delta Cm,J rose exponentially (tau = 40 ms) and approached an asymptote (15.5 fF) with longer duration depolarizations indicating the fusion from and depletion of an immediately releasable pool (IRP) estimated at nineteen docked and primed secretory granules. 6. The delta Cm,s was induced by the application of repetitive long duration pulses and defined as the exocytosis of secretory granules from a readily releasable granule pool (RRP). The delta Cm,s response occurred only after exceeding a [Ca2+]i threshold value and rose thereafter in proportion to Ca2+ influx with a mean initial secretory rate of 36 granule fusions s-1. The mean latency for delta Cm,s activation was 850 ms following the initiation of the step depolarizations. The delta Cm,s response magnitude, reflecting the size of the RRP, was dependent on the resting [Ca2+]i and the nerve ending size, and was depletable using repetitive depolarizations of long duration. 7. Recruitment into and release from the RRP and IRP were differentially sensitive to changes in intraterminal Ca2+ buffering conditions. For example, introduction of 5 mM EGTA was shown to have no effect on the evoked IRP but significantly reduced the RRP. In comparison, diminishment of the endogenous Ca2+ buffering capacity of nerve endings by treatment with the mitochondrial Ca2+ uniporter blocker Ruthenium Red (10 microM) potentiated the RRP size but had no significant effect on the IRP size. 8. The present study indicates that the Ca(2+)-dependent recruitment of and release from functionally distinct pools of peptide-containing secretory granules in combination with the [Ca2+]i regulatory properties of neurohypophysial nerve endings may explain both the depletion of peptide release under prolonged stimulus and the potentiation of peptide release observed to occur during recurrent phasic action potential activity in this system.