This study explored how Covid-19 lockdown restrictions affected people’s daily smoking routines and behaviours, including adherence and modifications to pre-established smoking restrictions in the home. Semi-structured telephone interviews were conducted with smokers and non-smokers from smoking households 19 to 27 weeks after the first full UK lockdown ended in May 2020. A non-probability purposive sample representing 25 adults aged 21 or over living in households with at least 1 smoker were recruited to the study. A quota sampling strategy was used, according to age, gender, smoking status, family status, household composition, householder access to outdoor space, and change to work-life status. Most participants found lockdown increased the amount of time spent at home, where stresses associated with confinement, curtailment of social routines, removal of barriers and distractions to smoking due to home working, and feelings of boredom all contributed to increased smoking. Fewer factors were identified as reducing smoking during lockdown. Prominent examples included disruption to habitual smoking patterns and distraction from smoking associated with spending more time doing outdoor activities. Pressures placed on physical space and lack of privacy due to the confinement at home were responsible for displacement of smoking within the home, leading to breaking of smoke-free rules and family tensions, and in some cases to greater awareness amongst parents that their children smoked. Changes in daily routines associated with lockdown affected and displaced smoking behaviour both positively and negatively. Health improvement interventions could seek to harness positive changes in smoking associated with any future lockdown approaches. New home-working norms highlight the need for employers to support staff to reduce their smoking and to remain smoke-free. Many governments worldwide responded to the Covid-19 pandemic by introducing lockdowns restricting social contact to limit the transmission of the disease and reduce the risk of health services being overwhelmed. Lockdowns were accompanied by Government communications, encouraging the public to stay at home except for essential purposes. It is important to examine the public health impacts of attempting to contain the spread of Covid-19, as well as the impacts of Covid-19 more generally, as lockdown has been described as a public health intervention in its own right [From the early stages of the pandemic, evidence suggested that smoking is associated with increased severity of disease and death in hospitalised Covid-19 patients ,3. EvideChanges in smoking behaviours may result from pandemic-related changes to the structure of everyday lives ,10. WhilThe UK Government announced the first lockdown in the UK on 23 March 2020, imposed through public health legislation, with separate regulations made in the UK, Scottish and Welsh Parliaments and the Northern Ireland Assembly. England, Scotland, and Wales introduced lockdown restrictions from 26 March to 9 May 2020, and Northern Ireland from 28 March to 17 May 2020, with only minor differences in their respective approaches. The key public health message at this time was to stay at home with limited exceptions including basic food shopping, exercise once per day, medical need and travelling for work when absolutely necessary. Almost all businesses, facilities, places of worship and schools were closed during this time; schooling continued only for children of key workers and children considered vulnerable. One in eight households (12%) in Great Britain had no access to a private or shared garden, patio, or balcony during lockdown, rising to more than one in five in London (21%). Lockdown also highlighted inequalities in access to outdoor space. People of all ethnic minorities are less likely to have outdoor space at home than those of white ethnicity, and people in semi-skilled/unskilled manual occupations are almost three times as likely as those in managerial, administrative and professional occupations to be without a garden (21% v 7%) . PreviouA non-probability purposive sample was generated from an independent UK-wide market research panel, comprised of members of the public who consented to be contacted to participate in online research surveys and telephone interviews. All panel members aged 21 or over  were invited by email to take part in the study and complete a screening questionnaire. Based on screening questionnaire responses, to avoid factors that might confound the impact of lockdown on time-activity patterns at home, those who had (a) moved home between January 2020 and the start of lockdown, (b) been admitted to hospital with COVID-19, or (c) a household member admitted to hospital with COVID-19 were excluded from taking part. Those who opted not to confirm their age, and those who had taken part in three or more studies as part of the independent market research panel in the last six months were also excluded from participating. On this basis, 572 responders were identified as eligible to participate. Thirty-two participants were recruited in order of response to meet a quota sampling strategy based on seven sample variables: gender, age, smoking status, family status, household composition, household access to private outdoor space, and pandemic-related change to work-life status (see 2.5) from SHS and other sources during the UK lockdown to reduce community transmission of Covid-19. Interview questions were developed by DE and RO in discussions with the wider team, and included a focus on changes in household smoking activity, changes in tobacco consumption, frequency of indoor smoking, and changes to daily routines associated with lockdown restrictions, including those related to the amount of time spent indoors at home alone and in the presence of smokers. This provided a detailed picture of how people spent their time before, during, and after full lockdown, and whether and how their smoking behaviour, and the smoking behaviour of others in the household, was affected by disruptions associated with lockdown. The interviews also explored ways in which lockdown restrictions affected household composition and social interactions between household members, including the impact of smoking on family dynamics and adherence and modifications to smoking restrictions in the home. Interview questions were reviewed by DE and RO after the first five interviews were conducted, with no adjustments required.Semi-structured telephone interviews were conducted with adults living in smoking households across the UK between September and November 2020, 19 to 27 weeks after the first full lockdown. The interviews (conducted by DE and RO) used a schedule devised for the wider study, which sought to model the health consequences of changes in personal exposure to fine particulate air pollution .Analysis was led by DE and supported by RO. A core set of themes based on the interview schedule were identified and refined by DE and RO and formed a framework for coding the transcripts (by DE) using NVivo 12 software. The transcripts underwent two stages of analysis. Firstly, they were organised using the thematic framework and potential themes were identified through a process of familiarisation with transcript texts. Then, the transcripts and coded data were re-read and analysed by DE and RO to build a series of individual narratives and case histories. At regular points during the process of data analysis, DE and RO met with members of the wider research team (MS and SS) to discuss identified codes and categories, the interpretation of data and potential new areas of enquiry. The analysis process therefore drew on the combined insights of the researchers most closely involved in data collection and analysis, with wider team perspectives and expertise associated with the topic area.These analyses were also discussed regularly within the wider team, allowing the researchers to identify patterns and differences across the data as a whole and to develop separate participant behaviour profiles.The study was reported in accordance with the 32-item checklist of Consolidated Criteria for Reporting Qualitative Research (COREQ) .Twenty-five adults aged twenty-one and over  took part in the study. Two prospective participants were uncontactable at the time of the scheduled interview. The sample included a broad spectrum of income levels as well as comparable numbers by gender (twelve women and thirteen men), household smoking status . Nine participants were non-smokers and sixteen smoked; four lived alone, nine lived in all-adult households and twelve lived in households with school age/younger children. Fourteen participants lived in homes with access to private outdoor space such as a garden, yard, or balcony, and eleven did not. Sixteen participants lived in homes with smoke-free rules, and nine lived in homes where smoking was permitted (in at least one room).Lockdown affected participants’ working lives in a number of ways. Fifteen participants continued in employment during lockdown: two carried on working with little change; seven were required to work from home; and six were furloughed. One participant who was self-employed ceased working during lockdown unsupported, and two participants were unemployed, one of whom lost his job during full lockdown. Of the remaining seven participants, six were retired, and one was a full-time carer for his wife.Lockdown had a significant impact on the amount of time spent at home and on levels of smoking. On average, the estimated amount of time spent at home across a 24-h day increased by 5.5 h (range −2.3–+11.3 h), with only one participant recording a decrease (P08), attributed to spending more time outdoors. Approximately three-quarters (n = 17) of participants described a change in their smoking levels during/following full lockdown: for most reporting a change, smoking increased (n = 11), with three of these participants reporting a subsequent attempt to reduce intake. Just under a quarter (n = 6) of participants reported reduced smoking during lockdown. In one case this reduction had not been maintained by the time of interviews. Some reductions in smoking were associated with the use of e-cigarettes as a substitute or partial replacement for tobacco.From participants’ accounts of how the changes brought about by lockdown affected their own/other householders’ smoking behaviour, four common themes were generated: changes in routine and boredom; confinement and stress; smoking concealment; and diversionary activity. These four themes reflected both potential influencers on smoking behaviour and ways in which smoking behaviour changed. Illustrative verbatim quotes for each theme are provided alongside participant gender, age, smoking status and work-life status, and household composition  and household access to private outdoor space. All data have been anonymised to protect participant identities.Changes to work and social routines due to lockdown were perceived to have an impact on smoking behaviours. Being furloughed, having a curtailed social life, and finding it difficult to establish new routines led to feelings of listlessness and boredom, which in some cases were contributory factors to increased smoking:My smoking increased twofold… It was boredom more than anything, playing a game or watching TV, and then obviously it would go on a break or it would finish, so then I’d go for a fag.”“So, you said you smoked more during lockdown?”Interviewer: “Yeah, no sauna, no steam, no arranging for tennis, no meeting up with my friends, all those things.” Respondent: “However, for some habitual smokers, furlough helped to break work-related patterns that had previously helped to facilitate smoking habits:He (husband) was definitely smoking less. He said that himself on a couple of occasions… because at work he’s sort of…he’s in and out of jobs so when he’s been on his way to one job he has a cigarette and then he goes in, comes out, has a cigarette on his way to the next job. Whereas at home he’s not doing that.” “For those trying to quit smoking, the disruption to social life caused by lockdown removed important triggers for smoking relapse, including drinking socially:I tried (giving up smoking) before but I’ve never really stuck at it. If I went out drinking, I’d always start back up. And then obviously…how it is at the minute with social distancing, we couldn’t go out together for a fag at work with friends. So yeah, there have been some benefits to lockdown.” “Working from home was also associated with increased smoking, and in some cases with the displacement of smoking into homes. These changes in smoking behaviours were attributed to the removal of features of the workplace that had previously prevented or distracted participants from smoking, including regulated breaks, smoke-free workplace rules, social interaction with work colleagues and more varied work patterns and tasks:I was smoking a lot more during lockdown, because I can, because at work they don’t like it if you go out every ten minutes, it’s a bit rude. So at work I would, you know, I’d start work at eight, and I’d go out sort of twice in the morning and then once in the afternoon, whereas at home I could be lighting up a cigarette every ten minutes.” “The disruption caused by lockdown led some participants to find new ways of socialising, such as meeting with friends remotely or outdoors. These adaptions were also described as providing new opportunities to smoke and, in some cases, facilitated increased smoking:We were doing Zoom calls, because you couldn’t go anywhere,… so there’d be like six or seven of us in our own houses drinking and Zooming….)and) because I was in my house, I would smoke a lot more. Whereas if we were in the pub then I’d have to keep going out for a cigarette…. also the pubs used to shut at 12, whereas we’d be Zooming ‘til two, three and four in the morning.” “There was also some evidence that lockdown and the threat of Covid-19 infection affected tobacco purchasing routines and choices. For example, one smoker’s decision to switch to e-cigarettes was, in part, guided by a wish to limit regular local shopping trips for tobacco to minimise non-essential contact:during lockdown)… It was basically to try and save going to the shop every day (for cigarettes) to minimise contact with people. I didn’t want to have to go to a shop all the time.I was vaping full-time Loss of freedom and the stress of being confined for long hours at home were described as contributing to increased smoking, particularly amongst those living with children and with limited access to outdoor space:Interviewer: “So you found it more stressful during lockdown, is that right?”Respondent: “Yes, (I was probably smoking more…) because you’re cooped up, aren’t you? Basically, in the house rather than having flexibility and a bit of freedom to go out and go to places.” For some parents, confinement proved particularly challenging, with pressures of home schooling and exposure to criticism from children regarding their smoking adding to stress levels. The difficulties of living in a flat with a young family also affected intentions to quit during lockdown and precipitated increased smoking for some:At first I saw it as an opportunity to cut down, but then I think as the situation progressed and having the kids at home I felt more stressed which in turn made me want to smoke more.