Background: Poor adherence to nicotine replacement therapy (NRT) is associated with low rates of smoking cessation. Hence, this study aims to identify and map patient-related factors associated with adherence to NRT using the capability, opportunity, motivation, and behaviour (COM-B) model. Methods: A systematic review was conducted by searching five databases  and grey literature on 30 August 2020. Data were extracted, thematically analysed, and mapped to the COM-B model. The Joanna Briggs Institute (JBI) critical appraisal tool was utilised to assess the quality of studies. Results: A total of 2929 citations were screened, and 26 articles with a total of 13,429 participants included. Thirty-one factors were identified and mapped to COM-B model: psychological capability , physical capability , reflective motivation (perception about NRT and quitting), automatic motivation , physical opportunity (cost), and social opportunity . The most prominent element associated with adherence was reflective motivation followed by physical capability and automatic motivation. Conclusions: Multiple personal, social, and environmental factors affect NRT adherence. Hence, it is recommended to implement a multifaceted behavioural intervention incorporating factors categorised under the COM-B model, which is the hub of the behaviour change wheel (BCW) to improve adherence and quitting. Tobacco smoking is one of the main public health concerns that the world has ever faced . Since tOne factor that has been shown to have a direct effect on the success of smoking cessation treatment is adherence to smoking cessation medications . A revieIn the behaviour change wheel (BCW), which is broadly utilised to design and implement successful behavioural change interventions, the capability, opportunity, motivation, and behaviour (COM-B) model is at the hub of the wheel. The COM-B model suggests that behaviour is the result of an interaction between three components: capability, opportunity, and motivation. These components are further divided into six subcomponents: psychological capability, physical capability, social opportunity, physical opportunity, automatic motivation, and reflective motivation . The comAmong the smoking cessation medications, NRT has the lowest half-life, especially nicotine gum and spray, with a maximum of two to three hours; whereas, the half-life of bupropion and varenicline is 22 and 24 h to ease adherence as compared to NRT ,22. MoreA detailed understanding of the barriers and facilitators of adherence to NRT is crucial for the development of comprehensive and effective interventions that can improve the success of smoking cessation. This systematic review aims to identify barriers and facilitators of adherence to NRT and to map the identified factors into the six sub-components of the COM-B model. As the COM-B model is the heart of the BCW, it will guide researchers and policymakers to develop targeted strategies that may improve adherence to NRT and smoking cessation . https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020186621 , Smoking cessation [MeSH Terms], cessation [all fields], smoke [all fields], cigarette [MeSH Terms], Quitting [all fields], Quitting Smoking [all fields]“Medication Adherence” [MeSH Terms], Adherence [all fields], Discontinuation [all fields], Compliance [all fields], “Medication compliance” [MeSH Terms], Non-compliance [all fields], Non-adherence [all fields], “Treatment Compliance” [all fields], “Therapeutic Compliance” [all fields] “Nicotine replacement therapy” [all fields], NRT [all fields], “Nicotine patch” [MeSH Terms], Patch [all fields], “Nicotine gum” [MeSH Terms], “Nicotine inhaler” [all fields], Inhaler [all fields], Lozenge [all fields], “Nicotine spray” [all fields], Pharmacotherapies [all fields], “Drug therapies” [all fields], “Pharmacological therapy” [all fields], and “Medication treatment” [all fields].Data extraction for quantitative studies was performed by two reviewers  independently for each article. Data extraction from qualitative studies were performed using Nvivo 12 software . Factors associated with adherence to NRT were identified, coded, and analysed using framework analysis. The data extraction template incorporated information on the identification of studies, methodological characteristics, and main findings regarding the barriers and facilitators of adherence to NRT. When there existed a disagreement between reviewers, it was resolved through discussion and mutual agreement.The quality of each study was assessed using the Joanna Briggs Institute (JBI) critical appraisal tool . StudiesData were extracted and analysed using a framework analysis and factors associated with adherence to NRT were mapped into the six sub-components of the COM-B Model  using a guideline set out by Michie and colleagues . Two revA total of 3278 citations were gathered through database and grey literature searching. After removing 349 duplicates, the search resulted in 2929 citations for screening. After a full-text screening of 103 studies, 26 articles were included in this review  with a total of 13,429 participants .The review included 26 studies, which included fourteen randomised controlled trials ,41,47,48All eligible articles were published in the English language. The majority of the included studies were conducted in the USA ,49,50,51Twenty-five studies were conducted among adult smokers and ex-smoker participants ,49,50,51The mean age of participants included in the review ranged from 16.6 years old  to 49.9 The COM-B model , and its sub-components were used to group factors associated with adherence to NRT among participants who smoke. This systematic review identified a total of 31 factors  associatThis theme explored the psychological capabilities of participants of the studies to adhere to NRT. Adherence to NRT was found to be associated with the level of education . CompletForgetfulness was a significant factor affecting participants’ adherence to taking NRT medication. A study conducted among adolescents in the Netherlands secondary school students reported forgetting to take NRT (38%) as one of the main reasons for non-adherence to NRT.  SimilarlOne of the interviewees said, “I’m currently couch surfing…I try to keep the box of patches [nicotine patches] in my suitcase but sometimes I forget.”Participants of the study also suggested putting the nicotine patch with other medications or their toothbrush and keeping it in a more visible place as a strategy to avoid forgetfulness .Another participant said, “I put it where, you know, like the deodorant and the perfumes and the colognes are, which is what I do in some of the medications that I take and they’re right here and I’m going to make sure that I put it on. But that’s how I remember things.”Moreover, participants who had a high level of confidence about quitting were found to adhere to NRT better than participants who did not have confidence in themselves ,48. HoweThis category assessed participants’ physical capability to adhere to NRT. The association between nicotine dependence and adherence is inconsistent, some studies show an inverse relation ,37,47, wFour of the studies included in this systematic review found a higher level of adherence among participants with strong nicotine dependence ,17,32,42On the contrary, three studies found an inverse relationship between stronger nicotine dependence and participants’ adherence to NRT ,37,47. IRelapse was usually associated with a higher level of nicotine dependence and shown to have an inverse relationship with adherence to NRT . RelapseThe number of years of smoking may be a factor to consider, as it might affect nicotine dependence. Similar to the level of dependence, there are controversies regarding the duration of smoking and its association with adherence to NRT ,41. For Participants who experienced greater levels of withdrawal symptoms had lower adherence to NRT ,47. StraNRT may have side effects such as skin irritation, hiccups, loss of appetite, nausea, unpleasant mouth taste, insomnia, irritability, sore throat, and increased blood pressure. Premature discontinuation of NRT due to experiencing side effects was another physical capability factor found to be associated with NRT adherence ,42,44,51One participant said, “Regardless of where I put it…my skin was still itching through the patch, so I’d scratch right on the patch.”In addition, the taste of oral NRT can be a factor for non-adherence, which is illustrated in a qualitative study.One consumer using oral NRT said, “Yeah, totally delayed cos I keep saying ‘oh I don’t want to taste it yet, I’ll give it another ten minutes you know, or I’ll give it a bit longer’. It is delaying it cos you think I’m not looking forward to the taste of it so I’ll just wait a bit longer.”In addition, among pregnant women, increased intensity of morning sickness was a deterrent to adherence to NRT. A pregnant woman said, “I was just more worried about the side effects obviously because I’m quite early on in pregnancy, and especially with morning sickness anyway, I didn’t know that it [NRT] would cause—obviously [it] made me feel more nauseous and [I] vomited quite a few times when I had the gum. So just would have been nice to have a heads up about it that it makes you feel sick”.Studies consistently reflected the direct relationship between the level of motivation to quit smoking and adherence to NRT ,43,44,48One participant said, “… I know it’s helping me out. I haven’t missed a dose because I’m motivated.”Motivation has two sub-components: Reflective motivation encompasses individuals’ conscious decision, plan, and evaluation of the problem and the NRT. Whereas, automatic motivation includes impulses, emotions, habits, and desire to see positive health or other outcomes The reflective motivation category includes factors that affect an individual’s evaluation of NRT and quitting, planning, and conscious decision-making processes. Adherence to NRT was found to be poor among participants who believed NRT has no effect in supporting one’s quit attempt. For example, in a study conducted in the Netherlands, more than one-third of adolescents believed NRT had no effect and discontinued the treatment prematurely . SimilarConcern about the safety of NRT was one of the main factors affecting participants’ reflective motivation to use the medication. Participants who believed NRT was not safe tended to discontinue the medication prematurely or utilised lower doses of NRT than the recommended dose . Thus, hOne person stated that, “Well, all they keep saying is you know it gets rid of the toxins, you still get the nicotine but it gets rid of the toxins, this, that and the other and it’s just in that the nicotine you take it in. The nicotine itself is what makes it addictive, so to me the more nicotine that you’re taking in any way, the more you’re going to want to smoke or you know you’re going to need that nicotine.”The perception of smokers and ex-smokers that