…They were asking for help with their school work and I’d tell them to hold on a minute—‘Oh, you’re always in the kitchen smoking’, I’d get comments like that from them.” “In other cases, the pressures of looking after children at home with limited access to outdoor space were compounded by additional work-related stresses, which led not only to increased smoking, but also to relaxation of smoking restrictions in the home:He (partner) smoked more because it became very stressful at work….It was the fact none of his  become agitated), so obviously it all adds upclients could go out, so he was having to do more for them in the home. Obviously, they would get cranky and stuff because they weren’t going out, doing their usual activities, so he was coming home, moaning… obviously about how stressed he was, and then my daughter would go off on one really enjoyable’, providing an opportunity for her and her husband to ‘slow down’ and spend more time together with their young family . These positive experiences were associated with a reduction in smoking following disruption of her husband’s work-related smoking patterns.However, not all families found lockdown stressful. For example, one mother described furlough as ‘Lockdown was also associated with efforts to conceal smoking from family members. This was more evident in the accounts of those with limited access to outdoor space, where non-adherence to existing smoke-free home rules and attempts to conceal smoking indoors from other householders could lead to conflict and increased family tensions:He (husband) would go to the bathroom and open the window and then I’d go crazy because of the smell (of smoke)… make excuses for being in there).He tries to close the door and fob me off .Concealment behaviours were also occasionally described by smokers who had access to private outdoor spaces. For example, one recalled moving from one part of the garden to another more private part in order to avoid disapproval from non-smoking members of his household:I was just a bit more conscious that the family were around, you know (wife and daughter both non-smokers). So, if we were doing things outside, I’d be tending to not smoke as much in their presence. Well they’re avid anti-smokers. So I’m a scourge…They’re constantly bickering, ‘cause of the (my) diabetes more than anything else.” “These pressures on living in shared home spaces were sometimes exacerbated when other family members came to live in the household during lockdown, for example sons and daughters returning from university, who were critical of their parents smoking, or where individuals avoided smoking in outdoor public spaces, due to perceived stigma and social unacceptability:I would never be one of those people that would go outside and walk down the street with a cigarette, I’m not one of those people. If I leave the house, I don’t smoke… I wouldn’t smoke in public.” “Children also emerged as a common theme in concealment narratives, for example, parents who sought to hide their smoking from their younger children found this more difficult during lockdown. In one case, a mother who assumed the role of full-time parent during lockdown was unable to smoke in the family flat during the day when her partner was at work. An unintended, positive consequence of these constraints on her freedom to smoke was that it led to her reduced smoking consumption:She wouldn’t (smoke in the flat)…. She’d wait until I got home from work…. Even if she really needed a cigarette, she’d have to wait till I got home…. she’s never smoked up here (in the flat). The kids don’t even know she smokes… she’s always hid it from them.” “Parents also reported lockdown having a significant impact on their teenage children who smoked, with under-age smokers finding it more difficult to conceal their smoking (and e-cigarette use) from parents. In one case, parents described how lockdown had been instrumental in revealing their teenage sons’ smoking habit and the heightened challenges of addressing this at this time:Pre-lockdown we didn’t think he (teenage son) went anywhere near tobacco, but since lockdown he’s...well, I’d say he’s partially addicted to nicotine. He tries to hide it…. I mean, he’s got a cough, which is horrendous, which we keep telling him is due to his smoking. But as I said, he’s suffering with some  issues at the moment, so it’s difficult to get him to understand things at the moment…It’s been massively difficult.” “These and other parents described how lockdown made it more difficult for their teenage children who smoke to obtain tobacco, and how the relative ease with which they could purchase vaping devices and oils meant e–cigarettes were used by under-age smokers as a temporary substitute for tobacco when confined at home:He (teenage son) couldn’t get access to anything and anyone (to obtain cigarettes during full lockdown)…. He was ordering, you know, liquid stuff for vapes (online), but as soon as that went and he was able to see friends, then the pattern changed, basically (he went back to smoking)…I mean, it is illegal for him to smoke, he’s only 15… The vape stuff, they don’t really control very well on websites, but, obviously, tobacco, they do more so.” “Some participants identified outdoor activity and gardening in particular as a means of ‘keeping busy’ during lockdown. Such activities were associated with reductions in smoking, with good weather conditions and longer daylight hours contributing to these changes:I think probably during the hot weather, I didn’t smoke as much. I would keep myself occupied doing other things. Like, when I was gardening, I wouldn’t be smoking because I was too busy. So the more…I suppose the busier I was, the less I smoked.” “Similarly, undertaking internal home improvement projects during lockdown could result in significant reductions in indoor smoking, as householders were keen to instigate new smoke-free rules at home following redecoration. These changes were also facilitated by warm weather conditions reported during the lockdown period, which made smoking outside or by an entrance door easier:Before lockdown I would smoke indoors. But during lockdown, I had to make myself a bit busy, as you do, and I said to my wife, ‘right, let’s decorate the house’. And I hadn’t realised how much the smoke affected the colour of the walls… and that was it, I turned round and said, ‘That’s it, to save me keep painting like this, I’m smoking outside or by the front door’… so it was completely zero (smoking) indoors after I’d decorated.” “These displacement effects resulted in reduced smoking in some cases, particularly when newly decorated areas where smoking was no longer permitted were spaces people had previously used to relax and enjoy a cigarette:Now we’ve got to actually get up (from our seat) and go into the kitchen and spend, say, five minutes away from what you’re doing so you think, ‘I’ll wait ‘til the end of this’ or whatever (before I go through to the kitchen for a smoke)….And also, as well, we’ve got a habit of only having half (a cigarette) and then coming back and having the other half a bit later on. Whereas that wouldn’t happen if we were sitting (relaxing having a smoke) in the front room.” “This study provided novel insights regarding the impacts of changed routines associated with lockdown restrictions on household smoking behaviours. Findings suggest several factors associated with spending more time at home—loss of routine, confinement, and stress, smoking concealment, and diversionary activities—were associated with changes in smoking behaviour. In many cases, working from home was associated with increased smoking and the potential displacement of smoking to indoor home spaces.Our findings support previous studies suggesting that the Covid-19 pandemic has been associated with bidirectional changes in smoking: it has prompted some smokers to increase and others to decrease their smoking ,5,6,7,8.Our findings compliment those of recent research conducted in the UK and Italy ,10, suggRecent research has suggested that the pandemic and lockdown may have provided a ‘teachable moment’ that has prompted changes in health behaviours, including smoking . We did maintenance phase of the Comprehensive Messaging Strategy for Sustained Behaviour Change (CMSSBC) [Our study found that reductions in smoking and reduced smoking in the home were often relatively passive insofar as they were an unplanned consequence of the disruption to usual daily routines brought about by lockdown. Reducing smoking before quitting may appeal to populations who find it particularly difficult to quit smoking, however studies in these populations are limited . Further(CMSSBC) , which iOur findings suggest that in some cases, home working was associated with increases in smoking and the displacement of smoking to indoor spaces. This finding raises concerns regarding increased SHS exposure for non-smoking family members, including children. Whilst homeworking was on a gradual, but slow, upward trajectory in the UK even before the pandemic, it rose considerably during the first lockdown, from 5.7% of workers in January/February 2020 to 43.1% in April 2020 . The newIn the UK, employers must by law prevent people from smoking at work if within an enclosed or substantially enclosed space. Considerable progress has been made in the UK and elsewhere in reducing the proportion of adult smokers who smoke in the home, including through the introduction of smoke-free public places legislation and SHS media campaigns, which have changed social norms related to SHS exposure and increased understanding of the health hazards to non-smokers and children of exposure to SHS ,31,32. WOur findings highlight the potential ways in which disruption to routines during lockdown have impacted on smoking consumption and home smoking behaviours. Whilst the qualitative approach utilised means our findings are not generalisable, the use of quota sampling methods does ensure multiple perspectives and experiences of lockdown are represented. Conducting telephone interviews at the time of the first full lockdown would have enabled exploration of the impacts of lockdown on smoking behaviours ‘in the moment’, which may be more accurate than retrospective accounts. However, our study was able to develop short case histories to illustrate how smoking behaviour evolved over time, from the beginning of the first full lockdown until the time of the interview, which incorporated the shift to partial lockdown (10 May to 4 July 2020). Whilst social desirability may have led to some under-reporting of increased smoking/smoking in the home , previous research suggests that the anonymity of telephone interviews (compared with face-to-face methods) may better equip participants to respond honestly and openly to potentially sensitive questions during qualitative interviews . HoweverWhilst changes in levels of smoking during lockdown were bidirectional, many reported changes related to increased smoking were often explained by a shift to working from home. Similar divergence was also observed in changes to smoking at home, with home improvement projects responsible for householders implementing new restrictions on smoking at home and home working responsible for the relaxation/breaking of rules prohibiting smoking indoors. The emergence of new home working norms highlights the need for employers to support staff to maintain smoke-free workplaces during transitions from work-to-home spaces.