following health care providers’ instructions was an easy task was associated with better adherence to NRT .When individuals failed in their attempt to quit smoking several times, it was associated with a decreased motivation for further attempts. It has been shown that the higher the number of previous quit attempts, the lower adherence to NRT and vice versa  16,34].,34.16,34This category includes factors that affect adherence to NRT by influencing an individual’s emotions, impulses, and unconscious associations with the performance of the desired behaviour, e.g., daily routines.In this automatic category, one of the main factors affecting adherence to NRT was found to be the mental health status of the individual. Participants who were not diagnosed with depression had more than double the level of adherence to NRT compared with participants who were diagnosed with depression  . SimilarIndividuals who were experiencing a higher level of stress had a lower level of adherence to NRT . HoweverAlcohol consumption was associated with an increased level of smoking. It was shown that individuals with alcohol dependence problems found adhering to NRT challenging .In addition to this, fearing dependence to NRT  and beinA participant said, “It’s a routine. I put it on after I shower in the morning and put the patches next to my medication.”Similarly, HIV-positive Latino participants in a qualitative study illustrated how they associated taking the NRT with their other medications .Another interviewee stated, “I leave it [the patches] next to my medication and remember to take it at the same time each day.”This subcomponent describes how the physical environment affects an individual’s level of adherence to NRT . The cosAlthough NRT is an over-the-counter product approved by the Food and Drug Administration (FDA) in the U.S., its price may be prohibitively high for most minors, thus discouraging effective use of NRT .It is suggested that factors such as gender and age have an association with adherence to NRT. Being a male and of older age was associated with better adherence to NRT ,33,35,49This component of the model consists of factors outside of the individual that makes the performance of the behaviour possible. Having a better social network and support affects adherence to NRT both directly and indirectly through influencing one’s motivation to quit smoking . A randoThis review identifies factors using a predefined behavioural model, the COM-B model, which is at the hub of the BCW that was effectively used to design and implement behavioural change strategies. Hence, the intervention functions and policy categories in the BCW are used to recommend and discussed the findings .Strategies that aimed at addressing intervention functions of the BCW such as enablement, education, and training were found to be effective in improving psychological capability of an individual towards adherence to smoking cessation medications ,55. For In this review, except for the level of nicotine dependence, all other factors mapped under physical capability were consistently associated with either high or low level of adherence to NRT. Studies that reported an inverse relationship between the level of dependence and adherence to NRT also reported relapse to smoking and dropout from the study, which may have contributed to the inverse relationship between the two variables . PrescriFurthermore, withdrawal symptoms were one of the most commonly reported causes for nonadherence in the category of physical capability. When attempting to quit smoking, experiencing greater levels of withdrawal symptoms could become a barrier to abstinence, which also applies to NRT aided smoking cessation . This exMedication-related beliefs and expectations were the main factors categorised under the reflective motivation subcomponent of the COM-B model. A randomised factorial study also found a significant positive effect of additional medication-related face-to-face counselling and automated phone calls directed to improve knowledge about NRT . EstabliMotivation improves once ability to cope up with withdrawal symptoms and improves the appropriate consumption of NRT . PsycholThe rate of adherence to NRT was improved among clinical trial participants for whom associating medication with regular activities such as taking other medications, with meals, and watching preferred TV shows were achieved with the help of therapists . Being aFactors categorised under opportunity component of the COM-B model can be improved by addressing the fiscal measures and legislation elements in the BCW that advocate access to NRT . AlthougOur search strategy was broad and comprehensive and was developed with the help of an experienced librarian. As only one study was conducted in a developing country, caution should be taken during interpreting the findings especially in developing countries; there were also some inconsistencies in the direction of the association between some factors. Moreover, the COM-B model did not distinguish intentional and unintentional nonadherence. Despite these limitations, this systematic review is the first to evaluate enablers and facilitators of adherence to NRT using the theoretical framework of the COM-B model.Health care providers are recommended to provide adequate information about withdrawal symptoms and NRT, address safety concerns, and establish realistic expectations. Individuals are recommended to boost their motivation and mental health by having social connections, physical activity, and managing stress. It is also recommended for patients to visit health care providers, smoking cessation support services, or access a Quitline for psychological support and counselling.Subsidisation of smoking cessation medications and care are advocated and recommended to improve adherence to NRT and the success of smoking cessation attempts. It is recommended to advocate policies and strategies that can enhance motivation to quit smoking through the promotion of the health benefits of smoking cessation and smoking cessation supports.Additionally, as the review illustrated the importance of factors at multiple levels, implementation and evaluations of trials addressing multiple components of the COM-B level are recommended.More studies, especially among special population groups, such as pregnant women, individuals with psychiatric disorders, and socially disadvantaged individuals, are recommended to develop more tailored approaches. In addition, as gender is an important factor for adherence and successful quitting, future research should include gender-based analysis.The current review demonstrated the importance of personal, social, and environmental factors affecting adherence to NRT using a comprehensive predefined theoretical framework (COM-B model). Most of the identified factors were mapped under the category of the reflective motivation component of the COM-B model followed by physical capability, and automatic motivation. Hence, reflective motivation is the most crucial element for adherence to NRT out of the six sub-components of the COM-B model. However, it should be noted that all sub-components of the COM-B model are essential in moderating an individual’s behaviour concerning adherence to NRT. For instance, motivation cannot provide opportunity, and if these are missing, then according to the COM-B model, behaviours have to be engaged with to increase or seek out opportunities, which may be beyond an individual’s control.


Quality and respect are increasingly recognized as critical aspects of the provision of health care, and poor quality may be an essential driver of low health care utilization, especially for maternal and neonatal care. Beyond differential access to care, unequal levels of quality exacerbate inequity, and those who need services most, including displaced, migrant, and conflict-affected populations, may be receiving poorer quality care, or may be deterred from seeking care at all.Examples from around the world show that mothers and their children are often judged and mistreated for presenting to facilities without clean or “modern” clothing, without soap or clean sheets to use in the hospital, or without gifts like sweets or candies for providers. Underfunded facilities may rely on income from those seeking care, but denying and shaming the poor further discriminates against vulnerable women and newborns, by placing additional financial burden on those already marginalized.The culture of care needs to shift to create welcoming environments for all care-seekers, regardless of socio-economic status. No one should fear mistreatment, denial of services, or detainment due to lack of gifts or payments. There is an urgent need to ensure that health care centers are safe, friendly, respectful, and hospitable spaces for women, their newborns, and their families. Ambitious global goals, such as the Sustainable Development Goals (SDGs), require health to be viewed as holistic and inclusive. Beyond clinical care, attention must be paid to quality, responsiveness, and patient-centeredness. The Lancet Global Health Commission on High Quality Health Systems found that more deaths globally could be attributed to poor quality than access, and care without quality has been called an “empty promise” , 2. AlthPoor quality care exacerbates inequity: the most vulnerable may be subject to the most disrespectful or inadequate care, which can lead to avoidance or delays in seeking care for those who need it most. Marginalized women and their families, including those who are in geographically isolated and conflict- or disaster-affected areas, may decide that the benefit of receiving sub-standard care is not worth the cost of seeking it. For those who do seek care, many do not reap the full benefit due to lack of full understanding, consent, or participation, including not providing full information to providers for fear of condescension on denial of care , 10. TheAlthough lack of respectful, dignified care is a worldwide issue , those wHow can improving quality of care and client experiences be used as an ‘accelerant’ instead of a deterrent to care-seeking? While health care workers and policymakers often attribute low facility utilization to “traditions” and “culture,” women themselves often place primacy on the perceived quality of care and will overcome barriers of gender inequity, decision-making power, cultural norms, transport, and geography to access what they perceive as high-quality care .While the level of complexity and need for significant investment may stultify efforts to enact immediate change, starting at the facility door may be a crucial first step. Care-seekers perceive the culture of a health facility, and the expectations on how one must present may be insurmountable for many . Care-se“However, in the hospital they want us to buy diapers, socks, and blankets so the newborns are all the same… If a woman does not want to buy clothes for her child they say, ‘Well, then you should be operated on so you don’t have any more children since you do not have enough money to take care of your children.’ For this reason I did not want to go to the facility.” –Interview, woman, rural Guatemala [uatemala “She [the nurse] told me, ‘You didn’t bring clothes for your baby? Do you not care about your child? How can you be a parent if you cannot clothe your baby.’” –Focus group, women, rural Zambia [l Zambia For women and families who come to facilities without required items, new evidence suggests they may even be illegally detained, along with those unable to directly pay for services, contributing to the alarming and underreported phenomenon of imprisonment in health facilities :“If you deliver in the hospital you have to pay for sweets and soaps which some people cannot afford and so they prefer to deliver from home. If you deliver in the hospital and do not pay for sweets and soaps, you will not be discharged; this needs to be stopped.” –Focus group, women, South Sudan [th Sudan Demands for payments may be a way for the facility to raise needed funds for operating costs, and to fill health systems gaps; demands for new clothing may be an opportunity to exploit those needing care, and imposing “disciplinary” measures may be functions of providers’ implicit attempts to advance “modernization” of their communities . HoweverTo start closing the equity gap and promote better health outcomes, facilities must stop requesting or insinuating the need to provide unnecessary items and must be funded to sufficient levels so as not to rely on payments and equipment provision by those seeking care. Where fees are still in place, costs must be transparent, waivers must be available, and those unable to pay or bring in-kind goods should never be penalized, scolded, or detained. Although larger system changes are needed to improve the working conditions of facility staff so they can provide better care, some programs that focus on provider reflection and acknowledgement of implicit bias and marginalizing practices, such as values clarification and attitude transformation exercises, have shown impact on improving respectful interactions between those needing and providing care , 19. Becculture of care for women and newborns – it will continue to cost lives and dignity if we do not act.A system which provides poor treatment for poor women strips individuals and families of their basic right to health care. The new study from Bayo et al  joins a


Physician Career Choice and Satisfaction: Empirical Studies of Practicing Physicians summarizes the results of three studies that detail how and why physicians choose the types of practices where they work, physicians' personal characteristics, and their satisfaction with their work. The author of the book's preface, John R. Graham, notes that the University of New Mexico's medical school was established in 1961 and that there was debate among its teaching faculty on how to best teach medicine (p. iv). He adds that people learn best when they have a reason to learn rather than learning and regurgitating facts, as research from George Miller at the time showed. Therefore, the “shift toward motivation for learning emerged” (p. iv).Gerald Otis's initial data collection about physicians' career choice and satisfaction began in 1968 and captured information on the medical school's first graduating class (p. iv). Otis's research was born out of concern about the “apparent development of increasingly cynical attitudes of medical students…during” medical school (p. 10–11). The research also includes a study of practicing physicians and a study of medical students doing summer externships. Data collection ended in the mid-1980s due to funding issues, but Otis resumed it later (p. 7).The research looked at data about medical students and followed up with them as physicians years later. The data include the distribution of physicians across the various medical specialties, personality types, geography, income, level of patient contact, test scores, grades, and types of practice. Otis notes that certain types of characteristics—such as the kind of community the physician grew up in, family size growing up, or personality characteristics—may lead a physician to certain medical specialties (p. 53–61).However, in the 1960s, the Student American Medical Association members believed that low recruitment to primary care was due to a specialized approach to patients in medical school and a lack of exposure to primary care (p. 135). Thus, the Medical Education and Community Orientation Program (MECO) was proposed in 1969 to allow preclinical students to get primary care experience through short rotations of up to ten weeks in community settings (p. 135). In addition, participation in summer externship programs, where students are placed with a physician preceptor, can significantly affect students' “medical attitudes and career dispositions”; however, Otis adds that success depends on both “program characteristics and student characteristics” (p. 156).Otis notes that a general assumption in the longitudinal study is that the degree of satisfaction with a career choice depends on the degree that personal preferences align with aspects of a career that satisfies those preferences (p. 13). For example, various types of practices, such as partnerships or solo practices, differ from one another as well as the characteristics of physicians who do well in them, which can influence physicians' satisfaction, or lack thereof, with their work.Quenk refers to the need to increase the desirability of working in Veterans Affairs (VA) hospitals, which are unattractive for a number of reasons, including low income; however, there are other issues at play, including administrative factors, so Quenk thinks it is unlikely that higher pay would make a difference (p. 122–123). Quenk adds that data show there is sometimes variation in satisfaction from one specialty area to another (p. 122). Otis suggests that a consortium or alliance of medical schools should work together to continuously research the area of physician career choice and satisfaction (p. 157).The text is readable but would likely not interest readers outside the medical field, as it contains material that some readers would find difficult to slog through. This reviewer believes the book's intended audience is teaching faculty or administrators at medical schools who need to select students who are likely to be successful in medical school and be satisfied with their career choices. In addition, it may be useful to medical school students who are uncertain about what type of specialty or practice to select as well as those who are interested in attending medical school. The text does have some errors, such as inconsistent type size, line and word spacing errors, occasional spelling errors, and inconsistent paragraph justification. However, that does not outweigh the value of the information to faculty and administrators in medical education, as well as potential medical students. Therefore, including it in an academic library collection that supports potential medical school students is also a possibility. Therefore, this reviewer recommends this book, but only in these contexts.


Rosenberg’s dramaturgy, as it appears in these texts, serves less as a target of criticism than as an exemplar of a narrative arc.“An epidemic has a dramaturgic form,” wrote 4 It offers, in its “drift towards closure,” “an identification of an epidemic’s end as the point when the urgency of the disease outbreak has sufficiently diminished.”5 As such it becomes a foil to other possible endings, for different people at different times. “Not only does a given epidemic ‘end’ at different times in different locations, and for different groups in the same location,” Erica Charters and Kristin Heitman remind us, “but also for different academic disciplines: epidemiologists, anthropologists, policymakers, and historians follow different parameters to gauge the decline and end of epidemics.”6 By raising different possible endings, these historians foreground the people and organizations who decide on the end of an epidemic, as it occurs and after, and those excluded from this decision-making.Adapting Mary S. Morgan’s description of narrative, Rosenberg’s “dramaturgy” “create[s] a productive order amongst materials with the purpose to answer why and how questions.”In the extended public engagement with epidemiological science during the COVID-19 pandemic, these interventions have particular political, social, and ethical urgency. They help to explain why different stakeholders might experience different feelings of resolution or irresolution. But resolution depends more on closure, the term Rosenberg uses, than on ending, which is favoured by his respondents. Interpretations of endings, made by policy-makers, populations, and public health experts in the moment, and by historians after the fact, must often balance a desire for closure against those facts that disrupt it. The aim of this essay is to bring the relation between closure and ending to the fore, and so offer a conceptual tool for historians to explain why some endings bring resolution and others do not. In what follows, I first clarify what I mean by ending and closure. Then I rehearse some of the arguments used by historians engaging with Rosenberg and critical epidemic endings, to show how their engagements with the writing of epidemic history might benefit from a more explicit distinction between ending and closure. Raising this distinction is not simply a problem of terminology. It has consequences for both historical research and the writing of historical narrative. Accordingly, I consider how narrativist and post-narrativist approaches to the philosophy of history have responded to the problem of closure.Poetics, “is that which itself naturally occurs, whether necessarily or usually, after a preceding event, but need not be followed by anything else.”7 It is the moment when things stop. Closure, as Tobias Klauk et al. have argued, describes a “feeling of finality,” an “impression that the story is complete,” leaving “no further questions” concerning its content.8 Rather than the moment when things stop, it describes a formal resolution, wherein one feels one’s questions have been answered and one’s expectations satisfied.