Molecular mechanistic biology has ushered us into the world of life’s building blocks, revealing their interactions in macromolecular complexes and inspiring strategies for detailed functional interrogations. The biogenesis of membraneless cellular compartments, functional mesoscale subcellular locales devoid of strong internal order and delimiting membranes, is among mechanistic biology’s most demanding current challenges. A developing paradigm, biomolecular phase separation, emphasizes solvation of the building blocks through low‐affinity, weakly adhesive unspecific interactions as the driver of biogenesis of membraneless compartments. Here, I discuss the molecular underpinnings of the phase separation paradigm and demonstrate that validating its assumptions is much more challenging than hitherto appreciated. I also discuss that highly specific interactions, rather than unspecific ones, appear to be the main driver of biogenesis of subcellular compartments, while phase separation may be harnessed locally in selected instances to generate material properties tailored for specific functions, as exemplified by nucleocytoplasmic transport. This commentary contrasts the contributions of site‐specific versus unspecific biomolecular interactions to the molecular mechanisms of subcellular compartment assembly and function. CPCchromosomal passenger complexCsatsaturating concentrationFRAPfluorescence recovery after photobleachingIDPintrinsically disordered proteinIDRintrinsically disordered regionsDKdissociation constantkoffdissociation rate constantMVPmultivalent proteinNoLSnucleolar localization signalNORnucleolar organizer regionNPCnuclear pore complexNTRnuclear transport receptorNupsnucleoporinsPRMproline‐rich motifPSphase separationRNPribonucleoproteinSACspindle assembly checkpointSSIsite‐specific interactionmembraneless). Examples that have been known for many decades, among a number of others, are the centrosome, the nucleolus, and P‐granules , has promoted a radically different explanation for how membraneless compartments assemble. Under the PS paradigm, classical specific macromolecular interactions are attributed a secondary role in compartment assembly. Compartments are rather proposed to form under the action of one or a few specific PS drivers . Drawing concepts from polymer chemistry , while other macromolecules attracted to the same compartments through heterotypic interactions  were identified as clients  liquid like and that they arise from liquid–liquid (LL) demixing, a process exemplified by the spontaneous, thermodynamically driven separation of oil from water caused by poor solvation  are homotypic or heterotypic interactions established (mainly) by IDPs, i.e., by proteins, or segments thereof, that do not adopt a stable folded conformation. IDPs are usually viewed as arrays of stickers and spacers, with spacers determining overall solubility, and stickers mediating interactions  are also homotypic or heterotypic, but are enabled by the specific three‐dimensional arrangement (reflecting conformation) and the detailed chemical identity of the binding interfaces. These interactions involve at least one folded domain of a macromolecule and either (type II) a short linear segment of a target macromolecule, which may also fold locally in the process of binding, or (type III) another folded domain. While type I interactions are mediated by a limited set of attractive or repulsive bonds, with the result that their specificity is limited, macromolecular interactions of types II and III usually involve large, conserved surface patches on the interacting macromolecules that exploit the spatial and chemical complementarity of the binding interfaces as well as steric exclusion  to refer to interactions of types II and III.The PS idea identifies interactions of type I typically as et al, D) , correspondingly low concentrations of binders, normally well below their solubility limit, will suffice. SSIs can be easily and rapidly modulated, e.g., through post‐translational modifications, without having to change the concentration of binders. KDs can be extremely low, to the point of making an interaction essentially irreversible, as in the core of many multisubunit macromolecular complexes, or relatively high for regulated interactions, and easily adjustable to non‐equilibrium conditions in active processes. Thus, while in principle, both type I and type II/III interactions can reach high affinity , the hallmark that distinguishes I from II and III is the low specificity of the first and the high specificity of the latter two.SSIs are enormously versatile, as masterly described in a classic review . This allowed PS, initially invoked for the assembly of nuclear and cytoplasmic bodies involved in ribonucleoprotein (RNP) assembly and metabolism, such as nucleoli and P‐granules, to claim for itself an ever‐growing list of cellular territories. PS is now considered a self‐evident universal driver of compartment assembly, as implied by the proposal to rename all membraneless compartments biomolecular condensates , and many more  of any of the interacting components, i.e., in the one‐phase regime. These concerns, to the extent that they call into question the very arguments on which the PS concept has built its success, are highly significant and require thorough motivation. In this essay, I will therefore examine two crucial questions: (i) Are low‐specificity, fuzzy interactions of macromolecules as associative polymers literally the primary physicochemical driver of biogenesis of membraneless compartments in cells under physiological conditions ? and (ii) Can phase transitions influence a compartment’s solvation and material properties after macromolecules have become concentrated there by more traditional binding mechanisms ? Below I will first discuss arguments indicating that the answer to question 1 is (most) likely no. Later, I will also discuss why the answer to question 2 is instead likely yes, but probably for a relatively small subset of compartments. I will also clarify why demonstrating special PS, let alone general PS (if it exists in our cells), requires standards of proof that studies on PS have almost invariably ignored.Another question raised by the definition of above their Csat, a density transition that results in the formation of coexisting dilute and dense phases, each with a fixed concentration of the scaffold , separated by flexible linker spacers  their enrichment in various membraneless compartments and (ii) their tendency, especially for the IDP class, to be aggregation prone and implicated in various degenerative pathologies  , i.e., by the rate of release of the bleached molecules from their receptor, necessary for replacement with new fluorescent molecules  of approximately 100 nM and a t1/2 of recovery in FRAP experiments of ~10 s  complex BUB1/BUB3 binds its kinetochore receptor with a dissociation constant .With the characterization of compartment X in progress, SSIs might have or have not been found. If they had not been found, compartment X might qualify for general PS. If they had been found, there would be a prospect for special PS but also for no PS at all. Thus, if SSIs have been found, the next question is whether they are necessary  for compartment assembly ient Fig . In a stCollectively, the pipeline described above is Part 1 of the test. With compartments being usually very complex, identifying interactions and assessing assembly hierarchies is an extremely demanding task requiring great biochemical prowess and a lot of patience, yielding modest short‐term rewards; but nonetheless essential to real progress.Csat (implying there should be a recognizable Csat). To test PS, we cannot manipulate the SSIs we might have identified in Part 1 of the test, as they are crucial thermodynamic parameters that have to remain unaltered when we are trying to assess additional effects of PS. Thus, we can only aim to change Csat, for instance, by increasing the relative concentration of candidate components of X in the dilute bulk phase so that they would not join X, either because they prefer it less or because they prefer the dilute phase more. But how is Csat determined in a cell? We have powerful theories for the behavior of associative polymers in “poor solvent” conditions . Part 2 of the test should aim to gather hard evidence for PS. The general PS idea implies that a condensate will appear when the concentration of a putative PS driver exceeds in vitro aimed at deciphering its phase grammar and the rheological properties of the resulting droplets , beforein vitro with interacting parts capable of feedback control is a tremendous challenge that will project molecular mechanistic and synthetic biology into the future.The study of compartment biogenesis and organization should aim to reach the standards elucidated by work on the selective phase model , simulation and theory, microfluidics, and more. The challenges ahead are substantial and so are the rewards, which include our future ability to understand and control biological objects and subcellular compartments of enormous complexity, including our chromosomes and the machinery that mediates intercellular communication.


Themes varied across countries; however, identity, connection, balance and self-determination were common aspects of wellbeing. Having this broader understanding of wellbeing across these cultures can inform decisions made about public health actions and resources.Despite the health improvements afforded to non-Indigenous peoples in Canada, Aotearoa  and the United States, the Indigenous peoples in these countries continue to endure disproportionately high rates of mortality and morbidity. Indigenous peoples’ concepts and understanding of health and wellbeing are holistic; however, due to their diverse social, political, cultural, environmental and economic contexts within and across countries, wellbeing is not experienced uniformly across all Indigenous populations. We aim to identify aspects of wellbeing important to the Indigenous people in Canada, Aotearoa and the United States. We searched CINAHL, Embase, PsycINFO and PubMed databases for papers that included key Indigenous and wellbeing search terms from database inception to April 2020. Papers that included a focus on Indigenous adults residing in Canada, Aotearoa and the United States, and that included empirical qualitative data that described at least one aspect of wellbeing were eligible. Data were analysed using the stages of thematic development recommended by Thomas and Harden for thematic synthesis of qualitative research. Our search resulted in 2669 papers being screened for eligibility. Following full-text screening, 100 papers were deemed eligible for inclusion   Canada, Aotearoa  and the United States are all highly developed countries , yet theIndigenous populations across these countries live in substantially different social, political, cultural, environmental and economic contexts . SimilarIn order to make appropriate decisions about the allocation of public health resources to address health and wellbeing inequities, we first need to understand what aspects of health and wellbeing are valued by and relevant to Indigenous peoples. Understandings of health and wellbeing are culturally bound ,9. GlobaBox 1(1) Autonomy, empowerment, and recognition; which influences wellbeing through agency and self-determination of the individual and community;(2) Family and community; including kinships and notions of social and cultural connectedness; (3) Culture, spirituality and identity; which is interrelated and multidirectional; (4) Country; which is a holisticconcept encompassing identity, spirituality, culture, peoples, language, law and ceremony; (5) Basic needs; including food, money, housing and access to services; (6) Work, roles and responsibilities; both paid employment to meet basic needs and roles within community (including employment with Indigenous led companies);(7) Education; which presented as a complex relationship where tensions were felt between the need for formal schooling, and desire to pass on and learn cultural knowledge, and; (8&9) Physical health and Mental health (two separate themes); both encompassed a holistic understanding of health that is complex and culturally-bound.The current review was led by an Indigenous researcher from Australia (AG), with guidance from senior Indigenous researchers from Australia (GG), Canada (AK), Aotearoa  (EW) and the United States (MC). This review is part of a larger body of work that aims to develop a new instrument to measure wellbeing for Aboriginal and Torres Strait Islander adults, in order to more effectively inform decision making to improve health and wellbeing (the ‘What Matters 2 Adults’ Research Program ). The WMPeer-reviewed, indexed, and published papers that included Indigenous adults (18+ years) residing in Canada, Aotearoa  and the United States, and that qualitatively examined at least one aspect of wellbeing for a general (non-disease specific) Indigenous population, were eligible. There were no restrictions based on qualitative methodology or study quality.We excluded papers reporting an intervention or trial (where the focus was only on the outcomes), in which the findings applied only to a specific disease or condition, those that focused on young people under the age of 18, and those that focused only on health service delivery. We also excluded grey literature, poster abstracts, case reports, reviews, dissertations, books and book chapters, protocols, conference proceedings and presentations, and non-English papers.We searched titles and abstracts in CINAHL, Embase, PsycINFO and PubMed databases from inception to April 2020. Key search terms included Indigenous terms used in Canada, Aotearoa  and the United States, and wellbeing and quality of life terms see .n = 6). An additional paper known to the authors but not indexed in the included databases at the time of the search was also included (n = 1). After removing duplicates (n = 1556), the titles, abstracts, and keywords of 2669 studies were screened against the inclusion criteria using Rayyan online software for systematic reviews  essential for family well-being… [it is a] source of support that ‘bound individuals together’…”IdentityIdentity was reported by 18 papers as important to the wellbeing of the Indigenous peoples in Canada ,54,56,58Elders and grandparents said that healing occurs when cultural knowledge that is important to identity is passed down . Identit“…understanding who I am, who I am in terms of my family, my parents and my siblings, uncles, aunts and where I fit in the community, my relationships, aunts, uncles and all of that.”The impact of removal from one’s community and family was reported as negatively influencing some peoples wellbeing. In some papers, it was reported that those adopted or taken into foster care are reconnecting with their cultural identity ,38,49,53“It’s hard because we were raised white…But you know, I’m okay and I’m slowly learning more things about who I am—the connections and the boundaries.”LanguageThe importance of one’s Indigenous language, learning and knowing it, was reported by twelve papers ,49,53,54“…we believe that the language is the culture and the culture is the language and the two go hand-in-hand.”Family and community was reported by 31 papers as important to the wellbeing of the Indigenous peoples in Canada ,54,55,57“…talking to one or more others was essential to one’s well-being…talking was identified as the significant component of prevention, intervention, and healing.”Opportunities to be social and attend social engagements was reported as important to wellbeing; being able to connect with community during community events, regular group gatherings, performing cultural activities and sharing meals/resources were all seen to reduce issues associated with isolation and, in turn, build strong relationships ,43,46,47“…as a marginalized people, [we] have a very big void to address in that area… [people] may not even know they belong to a community. And when you’re isolated like that we all tend to go to the dark side so to speak. A healthy community is a strong community.”Supporting other community members was reported as important to Indigenous peoples in Canada ,45,51,53“…looking after children… many of those children are now adults who come to me to tell me I was good to them while they were young. It feels really good inside to know that they have not forgotten me. It’s a rewarding feeling.”Land and Sea, and the Physical, Mental and Emotional Wellbeing themes).An important way that the Indigenous peoples in Canada support each other and improve the wellbeing of the whole community is through the sharing of resources, especially food ,36,39,45“The meat was divided accordingly, nobody was left behind. The men would be up all night carving the meat, and people would come by to pick up their share… The people… were looking after the community.”Some papers reported that the wellbeing of the entire community required cohesion and self-determination, with strong leadership, guidance and teaching from Elders, and collective decision making that prioritised the needs of the community ,54,55,57“Home is living in a [healthy] community where there are elders to undertake (Indigenous) teachings in sharing circles and different ceremonies. This is what makes us who we are. We get our self-identity through communal living and the teachings that go on in the communities.”Family was reported by 20 papers as important to the wellbeing of Indigenous peoples in Canada ,53,54,55“[Family] provided acceptance and a sense of belonging, pride and respect… provid[ing] them with hope, knowing that they can always turn to a family member or friends for support.”“…culture [is] essential for family well-being… [culture] ‘bound individuals together’ via sharing food, sharing language, hearing Elders’ stories and going out on the land.”The concept of family for Indigenous peoples in Canada is broader than nuclear family structures. For Indigenous peoples, it extends to distant relatives, friends and chosen family , which provides an individual with a large and diverse support network, and, in turn, fosters and strengthens wellbeing ,39,47,49Elders were reported as being the cultural knowledge holders, and recognition of this was important to wellbeing ,45,53,55“But the times have changed a lot and the young people are now in a place where they don’t really know the old traditional ways but they know the new way more… And it’s due to the fact that the elder’s voices are starting to, you know, diminish…I want the young people to know that. Elders are an important part of their life.”vital” to the wellbeing of the Indigenous peoples in Canada  changes were described as disrupting hunting, fishing, foraging, trapping, and traveling to cabins because people were unable to travel regularly  due to dangerous travel conditions and unpredictable weather patterns.”“…culturally distinctive concepts of the person, the importance of collective history, the richness of Aboriginal languages and traditions, and the importance of individual and collective agency and activism”(p. 88 )“Although, there were clear power imbalances, the elders still perceived Aboriginal people to have some agency and power over their existence and cultural practices, resisting the encroaching European and ‘White’ dominance.”Stories of resilience were cited by 21 papers as important to the wellbeing of the Indigenous peoples in Canada, due to the effects of colonisation and how, through resilience, they have been able to protect collective history, culture and build the strength of the community ,54,55,57Resilience was especially evident in the papers that spoke about residential schools and the lasting impact that these negative experiences had on wellbeing ,38,53,54“…I dealt with all those hard emotional issues and began to build my life as someone with self-esteem… I eventually settled into who I was, my culture, and learned about residential schools and started a path of forgiveness for those that had harmed me.”Resilience was seen in acts of resistance to the rules imposed by residential schools, local authorities and the Church. Such rules were aimed at preventing the Indigenous peoples in Canada from engaging in spiritual and cultural practices ,53,54, w“They’d all take their bundles; their sacred items and they’d go up the river. Way up the river in the secret that’s where they’d do their ceremonies. They would never, ever do it in the community because it was against the law. You went to jail if you were caught doing those things.”two worlds ” was reported as important to wellbeing  try to balance those two worlds… And those [cultural] teachings have to come back in order to know who we are and how to balance ourselves.”Resistance against negative stereotypes and stories about the Indigenous peoples in Canada was said to