“An end,” writes Aristotle in the As a provisional definition, I want to suggest that endings in epidemic histories present interpretative acts of terminus. These acts are made by authorities, underwritten by collective agreement, and shaped by external conditions. But they also operate through the decisions of working historians, who, through heuristics, critique, and interpretation, establish contingent end points for historical periods. I emphasize “interpretation” and “decision” because, insofar as critical accounts of epidemic endings problematize these endings as given, they implicitly depend upon rival interpretations of what facts or testimonies are materially relevant, and upon the historical actors deciding on these matters.9 Does the narrative (or the circumstance) satisfy our expectations of what such an end might look like, and does it answer many, most, or all the outstanding questions that we might have? Insofar as an ending may satisfy our expectations without necessarily resolving all our questions (or vice versa), it may have an end without (complete) closure. Or, a condition may satisfy our expectations and answer our questions without ending. In such a case, we can say this is a closure without end.Closure, however imbricated in this understanding of ending, remains distinct from it, since it describes the degree of resolution these endings bring. When the participants in the historical moment experience this resolution, we call it psychological closure, and when it occurs in a historical narrative, we call it narrative closure. In both cases, this resolution can be broken down into the fulfilment of expectations and the answering of questions.This difference means there can be endings without closure and closure without endings. A disease might be eradicated, while leaving no firm feeling of finality for those who continue to bear its scars. Here, we might identify an ending without any ready experience of closure. Conversely, when a disease, once epidemic, begins to be accepted as endemic by policy-makers, populations, and public health experts, this acceptance gives the impression that the epidemic is complete without the disease ever really stopping its spread. In this example, closure happens without any discernible ending. But cases are rarely so clear cut.10 Although the epidemic has ended, the closure each actor experiences differs. The epidemiologist or public health official announces the success of the programme, an act that becomes synonymous with the end of the epidemic. Supported by research findings and avowals of professional judgement, this announcement presents an explanatory resolution of the crisis that produces narrative closure. But the officials may have some doubts about the programme’s efficacy. This lingering uneasiness translates into a lack of psychological closure for the officials, if not for the public that believes in them. If such doubts are articulated, and these articulations become public knowledge, this lack of psychological closure may call into question the story’s narrative closure. Likewise, those people left scarred by the program’s effects may not feel their expectations satisfied or questions answered, even if they accept that support for the crisis has ended. Conversely, they may be all too ready to announce the end, perhaps even before the information concurs with such an assessment. Here, psychological closure can advance declarations of an end, outflanking the best intentions of those epidemiologists presumed to know.Imagine, in the wake of a devastating epidemic, a successful eradication programme leaves the living to bury their dead, uncertain of what happened and dissatisfied with whatever actions were taken, but, on the whole, relieved the epidemic is “over.”The historian, coming after, might draw on the epidemiologist’s notes to concur with their judgement, only to find a disparity between their public support for an ending premised on narrative closure and a private record of doubt and scepticism more closely aligned with those who feel left behind. In writing about epidemics, historians may agree with the public declarations, especially when made by organizations like the WHO, or epidemiologists or political leaders: in such cases, the declared ending maps closely to the narrative closure of the historical text. They can problematize these public declarations by revealing their authors’ private reservations, expressed in diaries or letters: although the story of the event retains its narrative closure, the historical text distances itself from that story by recalling a relative lack of psychological closure for actors at the time. Or, as in the case of the critical reflections of epidemics’ ending, the relative artificiality of such declarations presents a target for historical revisionism, whereby new questions may be raised and expectations frustrated: the linear narrative defining an epidemic’s rise and fall, once treated as closed, is wrenched open once more.11 In the context of COVID-19, Jeremy A. Greene and Vargha have observed that epidemics “have two faces.” These faces, “the biological and the social, are closely intertwined, but they are not the same. The biological epidemic can shut down daily life by sickening and killing people, but the social epidemic also shuts down daily life by overturning basic premises of sociality, economics, governance, discourse, interaction.”12 Inspired by efforts to find some organizing structure for the pandemic in Rosenberg’s dramaturgy, an entire special issue of Bulletin of History of Medicine re-examined his essay in light of the COVID-19 pandemic.13 And, while scholars dissected its blindness to conditions outside its North American context and its overly schematic reliance on a culturally specific dramaturgical sequence, these criticisms were offered, for the most part, as supplementary efforts to expand the model, rather than jettisoning it entirely.14 Charters and Heitman also outlined two possible endings for epidemics: biological eradication and a cultural acceptance that effectively normalizes conditions as “endemic.”15 As Greene and Vargha put it, endings that occur through cultural consensus tend to be asymptotic, where the graphic representation of actual cases is concerned: “rarely disappearing, but rather fading to the point where signal is lost in the noise of the new normal—and even allowed to be forgotten.”16Although Rosenberg uses the term “closure,” critical accounts of his essay have tended to interpret this as “ending,” which they go on to complicate in productive ways. Writing in 2016, Dora Vargha summarizes the defining questions for the study of epidemic endings, as “when and for whom diseases end, what happens when the end fails to come, who gets to determine the end and who gets left behind, how a focus on endings shape health policies and how we can critically rethink the temporalities of epidemics.”17 The endings, subsequently enumerated, are based on concrete historical examples.When it comes to endings, these different approaches tend to challenge Rosenberg’s model by offering exemplary cases that complicate its neat linearity. These examples pull together a combination of physical constraints  and collective consensus . As I have given them, the categories blur into each other, but this concerns me less than what is not given: a purely formal definition on what an ending is. When Vargha and Greene aim to “reconsider what we mean by the talk of ‘ending’ epidemics,” and subsequently propose to “take a step back and reflect in detail on what we mean by ending in the first place,” it is telling that this meaning is made through the “many forms” that “the history of epidemic endings has taken.”18 In using Rosenberg, the essays each assume a conventional understanding of ending that they go on to challenge. When the writers examine epidemic endings, they leave ending as a concept largely untouched. Or, to put it another way, by relying on a typology of endings to demonstrate how epidemics are framed “within cycles of disease and with a multiplicity of endings,” these accounts of epidemic endings do not really address the notion of ending that they seek to displace.19 This is why I believe a formal distinction between ending and closure helps to elucidate what remains implied in the case literature.Although such “thinking through cases” is, of course, useful, it leaves unstated what is meant by ending as such.20 This opposition exemplifies a common criticism of Rosenberg: he occludes variable endings and geo-cultural disparities. But it also highlights the equally common tendency to conflate closure and ending. This is a conflation because “ending” in these accounts does not simply describe definite external measures of terminus; it includes the feelings of satisfaction and completion that accompany these measures. When Lachenal and Thomas qualify the “endless” periods of epidemics as “seemingly,” they imply that it appears this way to a someone, whose dissatisfaction is conditioned by a period’s failure to fulfil expectations or answer questions. In this regard, endlessness is an impression that stems less from the lack of an ending than from a lack of closure.The only substantive reference to closure, across this emerging literature, appears in Guillaume Lachenal and Gaetan Thomas’s examination of dramaturgic form, wherein the “endlessness” of actual epidemics is opposed to the apparent panacea of their closure: “Instead of events oriented toward their own closure, epidemics might be approached as unsettling, seemingly endless, periods during which life has to be recomposed.”lack of closure.” This process of deferring closure, also known as suspense, is often a desirable feature in narratives, as is its counterpart, the upsetting of expectations, or surprise. “All successful narratives of any length are chains of suspense and surprise that keep us in a fluctuating state of impatience, wonderment, and partial gratification.”21 Many, in their direct experiences of “historical time” during the COVID-19 pandemic, may find this lack of closure less pleasing than, say, the deferred closure that future histories of this period will undoubtedly use. In one possible interpretation, then, closure would appear to be far more relevant for the writing, or “representation,” of the epidemic, than for the heuristics, critique, and interpretation at work in the methodical analysis of its unfolding. In his classical philosophy of history, J. G. Droysen suggests just such a distinction between writing and method, the better to establish the historian’s analysis as separate, and separable, from their techniques of representation, or style.22 For this reason, we might conclude that Rosenberg’s critics are right when they implicitly suspend closure from their examination of actual historical events: the material differences lie in the way people construe endings, and so endings serve as a more important topic of inquiry.Now, as H. Porter Abbott has argued, narrative is marked “almost everywhere by its 23 “Narrative,” as Morgan puts it, “is how the relationships amongst their materials become known to them.”24 Indeed, Charters and Heitman insist that, 25Focusing on how epidemics end is not simply a conceptual exercise, a narrative trick in which one views disease from a new perspective. Instead, it reveals the social and political processes by which a disease becomes endemic—that is, accepted—as well as who participates in that process and who is excluded.What this conclusion ignores, however, is the extent to which criticisms of Rosenberg’s model rely on the shaping force of the narrative model itself, whether through comparisons between the dramatic arc and William Farr’s epidemic peak, the replacement of Rosenberg’s Grecian dramaturgy with one based on other dramatic forms, or the recognition that, in some places, epidemics are experienced as periodic cycles with no final terminus.In making this claim, they imply that the narrative model plays a critical role in the interpretative act. But, by linking the endemic to “acceptance,” they are also implying, however obliquely, that these material processes set up expectations that can be satisfied or frustrated. So, even if we appear only to be talking about endings, these endings are still being mediated by different forms of closure.This raises the question of whether my distinction between closure and ending really needs to be developed in such elaborate terms. Surely, my argument might be better conveyed in 280 characters (or less), and to greater effect. “Great work on endings, but shall we unpick the ways these different examples grant or withhold closure?” To explain why it does, we might begin by bringing this work into closer alignment with the narrativist and post-narrativist approaches to the philosophy of history that arose in the wake of 26 To reframe White’s larger project in simple, even reductivist, terms, narrative fails to respect the distinction, marked in the scientific method, between the representation of history, through writing or other forms of presentation, and its interpretation. Narrative intrudes on interpretation, orienting it towards “fulfilment” (or closure). By proposing forms of history-writing that resist endings, the historians discussed above often gesture suggestively towards avoiding narrative closure: offering multiple, alternative ways of construing the end, recalling those for whom no simple end can be viable, and challenging the dominant narratives, usually determined by persons or organizations in positions of power and privilege, that propose clear and definitive endings. At first glance, we might imagine that White would find this self-aware engagement with the constraints of narrative all to the good. As Maria Grever writes, in a review of Kalle Pihlainen’s The Work of History (2017): “White particularly warned that the realist closure tends to domesticate and normalize the presentation of past events. The absence of closure reveals a narrative’s constructive and ideological nature, but it also provides room for reflection and discussion.”27 And, as Pihlainen, whose work offers some of the fullest engagement on White and closure, wrote almost 20 years ago, “closure causes discomfort”: “aesthetic closure causes discomfort because it is so clearly an imposition on the epistemological … moral closure causes discomfort because it is an evaluation of the other, and therefore a refusal to fully recognize [their] subjectivity.”28 The aesthetic form that Pilhainen describes, wherein closure restricts the epistemological possibilities of history, bears little resemblance to Abbott’s more technical description of satisfying expectations and answering questions. Doubtless this comes from the disciplinary differences: Abbott is concerned with a description of fictional narrative, whereas White and his followers make normative claims about historical narrative. But it might also explain how a seemingly technical matter of style can carry significant ideological baggage.In 29 A more expansive understanding, Espinosa argues, would explain how such events frequently play out on a regional or even global stage: after all, she wonders, why group the US with Western Europe over its more immediate Latin American neighbours? In identifying problems with Rosenberg’s “mode of explanation” and his “plot structure,” Espinosa gestures to a philosophy of history that, as White writes in Metahistory, “would appear only in the mode of explanation actually used to account for ‘what happened’ in the historical field and in the plot structure used to transform the story actually told in the narrative into a story of a particular kind.”30 Philosophies of history are implicit in the modes of explanation practicing historians use, not least in the ways they end up reproducing existing genres of scholarship when transforming the actual sequence of events into a historical narrative. That the historians are quite capable of addressing this transformation themselves, and in sophisticated terms, signals how scholarship has changed since White’s attack on vulgar realism. But it also confirms Carolyn J. Dean’s suspicion that, insofar as his legacy can be measured in mainstream history, it has “recast White’s attention to the language of representation as a form of critical self-awareness.”31 In offering their supplemental accounts as if they were “the story actually told,” replacing Rosenberg’s “story of a particular kind,” the historians signal that there is still more to be done to reconcile the practice of history with its philosophy.32 Or, in Dean’s analysis, “an openness to the diversity of argument may obscure other forms of methodological and professional consensus.”33The attention to alternative endings betrays a certain anxious antipathy, not merely to “closure” as a narrative term, but to an ideological completeness inferred in reading Rosenberg’s model. Focused as it is on the United States during the AIDS epidemic, Rosenberg’s essay defends the epidemic as a local event and relies on oppositions between the developing and developed world that have, as Mariola Espinosa demonstrates, “little value.”a narrative model might be useful. But, even as the literature affirms the interpretative value of narrative, it continues to depend upon concrete case examples, developed through archival research, to overrule narrative’s perlocutionary power. As such, it conditions the model with appeals to historical reality. The implicit post-narrativist sensibility at work here is not the thesis-driven philosophy history proposed by Jouni-Matti Kuukkanen.34 Rather, it resembles the post-narrativist framework proposed by Harry Jansen, where narrative and representation play a crucial role in understanding and interpreting historical events, while relying on distinct appeals to research and experiences of time.35 By defining endings through case examples, rather than a contingent definition, the historians repeat Louis O. Mink’s narrativist rule that the historical thesis is non-detachable: “What exemplifies [aspects of the past referred to in the narrative] and what is exemplified [the historical thesis] mutually depends on each other. Therefore, there is no such thing as a general historical thesis which is exemplified in different narratives.”36 At the same time, in the efforts to displace Rosenberg’s model, where it is too linear, schematic, or reliant on a single arc of expansion and contraction, the appeal is not, or not only, to alternative narratives.37 It relies on colligations that extend the epidemic beyond the strictures of the model.Within the emerging literature on epidemic endings, one site of implicit consensus appears to be that 38 When colligation plays a role in narrative ordering, or “configuration,” it assembles things “together under a label,” as an exemplary case.39 In the end of epidemics literature, these colligations allow the process of the epidemic—its affiliate events—to extend beyond what seems to be a conventional ending. As Morgan has argued, colligations do not create explanatory narratives, in and of themselves; rather, historians juxtapose several such colligates, in their essays, to prompt questions and offer answers.40 Since the epidemic’s discontents continue to arise after its end, the historians argue, these subsequent events, uncovered by further research, must be colligated into its process.According to W. H. Walsh, when historians formulate “inner connections between certain historical events” into “a single process, a whole of which they are all parts and in which they belong together in a specially intimate way,” this process, and its attendant rhetorical claims, is called colligation.41 What Jansen signals are subtle inclinations towards narrative and psychological closure during historical research that ultimately influence the writing of history. Regarding colligations, we might emphasise the rhetorical role played by encapsulated histories of previous pandemics in the emerging literature. Paragraph-length accounts of 1918 influenza, typhoid, smallpox, or polio produce all the values of a bite-sized colligation, while their enumeration emphasizes the multiplicity of endings at work. So, while the juxtaposition of case examples, in the form of colligations of other epidemics, keeps the possible epidemic endings open, the colligations themselves represent each of those epidemics as having achieved a certain degree of narrative closure. For this reason, the writing of history often depends on a research phase punctuated by prior moments of narrative closure, even when it tends towards openness. A parallel argument may be made for the psychological closure that attaches to perceptions of epidemic time as “discontinuous” from normal, “continuous” time, which “resumes” once the epidemic is over. Recalling how forms of narrative and psychological closure may be influencing the “sense of an ending” that attaches to an epidemic, not simply in its writing but across the research period, may further support the study of epidemic endings.But, as Jansen argues, this appeal to research relies on an argumentative infrastructure that unfurls in the preparation phase and acts as a “hidden persuader” during the writing phase. This argumentative infrastructure develops because of “the epistemic values of colligation ” and “the perception of a continuous or a discontinuous time.”My aim in this essay has been to extend discussions about epidemic endings by recalling the distinction between closure and ending. This distinction is generative, insofar as it prompts us to consider how the act of interpreting an ending may leave questions unanswered and expectations unfulfilled. To the questions already posed, about who decides an end and who is excluded from that decision, it adds: does the ending provide psychological and/or narrative closure to the participants, be they survivors, public health or political officials, or organizations, and how should these forms of closure be relayed by historians coming after? Dealing with these questions raises further questions for the writing of history: whether, when the historian relays a lack of closure in their materials, they develop a style that mimics this lack or bounds its description in more readerly narratives. What I have hopefully made clear is that such questions are not simply applicable for the larger narrative ordering of the book, monograph, or article; it permeates down to the paragraph-length case, a site where explanatory closure may deny the very openness implicit in asking how epidemics end.