be central in changing others’ perceptions of them, as well as for the identity and wellbeing of the Indigenous peoples in Canada themselves. “I really believe it’s important that our [Aboriginal peoples] story is accurately portrayed. New people to this country, as well as most Canadian citizens, need to know our story, need to understand the impacts of colonization and the residential school system on our cultures, history and languages, and the future impacts these will have for generations to come.”The Indigenous peoples in Canada’s spirituality and cultural medicine were reported by 18 papers as important to wellbeing ,54,56,58Cultural medicines, due to their holistic nature and ability to heal spiritually, were important in healing and wellbeing ,46,56,58“…traditional healers [are] holistic practitioners, addressing body, mind, and spirit, which [is] different from the Western approach….”the Creator” and “Mother Nature”, was described by some as the foundation to wellbeing  can ensure younger whānau have an embodied and emplaced experience of their belonging in this place as their tūrangawaewae (place of belonging).”Iwi  control, self-determination and autonomyIwi control, self-determination and autonomy were described as important to the wellbeing of Māori  or politics are always running these [health care systems], I don’t know if we’re going to get any better.”kotahitanga to Māori wellbeing was reported by 13 papers  a spiritual connectedness… with the land and the environment in which I live… It just makes me feel whole, and complete… my maunga (mountain) and… my awa (river)… directly affect my mental health and my physical health….”In one paper, Māori healers outlined how transgressions against the land directly affect the health of the individual . The int“…also understanding the relationship between the health and wellbeing of ourselves as people and the health and wellbeing of our lands, of our rivers, of our oceans, of our mountains, of all of the environment. So, I think there are definite links between the health and wellbeing of people and the health and wellbeing of our environment.”Kaitiakitanga was also described as important to Māori relationships with people, fostering stronger ties between people and building Māoritanga (identity) , manaakitanga [practising respect and kindness] and I think I’m here for the well-being of the people.”Whanaungatanga was described as being built and maintained through tauutuutu (reciprocity) and mana (respect), which, in turn, were said to produce positive impacts on the wellbeing of the individual practicing these customs … it would mean I’d be able to just do more with my daughter and my partner…”kaumatua (elders) and the vital role they play in the wellbeing of the whole whānau, hapu (sub-tribe) and iwi (tribe) as pillars of tradition and living links to whakapapa   it doesn’t happen [Indigenous custom] it makes me feel uneasy, like something’s not right… they [non-Indigenous people] didn’t do a karakia (Indigenous prayer/incantation)… and that made me feel different….”Of the included studies, 41 ,118,119 n = 10 papers); Culture (n = 30); Spirituality and Cultural Medicine (n = 28); Tribe/Community and Family (n = 29); Land, Sea and Subsistence-based living (n = 28); Resilience (n = 21); Basic Needs (n = 17).Our analysis of the included papers revealed seven interrelated aspects of life as being centrally important to the wellbeing of Indigenous peoples in the United States: Holism  and the consequent relationship disharmony ,92,115, “[through attempts to] Christianize and civilize and assimilate our people, we lost a lot. There’s some generations where some of our people weren’t able to learn the language, weren’t able to learn a lot of things about who we were, our traditional ways… That’s where we lost many of our values and cultural ways… pretty much forced into the assimilation.”Enculturation  was described in 17 papers as important to overcoming acculturation, which confer a renewed sense of pride and identity ,116,119.“reawakening of our people… to not just understand, but value what we know as Native people, and how that’s instrumental to where we want to go in the future… [thus] strengthening the wellness of the individuals [and] community wellness.”Passing down cultural knowledge through storytelling, mostly by Elders, was reported by 19 papers as important to cultural preservation and wellbeing ,116,118.“The Elders… teaching [the youth] traditional values and lifestyles and incorporating Western technology with subsistence activities, all of which contribute to their emotional well-being.”LanguageThe importance of one’s Indigenous language to the wellbeing of Indigenous peoples in the United States was reported by eleven papers ,107,116.“When asked why language is so important Alayna replied, ‘it’s really important to our overall health and well-being. It has everything to do with who we are and we’re getting further and further away from that.’…”“I feel sad because I don’t speak Navajo, I know that I lost something.”Physical ActivityPhysical activity was reported as important to the wellbeing of Indigenous peoples in the United States in the context of culture (including Tribe/community) by seven papers ,118,119.“Even moderate exercise, such as staying busy in the community or engaging in subsistence activities, helps improve quality of life, both mentally and physically….”Spirituality and Cultural Medicine were reported as important to the wellbeing of Indigenous peoples in the United States by 28 papers ,118,119.“[United States Indigenous Peoples’] emphasized the belief that the path to true wellness and health implies matters of not only physical well-being, but functions of spiritual and mental health as well. Inherent in this idea of holistic balance is that traditional medicine is one of the primary pathways to restoring the imbalance….”Higher Power or EnergyThe belief and connection to a higher power, or energy, were reported by 14 papers as important to the wellbeing of Indigenous peoples in the United States ,111,113.“The Holy People are understood to play a crucial role in the efficacy of the ceremony and in maintaining one’s health and well-being throughout life.”“Ceremony and language remind people of ‘how all is a part of me and we are all a part of this,’ including nature and connection to higher powers, and how the continual work to ‘restore balance’ ensures the wellness of all parts.”Cultural MedicineCultural medicines, including ceremonies and dances, were reported as important to the wellbeing of Indigenous peoples in the United States by 19 papers ,111,119.Ceremonies were reported as important due to their use in Cultural Medicine, connecting and reconnecting to each other, and giving a sense of identity (particularly when displaced from home) ,107,111.“After our community performed this ritual we felt a difference among each other and in our homes and lives. We all felt lighter and happier. We smiled at each other more easily and things got better for our young people. The ritual brought us together and together we were stronger.”Cultural dances were reported as balancing the four aspects of wellbeing , giving “I see a really great relationship between hula and health in all aspects of health, not just physical health, but mental and emotional health, spiritual health…” Tribe/CoCommunity and family were reported as important to the wellbeing of Indigenous peoples in the United States by 29 papers ,118,119.Tribe/Community was reported as important to the wellbeing of Indigenous peoples in the United States by 26 papers ,118,119.Connection to Tribe/community, which included having Tribe/community support and safety, is an important aspect of wellbeing ,118,119.“Relationships provide a connection within community as well as an avenue through which to develop identity, both are important concepts….”Elders in the Tribe/community were reported as important to the wellbeing of Indigenous peoples in the United States by 15 papers ,113,119.“kūpuna (Elders)… pass down culture, religion, values, in the right way to the next generation… kūpuna looks to the past and future. Kūpuna are the ones with the knowledge—wisdom. They respect Hawaiian values and deserve respect.”is an active kinship system inclusive of parents, children, cousins, aunties, uncles, and grandparents”, and can include “close, trusted friends”, which is an important distinction for Indigenous peoples in the United States when compared to the greater emphasis on the nuclear family in Western cultures .”“Gaining independence enhanced the well-being of many participants… Learning to adjust was essential for participants who maintained well-being.”Basic needs were reported as important to the wellbeing of Indigenous peoples in the United States by 17 papers ,117,118.Money and employment were reported together, with other aspects of having employment not reported as being as important as earning ,117,118.“Not having to fret about simple things like food. To be able to not lavishly but comfortably do things you’d like to do. Basically that everyone is healthy. I don’t really look at it so much as status but I mean, just being financially sort of stable… Well-being is a roof over our heads, clothes on our backs, food in our stomachs, and our health.”“Her jobs were demanding, stressful, and took away from family time, all of which may have contributed to diminished well-being.”Services, both health and social, were considered important to wellbeing, specifically physical and mental health ,117,118.“For most of the participants, it was best if the care provider was Hawaiian or knew Hawaiian ways and respected Hawaiian culture.”identity, connection, balance and self-determination, were found across countries.Our analysis of the literature identified seven themes of wellbeing of Indigenous peoples in Canada, five themes in Aotearoa  and seven themes in the United States see . While widentity was strongly linked to Indigenous peoples’ connections with family, Tribe/community, culture, the land, genealogy, and spirituality. It has been argued that these interconnected aspects of identify are integral to Indigenous peoples’ wellbeing and disruption to any of these aspects can be detrimental to Indigenous people both individually and collectively [acts of renewal” [In this review, ectively . In thisrenewal”  and, alorenewal” .balance of one’s mental, physical, emotional and spiritual aspects of life was seen as fundamental to Indigenous peoples’ wellbeing. Indeed, while we have separated these and other elements of wellbeing into somewhat artificial themes, it must be noted that they are interconnected and need to be considered in conjunction with each other to understand wellbeing for Indigenous peoples. In some of the included papers from Canada and the United States, Indigenous peoples’ wellbeing was conceptualised within the Medicine Wheel and its teachings. The Māori peoples of Aotearoa  had a similar underlying philosophy of wellbeing that also includes whakapapa . Whakapapa encompasses connections between people, places, and times, thus linking family, land, and ancestors. Indigenous people in Canada and the United States spoke about the importance of these and described family, land and ancestors as underlying other themes of wellbeing, despite not arising as a distinct theme in itself.Similar to the findings of the Australian review , we founSelf-determination is a central element of wellbeing for Indigenous peoples [our homelands will recognise us as being Indigenous to that place” and future generations will have the freedom to “live more Indigenous lives” [ peoples ,122, a f peoples ,124, for peoples . In the traditional”, being holistic in nature, with the health of the whanau (family), hapu (sub-tribe) and iwi (tribe) stated as important [While there were commonalities in the themes across the three countries, it is important to note where the experiences of wellbeing diverge. For example, when looking at basic needs for individuals and Tribe/community, the Indigenous peoples in Canada and the United States reported very similar needs including adequate housing, food security and the need for culturally safe services. In Aotearoa , Māori people did not directly report these things as being important to their wellbeing—rather, only mentioning basic needs within the context of relationships and social networks, and how these important connections facilitated these needs. This finding echo’s those of Cram and colleagues (2003) who reported Māori conceptions of health were “mportant . This fomportant . This isThere was an undercurrent of experiences with racism, particularly systemic and institutional racism, along with discriminatory practices that impede wellbeing in some of the included articles. This was particularly evident in terms of resilience and resistance (Canada and the United States) and also in terms of impact ). Investigating this phenomenon and its impact on wellbeing warrants examination as a primary aim of future research.Our review highlights the importance of understanding what constitutes wellbeing for Indigenous people. This is particularly so when developing policies and programs to achieve equity across populations. Our findings suggest wellbeing for Indigenous peoples is not completely congruent with Western biomedical views on health and wellbeing, which underpin most current measures of health and wellbeing. Angell and colleagues (2016) conducted a global systematic review of quality of life measures among Indigenous populations, and reported that only 3 out of 41 studies used Indigenous-specific measures . There iAn important limitation of our study is the exclusion of grey literature. This decision was made pragmatically due to the already large scope of this review. However, as community-led projects are not always published in peer reviewed journals, the current review may not have captured these studies, nor the aspects of wellbeing reported in these. Future reviews on the topic of wellbeing in Indigenous peoples should consider inclusion of grey literature from the included countries and this should occur under the guidance of an Indigenous person from the respective country. Additionally, we note that we have included studies in our review that were led by Indigenous and non-Indigenous investigators. We recognise that this may have resulted in a somewhat different understanding of what wellbeing means to Indigenous people compared to if the review had focused exclusively on Indigenous-led studies. However, our review was led by an Indigenous Australian researcher and included guidance from senior Indigenous researchers from Australia (GG), Canada (AK), Aotearoa  (EW) and the United States (MC), particularly around the interpretation of findings related to their respective countries. The methods used to identify the themes described in this paper would have benefitted from having input and guidance from Indigenous peoples from the included countries from the outset. However, due to the COVID-19 pandemic and the timing of the data analysis, this was not feasible. We recommend that future reviews on Indigenous health including wellbeing be led by Indigenous persons from the respective countries, from the design through to interpretation and dissemination of findings.Our review identified several themes of wellbeing important to Indigenous peoples in Canada, Aotearoa  and the United States. While there were some commonalities between countries, our findings reinforce the understanding that the experiences, priorities, and needs of Indigenous peoples in different places are unique and specific to local contexts. We reiterate previous findings that the conceptualisation of wellbeing for Indigenous peoples goes beyond that typically measured in quality of life measures . Wellbei


While scientific pluralism enjoys widespread popularity within the philosophy of science, a related position, epistemic relativism, does not have much traction. Defenders of scientific pluralism, however, dread the question of whether scientific pluralism entails epistemic relativism. It is often argued that if a scientific pluralist accepts epistemic relativism, she will be unable to pass judgment because she believes that “anything goes”. In this article, I will show this concern to be unnecessary. I will also argue that common strategies to differentiate relativism and pluralism fail. Building upon this analysis, I will propose a new way of looking at both positions’ relations. This article aims to understand what explains the friction between scientific pluralism and epistemic relativism. I will demonstrate that conceptualizing both epistemic relativism and scientific pluralism as “stances” sheds better light on their relation and demonstrates that it is, in principle, possible to support both positions at the same time. Preferred policies and levels of analysis, however, cause friction in practice. Historian of science Lorraine Daston recently observed that relativism is one of the “ghouls and goblins allegedly let loose” by Thomas Kuhn, which today barely elicits a yawn Daston , p. 119.Dependence: the epistemic status of a belief is relative to (a) an ES, or (b) a bundle of precedents, judged as virtuous;PluralityNon-Absolutism: none of these ES or bundles are absolutely warranted;Exclusiveness: some of these ES or bundles can be exclusive , either because (a) they give different yes/no answers to the same questions (questions about the epistemic status of a belief) or because (b) they involve incommensurable forms of action;Symmetry: ES or bundles are to be treated symmetrically because either (a) they are only based on local reasons for credibility, or (b) there is no neutral way of ranking them or (c) they are all equally good,5Conversion: switching from one ES to the other is not possible nor plausible by rational comparison;Semantic Relativity: the statement “A subject S is epistemically justified believing p” expresses a proposition of either one of the two forms: (a) as per the ES or the bundle I (the speaker) am based on, is S epistemically justified to believe p  or (b) S is epistemically justified to believe p. This proposition is relatively false or true, depending on the contexts of assessment. (semantic relativism);Metaphysical implications: (a) factual understanding: to be epistemically justified is a real relation between convictions and other factors. Epistemic relativism is the thesis that ES or bundles are a central component within this relation; (b) non-factual understanding: epistemic relativism is no metaphysical but a language-philosophical thesis.SP and ER are quite common notions within philosophy and the philosophy of science in particular. There are, however, many definitions of SP and ER, respectively. Let me thus immediately define what the terms ER and SP will denote in this paper. Philosopher and sociologist of science Martin Kusch provides a “standard model of relativism,” which surveys eight criteria collected from definitions given by friends and foes of relativism Kusch , p. 107fThe Pluralist Stance  several theories, explanations, or methods to approach the same natural phenomena.Acceptance: plurality is favorable.For a definition of SP, I will rely on Steven Kellert’s, Helen Longino’s, and C. Kenneth Waters’ “pluralism-manifesto” t Stance . While nThe question regarding the relation of SP and ER is asymmetrically discussed in the SP and ER literature, respectively. The issue of whether SP entails ER is prominently addressed by scientific pluralists. This is not the case for the ER literature. Several articles consider plurality or pluralism a component of ER  and argue that the relativist does not renounce judgment. Understanding the differences between SP and ER by reference to RoJ, therefore, fails. Second, I will examine another strategy to differentiate SP and ER: the introduction of epistemic values. Several card-carrying scientific pluralists argue that their pluralism does not entail ER because they maintain the possibility to choose between theories. They preserve judgment through the introduction of epistemic values. I will argue that this strategy fails to clear SP of ER because epistemic values introduce relativism on the level of value choice.Third, having shown that the two most common strategies to differentiate ER and SP fail, I will examine ER and SP in detail. I will argue that pluralists often do not support “symmetry” or “exclusiveness.” Relativists, on the other hand, might not support the pluralist’s “acceptance” or “non-monism.” Thus SP does not “entail” or “lead to” ER. There are, however, some forms of SP that are compatible with some forms of ER, but there simply is no one-dimensional relation between both positions.there is no reason why SP would entail ER, but there are versions of SP that are compatible with ER, and ifthe most prominent “fears” of scientific pluralists regarding ER turn out to pose no threat ultimately,then why are card-carrying scientific pluralists that concerned to maintain a boundary between SP and ER? I will put forward the idea that differences in commitments or preferred policies cause disagreement between pluralists and relativists. These differences also account for the intensity of the disagreements. If the main differences lie in commitments, values, emotions, and policies (VEPPs), looking at necessary and sufficient criteria might not be the best way to understand similarities and differences between SP and ER. I will argue, following Kusch  judgment is possible. The epistemic relativist believes that it is possible to pass judgment on one or several ES. She would, of course, declare this judgment as situated within the context of her ES. Nevertheless, the epistemic relativist can pass judgment and rank different ES by referring to her ES. To her, a statement does not lose its normative content once it is situated. Quite to the contrary, relativized assessments are all that can be. In conclusion, the relativist does not renounce judgment. She only renounces the possibility of absolute, neutral judgment  are equally valid Crasnow , p. 139.It is, however, essential to note that the relativist only discourages the ranking of systems when referring to absolute criteria . In their manifesto, they hold that pluralists, but not relativists, can pass negative judgment on “instances of bad research.” Kellert, Longino, and Waters do not spill much ink on which values they have in mind particularly. Thus, I will consider Longino’s discussion of values in her paper nowledge .Longino lists six feminist values that should guide theory choice. These values limit plurality by excluding “instances of bad research” . The first value is “empirical adequacy”: “agreement of the observational claims of a theory with data” (ibid.). Received and feminist sets of values share empirical adequacy. Longino emphasizes that empirical adequacy is not sufficient for theory choice. One of the classical problems regarding empirical adequacy is the underdetermination of theory by data. Underdetermination suggests plurality: more than one theory might be empirically adequate. The monist needs to resort to other values to limit the choice to one theory. The pluralist is content with a less restrictive choice, as she need not eliminate underdetermination but only keep out specific theories.The additional values Longino proposes are novelty, ontological heterogeneity, complexity of interaction, pragmatic dimension of knowledge, and