Assembling Life, on the origin of life. It is unapologetically polemic, presenting Deamer’s view that life originated in fresh water hydrothermal fields on volcanic islands on early Earth, arguing that this provided a unique environment not just for organic chemistry but for the self-assembling structure that drive that chemistry and form the basis of structure in life. It is worth reading, it is an advance in the field, but is it convincing? I argue that the Origin of Life field as a whole is unconvincing, generating results in Toy Domains that cannot be scaled to any real world scenario. I suggest that, by analogy with the history of artificial intelligence and solar astronomy, we need much more scale, and fundamentally new ideas, to take the field forward.David Deamer has written another book,  Assembling Life—hereafter AL) [First Life—hereafter FL) covered the ground extremely well [David Deamer has written another book on the origin of life (fter AL) , and it ely well . AL is mTo signal my intentions from the start, yes, I think you should read both books. FL is fun, a cracking read, detailed and thorough. It is also full of David’s trademark personal asides and comments, especially on the origin of the words and hence on their semantic baggage. AL also has trademark Deamer touches, as well as great introductions to background concepts. So read both, because Deamer has done a good job of laying out all the more mainstream options, and developing his thesis that life probably originated in fresh water hydrothermal systems from self-organizing fatty acid lamellae. I find the argument compelling to the extent that it fills in some of the gaps.Deamer’s view might be summarised as “container-enabled chemistry first”. Long chain fatty acids can be made abiotically, and spontaneously assemble into multilayer structures on drying from freshwater hydrothermal fields, structures that break up again into vesicles on wetting. Why fresh water hydrothermal systems? Because in seawater divalent cations, especially calcium, prevent fatty acids from forming bilayers, as well as efficiently precipitating phosphate and organophosphate compounds . Other then macromolecules, then chemistry. His view is that there are a range of sources of organics in all scenarios of prebiotic Earth, and the problem to be solved is how they organize, both through self-assembly and polymerization. After some good introductions to what we know (very little), can reliably model (some) and conjecture (a lot) about the early Earth, he gets down to business in Chapter 4, all of which is devoted to potential sources of organics. Some sources  are hard to reconcile with a hydrothermal field environment, but we pass on. Chapter 5 is boldly titled “Self-assembly processes were essential for life’s origins”, and this is the core of his thesis. Not only does self-assembly create physical structures, it creates chemical environments that can enable early synthesis. Some of this is over-stated. Yes, DNA will spontaneously form double helices, but only if incubated at the appropriate temperature in the right ions, and you need to incubate for days to get half a bacterial genome to re-associate even at mg/mL concentrations [But the importance of this environment for Deamer lies not just in the chemical reactions it enables. Rather, it is its ability to enable self-assembly, which he considers primary and fundamental. Hence the title of the book, and the order of the chapters—Self-assembly, trations ,7), and trations . This soif a few accumulate random polymers and if those random polymers contribute to the vesicle’s stability, then the polymers and their lipid components are preserved. (They are not “replicated” because there is no information transfer). This sort of random combinatorics could select a combination of properties through cycling through vesicle, gel and lamella phases of the fatty acids, a process Damer and Deamer call “coupled phases” [Deamer has at least part of the solution to how functional, or at least stable, polymers could be found among the vast majority of non-functional ones (putting side for a moment what we mean by “function”). Cycling fatty acids between dehydrated and hydrated states in fresh water allows for the generation of a huge population of self-organizing vesicles, each of which will be slightly different. Dehydration also drives condensation reactions. Of billions of vesicles formed,  phases” . So the shows that fatty acids spontaneously form multilammellar structures on drying, in lab and in actual hydrothermal water samples. He has demonstrated this with organics extracted from the Murchison meteorite, so this works with real abiotic samples, not just lab chemicals. He shows that lamella formation drives the formation of something like RNA from nucleoside phosphates, a specific example of the hypothesised synthesis and subsequent kinetic trapping of dehydration polymers by wet/dry cycles working on monomers trapped between lipid layers, and that these are retained inside smaller, vesicle-like structure when the lamellae are wetted again. He has gone to actual, real hydrothermal ponds and dropped chemicals into them to see what will happen, pools as extreme as pH = 0 vent water, and shown dehydration polymerization under pool conditions [Unusually, Deamer devotes all of Chapter 9 to actual lab results. For example, he actually nditions . This issome of which happen to encode genetic information in the linear sequence of their monomers while other catalyse polymerization reactions” . The chapter then goes through the steps, the evidence, and future tests. This has been expanded in [Chapter 10, co-authored with Deamer’s collaborator Bruce Damer, then pulls all the arguments together. It starts with a bold statement: “This chapter proposes that life can begin with chance ensembles of encapsulated polymers, anded in ,11, and Deamer suggests that the next step is to go beyond one-at-a-time chemistry and try a wider range of chemistries, almost a Miller–Urey-type experiment but looking for structure, not chemistry. His Figure 8.1 (AL) shows his system for doing this in 24 combinations of environments at once. In this, he is aligned with Smith and Morowitz’ comment that “Rather than seeking the emergence of a novel and unified form of order from the beginning … we seek the dispersed opportunities for chemical and physical order provided by the Earth’s chemistry and dynamics, and ask how they were brought into interdependence and thus granted partial autonomy from non-living geospheres” . Deamer’But. Here is the fundamental problem. There is only one actual fact known about the origin of life (OOL). It happened. We do not know where, when, or how. Suggestions on location range over clouds ,14,15, iAnd as to the path to life, we have as many theories as there are molecular types in a cell. Deamer assumes that the organic chemicals that make the necessary structures come from an abiotic environment. But this is an assumption which the hydrothermal vent school disputes. And from that first abiotic chemistry we get metabolism first, genetics first, container first, iron-sulfur world, small molecule world, protein world, lipid world, carbohydrate world and of course RNA world.fresh water in part because it uniquely enables self-assembly of fatty acids. But Black and co-workers have found that amino acids can bind to fatty acids  and allow them to form bilayers in the presence of divalent cations [Choose your key properties for life, your preferred path, find a location that matches those, and you have a new scenario for life, and one that can match your preferred mechanism better than any other. But it is not an objective choice. For example, Deamer’s choses  cations ,33, i.e.And so I nearly put AL down at first glance. In the introduction Deamer contrasts two options—the now-classic cool alkaline serpentinizing seafloor origin and his preferred volcanic hydrothermal field origin—from a list that encompasses dozens if not hundreds. Maybe I am unduly obstreperous, but I felt myself thinking “No, hang on, what about …” before I had got beyond the preface. Which would have been a mistake.But Deamer makes a more basic, and unstated, assumption, as does most other OOL literature. OOL scenarios usually assume that life occurred in an environment that was fairly predictable, not some fantastic chance occurrence. That itself is not proven. The Principle of Mediocrity  does not apply. If life was a fantastically unlikely, once-in-a-Universe occurrence, we would of necessity be living on the only planet in the entire cosmos that has life; we have to be, because we are alive This is why I found the experiments posited in Chapter 10 slightly unsatisfying. Despite the quote, Deamer is not trying to solve the problem of how translation appeared. He is looking solely at the earlier step of how to assemble big molecules in water. But, to paraphrase the song, there must be fifty ways to lose some water. Dehydration in lamellae is one way, and has advantages over dry dehydration which Deamer discusses, but many other solutions have been postulated for overcoming “the water problem” ; the prois a wet-dry cycle, does this mean, as Lineweaver has argued [But there is an even bigger problem. We do not even know what life is. We know that we are alive, but we know that we are alive because we define life as what we are. Everything else is conjecture. Many authors have argued that trying formally to define life is both philosophically futile and practically pointless , ands argued , that huThis is not pointless sophistry. There is a reason to be more specific in characterizing life (let us not say “defining”), the need for precision in language. Along with most other writers on OOL, Deamer uses “evolve” to mean “change” and to mean “the result of selection for fitter genotypes”, with the implication that one is related to the other. This is seriously misleading. Similarly “replication” can mean production of a new organism from a genetic blueprint (as in “viruses replicate”) or kinetically-determined self-catalysis . In my  book these are fundamentally different processes; using common language implies they are not, but does not elucidate their similarities or differences. Again, the term ‘Protocell’ is used to mean any liposome-like membrane encapsulating other molecules. In my opinion, a vesicle encapsulating random organic molecules is almost as far from life as the bulk “prebiotic soup” from which it was made. To draw “Protocells → Progenote” in a diagram  skips ovDamer and Deamer, in AL and elsewhere  imply tBut studies of the origin of life are not unique in not being able to define or precisely describe their subject matter. Psychiatrists cannot define what mental illness is except as a list of symptoms that we hope we do not have. Researchers in artificial intelligence (AI) cannot agree what intelligence is, except to define it as what we  have. And yet psychiatry and AI flourish. Why should OOL not do the same?Because, I suggest, OOL is at least 50 years too early. OOL in 2020 is like AI in 1950. It was missing several critical pieces. We are playing with Toy Domains .2001: A Space Odyssey could be outwitted by its human crew. Programs were demonstrated that could plan, talk, play games, even diagnose medical conditions [After WW-II, there was a huge burst of enthusiasm for computers and their abilities. Science Fiction, popular media and technical researchers alike believed that we were on the brink of generating genuinely intelligent machines, and the only debate was whether they would be evil or not. Stanley Kubrick was considered rather old-fashioned in assuming that the HAL-9000 computer in nditions . Their rIn fact, it took 50 years before computers that could genuinely be called ‘smart’ became more than lab toys, and that is because all those early successes were in what are now called Toy Domains. Take SHRDLU, for example, and its application to Blocks World . SHRDLU all react with each other, and with the products.In my view, almost all the OOL chemistry that I see is Toy Domain chemistry. It is making single types of biochemicals in a controlled laboratory setting using pure chemicals that might, just might, have been present in trace amounts in a complex mixture of thousands of other chemicals at OOL, under conditions that might have existed and might have persisted long enough, and then stopping the reaction at exactly the right time to maximize the yield of what you want solved in an unrealistic way. Only by a tiny, outside chance can lab reactions of specific reagents, even to give “messy” products, be part of a larger solution. The research does tell us something about chemistry. But it is not something that has much relevance to OOL, because if you carry out lab organic chemistry on anything approaching a plausible pre-biotic aqueous organic soup you never get life. You get tar [Of course OOL chemists understand that 99% pure reagents were not available at OOL. The hope is that by exploring what happens in “clean” chemistry you can gain insight into messier chemistry, and so edge towards more realistic scenarios. Indeed, there is a growing body of work on “messy chemistry”—doing lab chemistry with mixtures and accepting impure products as valid outputs ,46. Most get tar . Even ifnot start from pure chemicals? It is still controversial that there is any plausible route to make nucleotides in prebiotic conditions [of any sequence is ~5 × 10−10, and the yield of 15-mer or longer peptides with a pattern of amino acids that might form a pore is <2 × 10−15. . But it still starts from a pure starting material to make an impure product.Where do we go from here? Can we get hints how to move beyond this from the history of AI? One hint is sheer scale.outside extremely limited, restricted domains? In a famous paper [Sufficiently large changes of scale result in qualitative change. The failure of the Toy Domain applications of the 1960s and early 1970s was thought by some to sound the death knell for genuine machine intelligence. For example, could a computer understand natural language us paper , John Sebytes. I have been given 107 times that amount of memory in a USB flash drive as a free marketing giveaway. Now we understand that datasets bigger than the entire of digitized knowledge in 1980 and processors billions of times more capable can indeed execute what amounts to a Chinese Room translation, and use the resulting “understanding” to direct their behaviour. More, this combination of huge datasets and complex algorithms shows disturbingly powerful insights into our wants, needs and likely desires. Sheer power and parallelization has solved the problem.Thirty years on, we see the fallacies in Searle’s analogy. To work, the book would have to be of literally astronomical size to contain every possible sentence in Chinese, and the human be able to move at relativistic speeds to look anything up in it. It is so unrealistic as to be absurd. Since then, the scale of computation has changed by many orders of magnitude, and an equivalent of just such a look-up scheme has become possible. The onboard computers in the Apollo command/service module had a memory of 2 k dynamic memory (and 32 k of ROM). That is 2048  in the position of 19th century astronomers theorizing on why the Sun shines. Their theories were imaginative, thoughtful, authoritative, quantitative, and completely wrong  inability to define this in chemically testable terms is one on the major roadblocks in our understanding of the emergence of life that AL hardly mentions; how translation arises .not do is at least as important we what they do [There is also a lot of excitement about “systems chemistry” and “autocatalytic” systems, catalysed mainly by Stuart Kauffman . Kaufman they do . But thi they do ). Any su they do . We needAnd we hear every now and again about “New Physics” , a term And for this, last reason, grounding in the world of the real, Deamer’s vision is valuable. Read the book. Disagree with it, or with me, or both. Learn from it. And then go away and think.