decentralization of power .Longino’s proposed values are a case in point for a set of values that might not be embraced by all philosophers of science or scientists. Some philosophers might insist on the superiority of the “traditional” values and prefer their realization over Longino’s values. For example, scientific pluralist John Dupré proposes epistemic values that resemble the traditional values closely.Most epistemic values are highly desirable. Yet one’s personal preferences and agendas define which values one gives priority. My review of two sets of values, the canonical and Longino’s feminist values, demonstrates the vast heterogeneity of values pluralists might put forward. If we look beyond the scientific pluralism literature and towards more “canonical” surveys of values, even more agendas are in view. A standard scientific realist account of values would, for example, prefer only those values that promote the truth of particular scientific theories . Let us consider, for instance, a normative pluralist position. Symmetry might be negligible to the normative pluralist. She could maintain that there is one, single, and absolutely best ES/approach. But she could still cherish the benefits of having more than this one. For instance, she could point to certain benefits of keeping more than one system or approach around. Chang’s benefits of tolerance and interaction would be famous examples of such benefits Chang , p. 279fAnother example is “exclusiveness.” Some versions of SP do not consider the presence of several ES. Such versions of SP describe theories or explanations within a framework considered one ES . Van Fraassen claims that one should understand philosophical positions as stances. A set of VEPPs characterizes particular stances.This section aims to investigate whether framing ER and SP as stances provides better clues regarding these positions’ differences and similarities. In so doing, I will survey their respective VEPPs. First, I will assess the possible benefits and drawbacks of this approach. If van Fraassen is right, conceptualizing positions as stances helps to understand the core of these positions, distill differences, and crystallize disputes between stances. As the focus lies on commitments such as values, policies, and emotions, the approach might reveal disagreements that do not play out fully when analytically comparing two positions but cause friction in practical settings. It is, however, not clear why one should focus on VEPPs and not on the very credo or dogma of a position Kusch .15 WhethI will select one version of ER and one version of SP to capture them as a stance: I chose David Bloor’s Sociology of Scientific Knowledge (SSK) as a paradigm approach for ER .SSK policies resonate with the value of epistemic humility: we should not lay universal claim to rationality or truth. Epistemic humility can be understood as a rebellion against any form of absolutism in metaphysics, epistemology, or ethics. Besides epistemic humility, SSK encourages tolerance and equality. SSK emphasizes group processes as explanatory for the phenomena described: there are different codifications of our reasoning properties, defined by interests and negotiations of different groups. SSK scholars summarize this doctrine as “normative rationality.” . Also, they focus on scientific endeavors as group processes and do not highlight the work of individuals. Besides, they emphasize the vast diversity of group processes within science.As pointed out above, PS suggests the policy of empirical testing. As a result, the authors of PS reject particular philosophical positions, especially fundamentalism and monism, if these are founded on metaphysical prejudice. They also reject specific versions of SP. On the one hand, they reject “modest,” SP. “Modest pluralism” holds that it is possible to reconcile various approaches in one way or another. On the other hand, they reject “radical” pluralism, that is, pluralism that is anti-realist, or pluralism that supports an “anything goes” vibe. The authors of PS fault the “equal validity” thesis, and they fault demolishing opponents based on metaphysical prejudice (monism) (2006). Longino, in addition, faults androcentrism and other behaviors that promote inequality.PS favors a “tamed realism.” Kellert, Longino, and Waters discourage strong metaphysical presuppositions regarding what the nature of the world is like and whether any of our positions, be it monism or pluralism, can answer this question . They enAnalyzing both SSK and PS as stances  empiricism. Both stances engage in boundary work to demarcate their position from related positions. SSK strongly emphasizes its rejection of the “weak program,” whereas PS rejects “modest” as well as “radical” pluralism. While SSK rejects absolutism, PS rejects fundamentalism, monism, and relativism (explicitly referring to SSK). To be precise, PS rejects the “equal validity” thesis of relativism.One key difference is the proposed policies and the level on which policy applies. SSK’s policy determines how to do social science. PS’ policy operates on the meta-level (how should philosophers think about science) and on the level of the empirical sciences (which approaches should be pursued by researchers). In this sense, it is possible to discern a difference in the levels of analysis. SSK is a doctrine on how to collect and analyze data regarding particular scientific episodes and which types of explanatory strategies should be employed. PS demands the philosopher to have a particular outlook on the empirical sciences and also requires a similar commitment of scientists: PS demands the introduction of more approaches and empirical assessment of these approaches. This task will not lie on the shoulders of philosophers alone. From the perspective of the SSK-er, the absolutist claim that scientists and philosophers should adopt a particular epistemological position is a no-go. For the defender of PS, discouraging the PS’s normative approach towards changing scientific inquiry means to negate the policy that is dearest to proponents of PS.In conclusion, portraying SSK and PS as stances highlights similarities and differences. SSK and PS share a commitment to empirical input, particular virtues, an admiration for science and plurality displayed in science. PS’ rejection of “anything goes” needs to be mentioned as a difference. Having shown, however, that the “anything goes” argument is a strawman, I do not believe that this rejection should receive center stage regarding the aspects that differentiate both positions. It thus does not come down to principled rejections of specific necessary and sufficient criteria. The most noticeable difference is the particular policies SSK and PS champion. These different policies make visible the different emphases of the respective stances and what, exactly, each stance’s proponents would like to see changed about philosophy, sociology, and science. It is this disagreement about policy and the level on which policy should apply that causes real-life friction and the difficulties individual proponents of PS and SSK might have with each other.Disorder of Things, John Dupré proposes a version of pluralism that places purpose-sensitivity  as its central motivation (Analyzing SP and ER as stances or analyzing them as done in the last section leads to partly similar, partly different results. There is no reason why SP and ER would not go together in principle. To combine both ER and SP in one’s position, certain VEPPs need to be sufficiently similar. Paul Feyerabend’s early and late epistemological anarchism is an example of a position that admits both SP and ER Kusch . There ativation . As a reWhat becomes clear through understanding SP and ER as stances is that SP and ER have a different agenda most of the time. ER and SP commit to partly similar and partly different VEPPs. For SSK and PS, what differentiates both stances most, is a difference in policy. Deep disagreements about a particular policy cause strong responses of scientific pluralists against ER in the literature. These policy differences are, however, seldomly addressed, and arguments for repudiating ER such as RoJ or “equal validity” are invoked instead.Whether SP and ER “go together” in one philosopher’s position is thus a matter of emphasis and ranking of particular VEPPs. Take philosopher and historian of science Hasok Chang as an example. In earlier works, Chang emphasized his rejection of relativism , 2015. IThis brings back a more general notion about the difference between SP and ER: the level of analysis. SP usually characterizes positions that operate on the level of the empirical sciences , while 18Introducing the idea of the “stance” and “VEPPs” also weighs in on the relativist’s rejection of RoJ. Different ES might share certain VEPPs but might not share others. Proponents of different ES will rank some of the shared VEPPs differently in importance. In a situation when the epistemic relativist compares her ES with another ES, she will discover that certain VEPPs her ES ranks high might not be that important in the other ES. On the other hand, she will find out that the other ES ranks particular VEPPs high, which she considers less important.If she values a particular policy but sees this policy not valued in a different ES, why would she say “whatever” Chang ? The facThe choice of possible VEPPs is vast. I argued that some of these might contradict each other or cannot be embraced simultaneously. Thus, there needs to be a choice—choice of a particular set of VEPPs over another. I pointed out that this choice is informed by other commitments, for example, in the case of feminist philosophy, the policy to rid science of androcentric theories Harding . In the Viewing one’s choice of epistemic values as part of one’s stance also brings home the idea of these values’ intrinsic relativity. The defender of one particular assortment of VEPPs might realize that the assortment of, say, another scientific pluralist does not resonate with hers. She would, of course, not believe that she cannot pass judgment or believe that both sets of VEPPs are “equally valid.” Take the feminist philosopher, for example. Why on earth would she believe that a particular system that does not rank specific values highly, that she believes are crucial for criticizing androcentric theories, is as good as hers, with respect to her system? She would, of course, also believe that it would be better if that other system ranked values differently. But she will also realize that she might not be able to convince a proponent holding on to a different ranking of VEPPs.In this article, I aimed to explore the relation between SP and ER and understand points of friction. I believe that I have shown several things. First, RoJ is neither part of ER nor of SP. Second, the introduction of epistemic values guides theory choice but cannot set apart SP from ER because it introduces relativism on a different level. Third, SP does not necessarily entail ER and vice versa. Fourth, applying the perspective of the stance, similarities and differences of both positions become discernable. If emphases are sufficiently similar, it is possible to support ER and SP. It is possible to be a relativist and a pluralist at the same time. Being a relativist pluralist is not epistemologically pernicious. It determines a particular stance, with particular choices of VEPPs. Disagreements about emphasis and policy set some epistemic relativist positions apart from some scientific pluralist positions. Disagreement about such policies brings about strong responses against ER. While there are no principled reasons why SP and ER cannot go together, policy differences often prevent accepting both positions in practice.