Capacitive micromechanical resonators share electrodes with the same bias voltage, resulting in the occurrence of electrostatic coupling between intrinsic modes. Unlike the traditional mechanical coupling, the electrostatic coupling is determined by the structural electric potential energy, and generally, it only occurs when the coupling modes operate in nonlinear regions. However, previous electrostatic coupling studies mainly focus on the stiffness softening region, with little attention on the opposite stiffness hardening condition. This paper presents a study on the electrostatic modal coupling effect in the stiffness hardening region. A novel capacitive micromechanical resonator with different modal nonlinearities is designed and fabricated. It is demonstrated that activating a cavity mode can shift the fundamental resonance of the manipulated mode by nearly 90 times its mechanical bandwidth. Moreover, the frequency shifting direction is found to be related to the manipulated mode’s nonlinearity, while the frequency hopscotch is determined by the cavity mode’s nonlinearity. The electrostatic coupling has been proven to be an efficient and tunable dynamical coupling with great potential for tuning the frequency in a wide range. The modal coupling theory displayed in this paper is suitable for most capacitive resonators and can be used to improve the resonator’s performance. With the development of advanced lithography and micromachining processes, the sizes of micro-electro-mechanical-system (MEMS) resonators are constantly shrinking, expanding their applications in various fields such as RF filters, accelerometers, gyroscopes, pressure sensors, and so on ,5,6,7,8.According to different manifestations, the main nonlinearities in resonators are divided into two categories, the mechanical nonlinearity and the electrostatic nonlinearity ,15,16,17The mutual coupling and interactions between two distinct modes are typical representatives of the frontier research in the resonator’s mechanism and applications, which has been studied for decades . The appIn a capacitive micromechanical resonator, the electrostatic nonlinearity is common since its resonant structure is driven and detected by electrical methods. As a result, its modal coupling studies mainly focus on the condition where the coupled modes both have electrostatic nonlinearities . There iIn this paper, the modal coupling effect in a nonlinear micromechanical resonator is theoretically analyzed and associated with experimental results. A novel vacuum-packaged capacitive micromechanical resonator is designed and fabricated, whose different modes exhibit different nonlinearities, to analyze the modal coupling effect between different nonlinear modes. This paper is organized as follows. The basic structure of the capacitive resonator and controlling circuits are briefly introduced in T is 40 μm, length L is 3 mm, width W is 3 mm, the spindle azimuth angle of the oblique beam pθ is 88.5°, and the capacitance gap d0 is 2 μm. In order to reduce the air damping, the vacuum-packaging process is applied, maintaining the resonator in a vacuum of 0.1 Pa. A novel capacitive micromechanical resonator is specially designed and fabricated in this work. It is a tuning fork resonator consisting of two proof-masses, two anchors, one stress-released structure, and one oblique beam ,26. The The primary process of the resonator includes dry etching, wet etching, silicon-silicon bonding, and wafer-level vacuum packaging. Firstly, the electrode layer was manufactured on a silicon-on-insulator (SOI) wafer. The desired electrode shape was obtained under a mask layer by using the dry etching. Afterward, wet etching (machining the oblique beam) and dry etching methods were applied to fabricate the resonator’s sensitive structure on another SOI wafer, which had been bonded to the former one. Finally, a cap prepared with a getter was bonded to the structural wafer, and after the laser dicing, a single vacuum packaged resonator could be obtained. The detailed process is illustrated in The mode is an inherent vibrational characteristic of the structural system, and each mode has a specific natural frequency, damping ratio, and mode shape. As for the capacitive micromechanical resonator used in this work, its motion mainly includes the out-plane oscillation and the in-plane oscillation. This paper focuses on the resonator’s asymmetric torsion mode and symmetric bending mode, corresponding to its out-plane oscillation and in-plane oscillation, respectively. With the help of finite element simulation software, it is easy for us to get the information of the resonator’s different modes. The modal simulation results are displayed in Using the sweeping circuits, we can get the actual fundamental frequencies of the resonator’s different modes, shown in The electrodes are connected to external pads through the lead wire layer. As a result, it is possible to flexibly select electrodes for different needs. To carry out the dynamic modal coupling experiments, a Zurich lock-in amplifier (HF2LI) is used to produce the excitation signal and pump signal at the same time. Then the resonator’s response signal enters the lock-in amplifier for analysis after demodulation. The schematic diagram of controlling circuits is displayed in Previous researches demonstrated that the main nonlinearities in capacitive micromechanical resonators could be defined as the mechanical nonlinearity and the electrostatic nonlinearity . The mecI is the inertia moment of the resonator, c is the damping coefficient, M is the excitation torque, k0 is the inherent elastic coefficient, k1, k2, and k3 are the first order, the second order, and the third order nonlinear elastic coefficient, respectively. These nonlinear elastic coefficients are determined by the combination of the resonator’s mechanical and electrostatic properties. As for the capacitive micromechanical resonator used in this work, its second order nonlinear elastic coefficient is small enough to be ignored, which would be analyzed in the following part.Considering these nonlinearities, the simplified nonlinear dynamic model of the capacitive micromechanical resonator could be represented by the Duffing equation as shown below :(1)Iϕ¨+cUsing the multi-scale method , we can Here,κ, the resonator’s response will exhibit different nonlinear properties as shown in κ = 0), the response presents a typical Lorentzian shape. However, it is demonstrated that the relationship between the resonator’s amplitude and frequency is no longer a simple one-to-one correspondence in the nonlinear condition. When κ < 0, its response curve will deflect to the left, which is called the stiffness softening effect mainly caused by the electrostatic nonlinearity. By contrast, when κ > 0, this curve will deflect to the right, which is defined as the stiffness hardening effect induced by the mechanical nonlinearity. Actually, the electrostatic nonlinearity and mechanical nonlinearity coexist in a resonator, and the final form of the response depends on the dominant factor in these two nonlinearities.It is obvious that with the change of The specially designed resonator’s motion mainly includes the out-plane and in-plane oscillation, whose representative is the asymmetric torsion mode and symmetric bending mode, respectively. Therefore, the nonlinear characteristics of these two modes are analyzed in the following parts.The mechanical nonlinearity is mainly caused by the structure’s nonlinear elastic restoring force. This type of nonlinearity is derived from the geometric structure’s nonlinear deformation at large displacement . The reslF could be calculated as:E is the silicon’s Young’s modulus, S is the cross-section area of the beam, while L0 and L are the initial length of the beam and its length after deformation, respectively. Since the deformation is slight enough when compared with its length, the deformed beam can be approximated as a straight beam. As a result, the beam’s length after the bending deformation could be expressed as:y is the displacement of the beam’s midpoint. Its mechanical tension yF could be calculated as:After the bending deformation, the beam’s tension L0/4 from the anchor point, and the bending movement’s turning center is L0/8 from the anchor point. Therefore, the bending arm yL = 3L0/8 and the bending angle yϕ due to the deformation is:In this resonator, sensitive masses are mounted at Finally, we can get the expression of the additional mechanical moment:As a result, the mechanical nonlinear elastic coefficients of the bending oscillation due to its structural deformation can be expresses as:The electrostatic nonlinearity in a capacitive resonator is mainly derived from high-order nonlinear electrostatic forces generated by large displacements . This paThis device uses a differential excitation method so its electrostatic force could be calculated as:+U = d + UacosUωt, − = UdU − acosUωt, A is the capacitance area, y is the oscillation displacement, ε0 is the vacuum dielectric constant, rε is the free space’s permittivity, and d0 is the initial capacitance gap. Similarly, using the Taylor expansion method, Equation (10) could be rewritten as: Here, y = tLtϕ, where tL is the horizontal distance from the electrode’s center to the oblique beam. Therefore, when the number of excitation electrode couples is 2, the moment caused by the electrostatic force could be calculated as:Considering the resonator’s torsion motion, the relationship between its oscillation displacement and the torsion angle is aU << dU in the