A rich body of studies in the human and non-human literature has examined the question how novelty influences memory. For a variety of different stimuli, ranging from simple objects and words to vastly complex scenarios, the literature reports that novelty improves memory in some cases, but impairs memory in other cases. In recent attempts to reconcile these conflicting findings, novelty has been divided into different subtypes, such as relative versus absolute novelty, or stimulus versus contextual novelty. Nevertheless, a single overarching theory of novelty and memory has been difficult to attain, probably due to the complexities in the interactions among stimuli, environmental factors  and level of prior knowledge but see . Here we For example, imagine you live and work in an urban area and you take the same route to work in your car every morning. One day you see a flock of sheep blocking the road on your commute. You will probably remember this event for a long time, while the other countless times you have driven down that road are forgotten. Numerous studies have confirmed this observation, namely that if we experience a novel event in a familiar context, we tend to store and remember this event more easily. However, if you happen to live in the countryside close to a sheep farm, your experience might be quite different: because you see flocks of sheep quite frequently, you might experience just another regular commute to work that is hardly memorable. Thus, the experience of novelty is not ‘absolute’ and cannot be defined independent of the observer; rather it is driven by what an individual expects to experience compared to what they actually encounter. This comparison between expected and experienced outcomes parallels the computation of a prediction error (PE) in many theories of learning. According to such theories, we continuously generate expectations about our environment, and update those predictions when they are wrong, i.e., when a PE occurs. While this role of PE in learning is well established in experiments on non-declarative memory , its role in human declarative memory According to PIMMS, memory and perception arise within multiple levels of a processing hierarchy, where higher levels are constantly predicting the activity in lower levels, and the difference between the predicted and actual activity (at a single moment in time) – the PE – is fed back from lower to higher levels. For a given layer, the predictions from the level above are equivalent to a “prior” probability distribution (in a Bayesian sense), whereas the activity profile (produced from the level below) is equivalent to the evidence or “likelihood”, while the PE is the Let us consider a level representing the current items perceived , which may or may not be predicted from a higher level representing the context . Take the example of sheep encountered in an urban environment: the context is predicting houses, road-signs, other cars, etc., whereas the sensory input is indicating sheep. This corresponds to a prior and likelihood that are quite precise but differ in their modes A. This r2Now consider another situation, where you enter a new environment (a context that you have not experienced before), then you have minimal predictions about what items to encounter, such that the prior is imprecise, or in the extreme case, “flat”. We will call this “context novelty”. When you do encounter a familiar object (such that the likelihood is precise), there is still a PE ; a “semantic” level, which contains knowledge about individual items and their corresponding configuration of perceptual features; while lower in the hierarchy, “perceptual” systems represent individual, modality-specific features of the stimuli.The key function of the episodic system is to optimize the predictability of an item occurring in a particular spatiotemporal context, i.e., store context-item associations. When we encounter a familiar item in a context that is different from that expected, the ensuring PE induces learning of more accurate associations between episodic and semantic representations. This is the type of learning that enables memory of the spatiotemporal context in which an item occurred, or what has been called “recollection” . This epThe semantic level on the other hand stores information about familiar items, and predicts which features are expected on the basis of a given item being present. Note that there is a bidirectional flow of information between all systems, so not only do currently active item representations make predictions about associated perceptual features, but currently active features also influence which item representations remain active . The semantic system is associated with anterior temporal lobe regions, including perirhinal cortex, and it is the strengthening of item-feature associations that enables the feeling of “familiarity” (rather than recollection), which sometimes accompanies recognition memory .There are probably numerous levels of intermediate perceptual representations, depending on the modality, but for simplicity we consider posterior temporo-occipital regions associated with perception of visual stimuli. However, since we focus here on declarative memory, we will concentrate on the episodic and semantic systems.Given this brief overview of PIMMS, we summarise different types of novelty/surprise in 3Context surprise is the most studied form of novelty in the human psychological literature. Going back to our initial example, the context we are in (being on the way to work) predicts the presence of certain objects and events. If we now encounter something that is not predicted, like the sheep, then the resulting difference between prediction (the prior) and observation (the likelihood), give rise to a PE, which triggers the formation of an episodic memory for this unexpected event.3.1We start with what has been called the classic ‘novelty effect’ in episodic memory . In thisHowever, the cause of this ‘classic’ novelty effect has been challenged by alternative explanations, other than a special role for novelty in encoding, such as distinctiveness or source confusion at retrieval . In geneHow is this novelty-encoding effect explained by PIMMS? One possibility relates to predictions made by the temporal context. When you encounter the list of random words in the familiarisation phase, you are unable to predict the next word. However, in the critical phase, you notice that some of the words are repeated from the familiarisation phase, so you might start to expect further repetitions. Indeed, if novel items become less expected, they will elicit a greater PE than the familiar words, and therefore become more strongly associated with the context of the critical study phase (hence an example of context surprise). Therefore, when finally asked to recognise words specifically from that phase, you are better able to do so. If this interpretation is correct, then the advantage of these “novel” words should depend on the strength of expectation for repeated words, which could be tested by manipulating the ratio of familiarised to new words in the critical phase. This prediction is consistent with 3.2Another long-standing line of research also uses repetition to build up expectations within the course of the experiment. However, rather than using temporal context to drive the expectation of pre-familiarised items, as in 3.3Other studies have varied the strength of predictions by training associations or relations between items. For example, In a later study, While the above studies are consistent with a general pattern of PE driving declarative memory, they also illustrate a limitation of PIMMS, in that it remains unclear what is generating these predictions, since the predictions from trained rules or item-item associations do not obviously come from the spatiotemporal context, nor from (pre-existing) semantic knowledge. The fact that the greater PEs lead to better recollection e.g.,  suggests3.4unsigned PE (in the context of PIMMS), but with RPE, because the reward has a direction (more or less), one can additionally distinguish signed RPE, i.e., positive when the actual reward is bigger than the predicted award, and negative when the actual reward is less. Although the literature on RPE has typically focused on non-declarative learning (e.g. Another method is to establish predictions for a reward following a stimulus. In the human literature on such “reward PE” (RPE), a stimulus (or class of stimuli) is typically repeatedly paired with a reward , so that future presentations of that stimulus lead to the anticipation of reward, and a RPE is triggered if the reward is not delivered D. Intereing e.g. , RPE caning e.g. . Jang eting e.g. . The rel3.5In the studies discussed so far, predictions were constructed ‘online’ within the course of the experiment and the results generally endorse the view that contextual surprise enhances memory. In real life, however, context surprise is more likely to arise from expectations that were established over an extended period of time, and some studies draw on this real world knowledge as a source of predictions.For example, 4An example of item surprise would be encountering a pink sheep, i.e., a familiar object that has most of its expected features except for a few unexpected ones B. AccordThese situations demonstrate that novelty/surprise is not the only factor that drives declarative memory encoding, and that sometimes, congruency with prior knowledge (or a “schema”) can boost memory encoding too, even though this is a situation with low PE as in E. This c5Context novelty, rather than context surprise, refers to a novel context that makes no clear predictions. This describes the situation in many laboratory studies of memory for random lists of items, where there are minimal predictions about each item before it appears. Though PE is not as high as in the cases of surprise above, where there are (incorrect) predictions, PIMMS still predicts higher PE for familiar than novel items , even if that other information is relatively unrelated and not necessarily novel itself. Let us return to our example in which you encounter a flock of sheep on your way to work, which was highly surprising. There is good evidence that you will remember this event better than other morning commutes. However, what is it that will be stuck in your memory? Is it just the unusual event of seeing sheep, or will you show a benefit for other contextual information that was present at the same time, such as what song was playing in the radio, what clothes you were wearing or whether the sun was shining? In addition, are you also more likely to remember other moments that happened right before or after the encounter of the sheep, such as whether you did the school run that morning or with whom you had a meeting once you arrived at work?7.1One related question for PIMMS is whether PE only enhances learning of associations between the predictor  and the predicted (e.g. features) – i.e. learning that is “local” to the cause of the PE – or does it trigger a “global” increase in learning which also enhances memory for other incidental information that happens to co-occur with a PE? An example of memories that contain rich incidental, episodic information are “flashbulb” memories, which lead to clear recollection of the context surrounding a particular event, such as where one first heard the news of the 9/11 terrorist attacks . FlashbuIn mundane laboratory studies, this incidental contextual information is often called “source information”, which can range from where on the computer screen an item was presented, to the mental thoughts that occurred at the same time . For exa7.2The previous section considered the effect of novelty on simultaneous source information. However, what about information experienced shortly before or after a novel event? There is evidence that novelty can exert a beneficial effect both retroactively and proactively, so as to “spill-over” to stimuli that are not novel themselves, but are simply encountered in close temporal proximity. This effect, inspired by the synaptic tag and capture theory  was firs8In addition to how well we remember information, novelty and surprise also appear to play an important role in parsing or segmenting our continuous experience. In contrast to most laboratory experiments that show discrete events/items/trials, our experiences in the real world are derived from a continuous stream of sensory input, during which our brains are constantly trying to predict what will be perceived next. According to “event segmentation theory” , sudden This notion is supported by 9So far, we have talked about the behavioural predictions of PIMMS. There is also a wealth of neuroimaging studies on humans  that address the brain regions involved and/or the temporal dynamics of novelty effects, and an even larger literature on animal studies of the neurobiology of novelty and memory. We only scratch the surface of these literatures here, in an attempt to bring out the clearest findings in relation to some of the distinctions outlined in the previous sections.9.1Context surprise has consistently been associated with the medial temporal lobe (MTL), and the hippocampus in particular, across a wide range of neuroimaging studies e.g. . StrongeThese findings are in line with the PIMMS framework, which predicts strong hippocampal activity for context surprise A, and thStudies that use event-related potentials (ERPs) to examine context surprise, report deflections of a central-parietal ERP component known as the P3, elicited 300–400 ms after stimulus onset e.g. . StrongeIn addition to context surprise, PIMMS predicts hippocampal activity for context novelty or item novelty, albeit lower, since it is driven by a smaller PE than for context surprise . This haOther ERP studies have examined item novelty. For example, a study by 9.2So far, we sought to explain how novelty and surprise determine the fate of new declarative memories through the lens of PIMMS. Although PIMMS offers a framework for thinking about novelty and surprise, as well as making predictions for behaviour, it remains largely silent as to what brain mechanisms, neurotransmitters and molecular processes might underpin such behaviour. These mechanisms have been addressed by several neurobiological models of novelty and surprise in the animal literature. However, it is often difficult to reconcile those models with the data reviewed above, because of disparities in the terminology and nature of the paradigms used in the animal and human literature see also .In line with human neuroimaging studies, most models propose that the hippocampus plays a central role, but make different claims about the neural circuits involved in processing novelty and surprise. On the other hand, Interestingly, an influential framework  suggestsMany of the models mentioned so far base their assumptions on key findings and ideas in the animal literature, such as the “behavioural tagging theory” BTT; . BTT itsInterestingly, a tag is believed to last approximately 90 min , which mFinally, the interplay between PE, protein synthesis and consolidation is also captured in the phenomenon of reconsolidation, by which reactivated memory traces are destabilized and altered . This pr10While PIMMS can explain some of the situations where surprise improves declarative memory, and some situations where simple novelty does not (or even produces worse memory), it clearly has several limitations. Foremost, PIMMS is a framework for thinking about different types of novelty . The Gates Cambridge Trust funds JAQ’s PhD studentship. The authors declare no conflicting interests.Jörn Alexander Quent: Conceptualization, Visualization, Writing - original draft, Writing - review & editing. Richard N. Henson: Conceptualization, Visualization, Writing - original draft, Writing - review & editing. Andrea Greve: Conceptualization, Visualization, Writing - original draft, Writing - review & editing.