experiments, ignoring those little AC items, the resonator’s torsional modal electrostatic nonlinear elastic coefficients can be expressed as:Since y = bLbcosθpϕ, where bL is the horizontal distance from the electrode’s center to the oblique beam. Therefore, when the number of driving electrodes couples is 4, the moment caused by the electrostatic force could be calculated as:Considering its bending motion, there is Similarly, its bending modal electrostatic nonlinear elastic coefficients can be expressed as:t0k of the resonator’s asymmetric torsion mode can be obtained through the mechanical analysis [G is silicon’s shear modulus, tI, β, w0, 0,h and L0 is the oblique beam’s inertia polar moment, torsion coefficient, width, height, and length, respectively. The nonlinear elastic coefficients of the resonator’s asymmetric torsion mode could be expressed as:The resonator’s asymmetric torsion mode is shown in analysis :(16)kt0=Based on its actual structure and experimental settings, we can get the parameter values needed for theoretical calculation Equation (2), as shown in Therefore, the resonator’s asymmetric torsion modal A-F curves with different AC voltages could be simulated as shown in b0k can be obtained through the mechanical analysis [wI, w0, h0, and L0 is the oblique beam’s main inertia moment, width, height, and length, respectively. Its nonlinear elastic coefficients could be expressed as:The resonator’s symmetric bending mode is shown in analysis :(18)kb0=Based on its actual structure and experimental settings, we can get the parameter values needed for theoretical calculation Equation (2), as shown in Therefore, the resonator’s symmetric bending modal A–F curves with different AC voltages could be simulated as shown in Obviously, through the special structural design, the resonator’s asymmetric torsion mode and symmetric bending mode have opposite nonlinearities, making it an ideal experimental device for analyzing the electrostatic modal coupling effect in the stiffness hardening region.It has been proved in previous researches that capacitors can achieve the dispersive electrostatic modal coupling effect . The capjk, jI, and Φj  are the resonator’s inherent stiffness, inertia moment, and oscillational angle, respectively. ∆V is the bias voltage on shared electrodes, while a and b are linear motion coefficients. Using the Lagrange method, the coupled system’s dynamic equations could be expressed as:In order to avoid the pull-in effect, the resonator’s vibrational angles are limited in a small range. The change of the capacitive area can be ignored. As a result, when two modes are excited together, the system’s kinetic and potential energy could be expressed as:Introduce damping terms and expand nonlinear terms, Equation (21) can be rewritten as:Based on the multi-scale method , the relBased on its actual structure and experimental settings, we can get the parameter values needed for theoretical calculation Equation (23), as shown in As a result, the electrostatic modal coupling effect could be simulated by numerically solving Equation (23) and the simulation result is displayed in Throughout the experiments, the device was placed in a temperature-controlled chamber and maintained at a constant temperature of 303.15 K. Before experimental tests, the resonator pre-operated for 2 h under the above constant temperature condition, and then data started to be collected. In this way, start-up errors and temperature drift errors can be greatly reduced.In these experiments, a stable 6.5 V DC voltage and different AC excitation signals produced by the lock-in amplifier are applied on these excitation electrodes as shown in As shown in In the modal coupling experiments, this novel resonator’s asymmetric torsion mode and symmetric bending mode are simultaneously actuated by the probe and pump electrodes, respectively. The asymmetric torsion mode is excited in its stiffness softening region with an AC excitation voltage of 50 mV, while the symmetric bending mode is in its stiffness hardening condition with a pump signal of 250 mV. In this case, the resonator’s manipulated mode and cavity mode are excited in different nonlinear conditions. The manipulated mode’s responses at different pump frequencies are recorded, and a typical dispersive modal coupling effect is observed in Obviously, with the increment of the pump frequencies, the asymmetric torsion mode’s fundamental frequency shifts to a low frequency region, which is consistent with the theoretical simulation result. The frequency shift of the manipulated mode is about 375.11 Hz, nearly 90 times its mechanical bandwidth 4.2 Hz. As a result, it has been proved from the experiments and analysis that the electrostatic modal coupling effect is a good method to tune the frequency difference between two coupled modes. Moreover, the frequency hopscotch of the manipulated mode also appears in the latter stage consistent with the condition when the cavity mode shows a mechanical nonlinearity.It is obvious that when the related parameters are the same, the results of theoretical simulation and experimental tests are consistent, which proves the correctness of theoretical models.According to the electrostatic coupling theory, it is reasonable that the manipulated mode’s frequency will change with the cavity pump mode’s motion . The cavFurthermore, it should be noted that the manipulated mode’s frequency hopscotch is quite different from the conventional electrostatic modal coupling frequency hopscotch. In the conventional electrostatic modal coupling, the electrostatic nonlinearity dominates in these coupled modes. When these electrostatic nonlinear modes couples, the manipulated mode’s frequency hopscotch appears in the initial region as shown in Figure 4d from Reference . Howeverjmaxσ:This frequency shifting difference could also be explained theoretically. Based on Equation (23), it is easy to get the maximum frequency shift of the coupled modes Λ2, Π2 and Λ3, Π3. These key parameters are exactly the reflection of coupled modes’ nonlinear elastic coefficients as shown in Equation (24), which means that the frequency shift direction of each mode is dominated by its own nonlinearity. When the mode is dominated by the electrostatic nonlinearity, its frequency will shift downward, while in the mechanical nonlinear condition, it will shift upward.It can be obtained that frequency shift directions of coupled modes are determined by As for the frequency hopscotch of the manipulated mode, it depends on the nonlinearity of the cavity mode. When the cavity mode is a mechanical nonlinear mode, its fundamental frequency will shift to a higher region. During the pumping process, the manipulated mode will encounter the resonant frequency of the cavity mode in the latter stage so that its frequency hopscotch appears in the latter stage. In this case, the manipulated mode’s frequency will slightly decrease with the increment of the pump signal at first. Then the frequency hopscotch appears and the manipulated mode’s frequency jumps back to its initial value in the latter stage as shown in It is demonstrated that the frequency shifts of modes are closely related to the state of the manipulated mode and the cavity mode, which determined the shift direction and frequency hopscotch, respectively. This electrostatic modal coupling model is suitable for the most capacitive micromechanical resonators, especially when the coupled modes have different types of nonlinearities.The modal coupling effect in a novel nonlinear micromechanical resonator is studied in this paper. To analyze the electrostatic modal coupling effect with different nonlinear coupled modes, a novel tuning fork resonator is specially designed and fabricated. In this capacitive micromechanical resonator, due to its unique structure size and excitation method, its main operating modes show the mechanical nonlinearity and the electrostatic nonlinearity, respectively.It is worth noting that due to the existence of shared electrodes, the resonator’s intrinsic modes are no longer independent of each other, but coupled together. Therefore, the oscillation of any mode will modulate the other modes’ states. The displacement of the cavity pump mode will cause an electrostatic negative stiffness in the manipulated mode, causing its frequency shifting. Meanwhile, the shift direction is determined by the sign of the manipulated mode’s nonlinear coefficient. It has been demonstrated that the frequency shift range is normally much larger than its mechanical bandwidth, indicating that it could be used to tune the frequency in a wide range.Moreover, this paper also compares the effect of different nonlinear cavity modes on the frequency shifting. It has been found that the nonlinearity of the cavity mode dominates the location of the manipulated mode’s frequency hopscotch. When the cavity mode is a mechanical nonlinear mode, during the pumping process, the manipulated mode will encounter its frequency hopscotch in the latter stage. On the contrary, when the cavity mode is an electrostatic nonlinear mode, the manipulated mode’s frequency hopscotch will appear in the initial stage.The dispersive modal coupling effect is a product of the coherent phonon manipulation based on the electrostatic coupling, and it has great potential in enhancing the sensor performance. It has been proven that it is a good method to tune the frequency difference between two coupled modes in a wide range. Further, this electrostatic modal coupling model presented in this work is suitable for most capacitive micromechanical resonators.